111

11111

1

,311 11

111

I

United States

Environmental Protection

Agency

Office of Water

Regulations and Standards

Criteria and Standards Division

Washington DC 20460

IEPA ATTACHMENT No,

EE

EPA 440/5-80-071

October 1980

SEPA Ambient

Water Quality

Criteria for

Silver

LIBRARY

Environmental Protection Agency

State of Illinois

Springfield, Illinois

---

AMBIENT WATER QUALITY CRITERIA FOR

SILVER

Prepared By

U.S. ENVIRONMENTAL PROTECTION AGENCY

Office of Water Regulations and Standards

Criteria and Standards Division

Washington, D.C.

Office of Research and Development

Environmental Criteria and Assessment Office

Cincinnati, Ohio

Carcinogen Assessment Group

Washington, D.C.

Environmental Research Laboratories

Corvalis, Oregon

Duluth, Minnesota

Gulf Breeze, Florida

Narragansett, Rhode Island

---

DISCLAIMER

This report has been reviewed by the Environmental Criteria and

Assessment Office, U.S. Environmental Protection Agency, and approved

for publication. Mention of trade names or commercial products does not

constitute endorsement or recommendation for use.

AVAILABILITY NOTICE

This document is available to the public through the National

Technical Information Service, (NTIS), Springfield, Virginia 22161.

---

FOREWORD

Section 304 (a)(1) of the Clean Water Act of 1977 (P.L. 95-217),

requires the Administrator of the Environmental Protection Agency to

publish criteria for water quality accurately reflecting the latest

scientifi

c

knowledge on the kind and extent of all identifiable effects

on health and welfare which may be expected from the presence of

pollutants in any body of water, including ground water. Proposed water

quality criteria for the 65 toxic pollutants listed under section 307

(a)(1) of the Clean Water Act were developed and a notice of their

availability

was published for public comment on March 15, 1979 (44 FR

15926), July 25, 1979 (44 FR 43660), and October 1, 1979 (44 FR 56628).

This document is a revision of those proposed criteria based upon a

consideration of comments received from other Federal Agencies, State

agencies, special interest groups, and individual scientists. The

criteria contained in this document replace any previously published EPA

criteria for the 65 pollutants. This criterion document is also

published in satisifaction of paragraph 11 of the Settlement Agreement

in Natural Resources Defense Council, et. al. vs. Train, 8 ERC 2120

(D.D.C. 19/6), modified, 12 ERC-1833 (D.D.C.-1979).

The term "water quality criteria" is used in two sections of the

Clean Water Act, section 304 (a)(1) and section 303 (c)(2). The term has

a different program impact in each section. In section 304, the term

represents a non-regulatory, scientific assessment of ecological ef-

fects. The criteria'presented in this publication are such scientific

assessments. Such water quality criteria associated with specific

stream uses when adopted as State water quality standards under section

303 become enforceable maximum acceptable levels of a pollutant in

ambient waters. The water quality criteria adopted in the State water

quality standards could have the same numerical limits as the criteria

developed under section 304. However, in many situations States may want

to adjust water quality criteria developed under section 304 to reflect

local environmental conditions and human exposure patterns before

incorporation into water quality standards. It is not until their

adoption as part of the State water quality standards that the criteria

become regulatory.

Guidelines to assist the States in the modification of criteria

presented in this document, in the development of water quality

standards, and in other water-related programs of this Agency, are being

developed

by EPA.

STEVEN SCHATZOW

Deputy Assistant Administrator

Office of Water Regulations and Standards

i

ii

---

ACKNOWLEDGEMENTS

Aquatic Life Toxicology

William A. Brungs, ERL-Narragansett

?David

J. Hansen, ERL-Gulf Breeze

U.S. Environmental Protection Agency

?U.S.

Environmental Protection Agency

Mammalian Toxicology and Human Health Effects

Bonnie Carson (author)

Midwest Research Institute

Christopher DeRosa (doc. mgr.), ECAO-Cin

U.S. Enviromental Protection Agency

Bonnie Smith (doc. mgr.), ECAO-Cin

U.S. Environmental Protection Agency

Ernest Foulkes

University of Cincinnati

Dinko Kello

Institute for Medical Research

Edward W. Lawless

Midwest Research Institute

Jerry F. Stara, ECAO-Cin

U.S. Environmental Protection Agency

Robert M. Bruce, ECAO-RTP

U.S. Environmental Protection Agency

Richard Bull, HERL

U.S. Environmental Protection Agency

Patrick Durkin

Syracuse Research Corporation

Alfred Garvin

University of Cincinnati

Terri Laird, ECAO-Cin

U.S. Environmental Protection Agency

Steven D. Lutkenhoff, ECAO-Cin

U.S. Environmental Protection Agency

Technical Support Services Staff: D.J. Reisman, M.A. Garlough, B.L. Zwayer,

P.A. Daunt, K.S. Edwards, T.A. Scandura, A.T. Pressley, C.A. Cooper,

M.M. Denessen.

Clerical Staff: C.A. Haynes, S.J. Faehr, L.A. Wade, D. Jones, B.J. Bordicks,

B.J. Quesnell,

P.

Gray, B. Gardiner, R. Swantack.

i

v

---

TABLE OF CONTENTS

Criteria Summary

Introduction

Page

A-1

Aquatic Life Toxicology

8-1

Introduction

Effects

B-3

Acute Toxicity

B-3

Chronic Toxicity

8-6

Plant Effects

B-10

Residues

B-11

Miscellaneous

8-11

Summary

?

.

B-12

Criteria

8-13

References

B-34

Mammalian Toxicology and Human Health Effects

Introduction

C-1

Exposure

C-1

Ingestion from Water

C-1

Ingestion from Food

C-17

Inhalation

C-21

Dermal

?

'

C-29

Pharmacokinetics

C-33

Absorption

C-33

Distribution

C-40

Metabolism

C-52

Excretion

C-56

Effects

C-68

Acute, Subacute and Chronic Toxicity

C-68

Synergism and/or Antagonism

C 94

Teratogenicity

C-102

Mutagenicity

C-104

Carcinogenicity

C-106

Criterion Formulation

C-116

Existing Guidelines and Standards

C-116

Current Levels of Exposure

C-119

Special Groups at Risk

C-121

Basis and Derivation of Criterion

C-122

References

C-129

---

CRITERIA DOCUMENT

SILVER

CRITERIA

Aquatic Life

For freshwater aquatic life the concentration (in ug/l) of total

recoverable silver should not exceed the numerical value given by

e

(1.72[1n(hardness)]-6.52) at any time. For example, at hardnesses of 50,

100, and 200 mg/1 as CaCO

3

, the concentration of total recoverable silver

should not exceed 1.2, 4.1, and 13 ug/1, respectively, at any time. The

available data indicate that chronic toxicity to freshwater aquatic life may

occur at concentrations as low as 0.12 ug/l.

For saltwater aquatic life the concentration of total recoverable silver

should not exceed 2.3 ug/1 at any time. No data are available concerning

the chronic toxicity of silver to sensitive saltwater aquatic life.

Human Health

The ambient water quality

criterion for silver is recommended to be

identical to the existing water standard which is 50 ug/l. Analysis of the

toxic effects data resulted in a calculated level which is protective of

human health against the ingestion of contaminated water and contaminated

aquatic

organisms. The calculated value is comparable to the present stan-

dard. For this reason a selective criterion based on exposure solely from

consumption of 6.5 grams of aquatic organisms was not derived.

v

i

---

INTRODUCTION

Silver is a white, ductile metal occurring naturally in the pure form

and in ores. Principal uses of silver are in photographic materials, elec-

troplating, as a conductor, in dental alloys, solder and brazing alloys,

paints, jewelry, silverware, coinage, and mirror production. Silver is of

some use as an antibacterial agent and has been shown to be bactericidal

even in concentrations that are not great enough to precipitate proteins;

the assumption is that silver is capable of interfering with essential meta-

bolic processes in the bacterial cell (Goodman and Gilman, 1975).

Silver can exist in two valence states, Ag+ and Ag++. It has an atomic

weight of 107.87. Solubilities of a few common silver salts in water are:

AgC1, 1,930 ug/1; AgNO3

, 2.5 x 109

ug/1; and AgI, 30 ug/1 (Windholz,

1976).?

Silver occurs primarily in the form of the sulfide (argentite

Ag

2S)

or intimately associated with other metal sulfides, especially those

of lead and copper.?

Other common silver minerals include cerargyrite

(AgC1),?

proustite

?

(3AgS As2S3),

?

pyragyrite

?

(3Ag2S Sb2S3),?

stepha-

nite (5Ag2S Sb2S3

) and native metallic silver.

?

Most lead and copper

ores are argentiferous, though there are important exceptions. Recovery of

silver and gold from these ores constitutes an important part of their

metallurgical treatment.

Silver is also commonly associated in nature with gold. Not only does

gold occur with silver in copper and lead ores, but native metallic gold

usually contains silver. Gold and silver are mutually soluble in each other

in all proportions in the metallic state.

Silver is usually found in extremely low concentrations in the aquatic

environment, due both to its low crustal abundance and the effectiveness of

A-1

---

controls on its mobility in water. In a study of 10 U.S. rivers, Kharkar,

et al. (1968) detected silver in concentrations ranging from 0.092 to 0.55

ug/l. Hem (1970) cites studies of public drinking water supplies and river

waters which report median concentrations of 0.23 and 0.09 pg/l, respec-

tively. The geochemistry of silver has been extensively reviewed by Boyle

(1968).

Sorption and precipitation processes are effective in reducing the con-

centration of dissolved silver and result in higher concentrations in the

bed sediments than in the overlying waters. Sorption by manganese dioxide

and precipitation with halides are probably the dominant controls on the

mobility of silver in the aquatic environment. Some silver is also bioaccu-

mulated, and the remainder is transported in solution to the oceans (U.S.

EPA, 1979).

A

---

REFERENCES

Boyle, R.W. 1968. The geochemistry of silver and its deposits. Geol. Sur-

vey of Canada, Bull. 160, Ottawa, Canada.

Goodman, L.S. and A. Gilman (eds.)

?

1975. The Pharmacological Basis of

Therapeutics. 5th ed. MacMillan Publishing Co., Inc., New York.

Hem, J.D. 1970. Study and interpretation of the chemical characteristics

of natural waters. U.S. Geol. Survey Paper 1473, Washington, D.C. p. 202.

Kharkar, D.P., et al. 1968. Stream supply of dissolved silver, molybdenum,

antimony, selenium, chromium, cobalt, rabidium and cesium to the oceans.

Geochim. Cosmochim. Acta. 32: 285.

U.S. EPA. 1979. Water-related environmental fate of 129 priority pollut-

ants. EPA 68-01-3852. U.S. Environ. Prot. Agency, Washington, D.C.

Windholz, M. (ed.) 1976. The Merck Index. 9th ed. Merck and Co., Inc.,

Rahway, New Jersey.

A-3

---

Aquatic Life

Toxicology*

INTRODUCTION

Silver exhibits oxidation states of 0, +1, +2, and +3, but only

the o

and +1 states occur to any extent in the environment. In natural water, the

monovalent species is the form of environmental concern. In water, silver

may exist as simple hydrated monovalent ions completely dissociated from an-

ions that at one time could have been part of its crystalline salt lattice.

In addition, monovalent silver ions may exist in various degrees of associa-

tion with a large number of inorganic ions, such as sulfate, bicarbonate,

and nitrate, to form numerous compounds with a range of solubilities and po-

tentials for hydrolysis or other reactions. Hem (1970) speculates that

where chloride concentrations exceed 35 mg/1, silver chloride may exert a

major control on solubility of silver.

Sorption appears to be the dominant process leading to partitioning into

sediments. It appears that manganese dioxide, ferric compounds, and clay

minerals all have some degree of adsorptive affinity for silver and are in-

volved in its deposition into sediments (Kharkar, et al. 1968). Dyck (1968)

observed that sorption of silver was strongly dependent on pH. In addition,

silver may be freed from these compounds

by

reducing conditions in the sedi-

mentary layer and thus may be reduced to metallic silver or may combine with

reduced sulfur to form the extremely insoluble silver sulfide. Finally sil-

ver may exist as metal—organic complexes or may be adsorbed by organic ma-

terials in natural waters.

*The reader is referred to the Guidelines for Deriving Water Quality

Criteria for the Protection of Aquatic Life and Its Uses in order to better

understand the following discussion and recommendation. The following

tables contain the appropriate data that were found in the literature, and

at the bottom of each table are calculations for deriving various measures

of toxicity as described in the Guidelines.

B-1

---

Silver is one of the most toxic metals to freshwater aquatic life. Most

of the toxicity studies have been conducted with silver nitrate, which is an

excellent source of free soluble silver ions. ?

Insoluble silver salts are

much less toxic than silver nitrate. Chambers and Proctor (1960) found that

the germicidal action of silver in distilled water was

, related to the con-

centration of silver ions rather than the physical nature of the silver from

which the ions were originally derived.

Limited information is available concerning the relationship of various

forms of silver and toxicity to aquatic animals. Data indicate that the

acute toxicity of silver to freshwater fishes and Daphnia magna is related

to water hardness, with silver being more toxic in soft water. The acute

toxicity of silver also is related to chloride concentration, but the data

base for this relationship is insufficient to develop criteria on the basis

of chloride concentration. The data base for saltwater organisms is insuf-

ficient to determine the importance of salinity, temperature, and other

water quality factors on the toxicity of silver.

Of the analytical measurements currently available, a water quality cri-

terion for silver is probably best stated in terms of total recoverable sil-

ver, because of the variety of forms of silver that exist in bodies of water

and the various chemical and toxicological properties of these forms. The

forms of silver that are commonly found in bodies of water and are not mea-

sured by the total recoverable procedure, such as the silver that is in

minerals, clays, and sand, probably are forms that are less toxic to aquatic

life and probably will not be converted to the more toxic forms very readily

under natural conditions. On the other hand, forms of silver that are com-

monly found in bodies of water and are measured by the total recoverable

procedure, such as the free ion and the hydroxide, carbonate, and sulfate

8-2

---

salts, probably are forms that are more toxic to aquatic life or can be con-

verted to the more toxic forms under natural conditions. Because the cri-

terion is derived on the basis of tests conducted on soluble inorganic salts

of silver, the total silver and total recoverable silver concentrations in

the tests will probably be about the same, and a variety of analytical pro-

cedures will produce about the same results. Except as noted, all concen-

trations reported herein are expected to be essentially equivalent to total

recoverable silver concentrations. All concentrations are expressed as sil-

ver, not as the compound.

EFFECTS

Acute Toxicity

The data base concerning acute toxicity of silver to freshwater organ-

isms includes 82 acute values for 10 species from nine different taxonomic

families (Table 1). The invertebrate species include a planktonic crusta-

cean, a benthic crustacean that is a detritivor, and a benthic insect among

others, whereas the fish species include a salmonid and five nonsalmonid

species.

For the four invertebrate species, the acute values for silver range

from 0.25 ug/1 for Daphnia magna to 4,500 ug/1 for the scud Gammarus pseudo-

limnaeus, both of which were tested in Lake Superior water (Table 1).

Most of the acute values for freshwater fish are for the rainbow trout

and fathead minnow (Table 1). The acute values in flow-through tests ranged

from 3.9 ug/1 for the fathead minnow in soft water to 280 ug/1 for rainbow

trout in hard water. This range of acute values for six fish species was

much less than the range of acute values for four invertebrate species.

Chapman, et al. (Manuscript) examined the acute toxicity of silver to

Daphnia macula with and without food being added to the test solutions. The

8-3

---

acute value with food was 9.5 ug/1 (Table 6).

?

In a side-by-side test

conducted with no food added (Table 1), the acute value was 0.25 ug/l.

Lemke (Manuscript) also reported the results of side-by-side tests to com-

pare the effect of food on acute toxicity. The result with added food was

43 u9/1 (Table 6), and with no added food the results were 8.4 and 15 ug/1

(Table 1). Because this effect is observed with some metals, but not with

others, it appears that this daphnid food, or some component of it, greatly

decreases the acute toxicity of silver.

The results of a study (EG&G Bionomics, 1979) designed to evaluate the

relative toxicity of different forms of silver to the fathead minnow are

given in Tables 1 and 6. Flow-through tests using measured total silver and

free silver (pAg) concentrations were conducted.?

Silver nitrate with a

96-hour LC

50

value of 16 ug/1 (Table 1) was the most toxic silver COM-

pound. The 96-hour LC50

values for silver were 510 and 5,600 pg/1 when

the concentration of chloride was increased to 500 and 2,000 mg/1, respec-

tively (Table 6). These test solutions were clear, indicating that silver

was apparently present as a soluble chloride complex.

?

Silver thiosulfate

and both forms of silver sulfide were even less toxic.

The results of a round-robin test in which six laboratories each con-

ducted duplicate static tests with Daphnia magna and duplicate static and

flow-through tests with rainbow trout and fathead minnows (Lemke, Manu-

script) are given

.

in Table 1. The results of all except one test, were

based on measured concentrations. Each laboratory reported that for the

fathead minnow and rainbow trout the results of the flow-through tests were

lower than the results of the static tests. The hardness of the water used

in each laboratory was available, and so a least-squares regression was per-

formed on the natural logarithms of the acute values (the flow-through

B-4

---

values for the fish) on the natural logarithms of hardness. The resulting

slopes were 2.29, 1.65, and 1.63 for Daphnia magna, rainbow trout, and fat-

head minnow, respectively, and all were statistically significant (p.0.01).

The concentrations of chloride were 1.2, 32, 8, 11, 13, and 1 mg/1 in the

waters whose hardnesses were 48, 255, 54, 46, 38, and 75 mg/1, respectively.

The regressions on chloride concentrations were not statistically signifi-

cant (p=0.05).

Other data, however, do not show this amount of effect of hardness on

the acute toxicity of silver. Goettl and Davies (1978) tested the acute

toxicity of silver to the fathead minnow, speckled dace, and mottled sculpin

in both soft and hard water. In addition, Davies, et al. (1978) tested the

rainbow trout in soft and hard water. These tests produced slopes of 0.10,

0.50, 0.46, and 0.26, respectively. The last slope is not statistically

significant (p.0.05), but the significance of the first three cannot be

tested because only two points are available.

The apparent lack of effect of chloride is surprising, although the

range of concentrations may be too low. The contradictory evidence con-

cerning the effect of hardness on acute toxicity is also surprising. A com-

parison of all the available data concerning the acute toxicity of silver to

both fathead minnows and rainbow trout suggests the possibility that silver

was unusually toxic in the hard water used by Goettl and Davies (1978) and

Davies, et al. (1978). Therefore, these results were not used in describing

the effect of hardness on the acute toxicity of silver. For the remaining

data, a least—squares regression of the natural logarithms of the acute val-

ues on the natural logarithms of hardness produced slopes of 2.35, 1.30, and

1.50, for Daphnia magna, rainbow trout, and fathead minnows, respectively.

All three slopes were statistically significant (p.0.01). If the data for

8-5

---

hard water from Goettl and Davies (1978) and Davies, et al. (1978) are used,

the slopes for rainbow trout and fathead minnow change from 1.30 and 1.50 to

1.00 and 1.14, respectively.

The arithmetic mean slope (1.72) was used with the geometric mean toxic-

ity value and hardness for each species to obtain a logarithmic intercept

for each species, but again the data obtained in hard water by Goettl and

Davies (1978) and Davies, et al. (1978) were not used. The species mean

acute intercept, calculated as the exponential of the logarithmic intercept,

was used to rank the relative sensitivities of the species (Table 3). A

freshwater Final Acute Intercept of 0.00147

Ng/1

was obtained for silver

using the species mean acute intercepts listed in Table 3 and the calcula-

tion procedures described in the Guidelines. Thus the Final Acute Equation

is e(1-72 [1n(hardness)]-6.52).

For saltwater animals, cute toxicity data are available for five fish

and five invertebrate species. dishes were both the most sensitive and most

resistant species tested (Table 3), but invertebrate species as a group were

generally more sensitive to silver than were the fish. Toxicity values

ranged from 4.7 Ng/1 for the summer flounder to 1,400 Ng/1 for the sheeps-

head minnow. The Saltwater Final Acute Value for silver, derived from the

species mean acute values listed in Table 3 using the calculation procedures

described in the Guidelines, is 2.3 pg/l.

Chronic Toxicity

The results of Daphnia magna renewal life-cycle tests are given in

Table 2.?

These chronic tests were conducted as part of a round-robin

testing program, similar to that discussed in Lemke (Manuscript), to evalu-

ate methods for acute and chronic toxicity tests using Daphnia magna

(Nebeker, et al. Manuscript b). ?

In contrast to the results of the acute

B-6

---

tests, no relationship could be found between hardness and chronic

toxicity. Three of the chronic values (2.6, 13, and 5.2 ug/l) are from the

laboratory which reported acute values of 0.6 and 1.1 ug/1. In addition, a

third acute in the same laboratory produced an acute value of 0.25 ug/1

(Nebeker, et al. Manuscript a). The chronic values of 15 and 29 ug/1 were

from the same laboratory as the acute values of 15 and 8.4 ug/1, whereas the

chronic value of 5.2 ug/1 corresponds to the acute value of 0.64 ugh'. In

each laboratory the average acute value for silver was lower than the aver-

age chronic value, probably because food was added to the test solutions in

the chronic test, but not in the acute tests.

Special acute tests with Daphnia magna were conducted in two laborator-

ies by adding food to the test solution as is done in the chronic test. In

one laboratory the acute values were 8.4 and 15 ug/1 without food (Table 1)

and 43 ug/1 with food (Table 6). The comparable chronic values were 15 and

29 ug/l, which results in an acute—chronic ratio of less than 1.0 using the

acute without food and 2.0 using the acute with food (Table 2).

?

In the

second laboratory in side—by—side tests, the acute value was 0.25 ug/1 with-

.

out food (Table 1) and 9.5 ug/1 with food (Table 6). Because of the varia-

tion in hardness, and probably other water q uality characteristics, and the

results of acute and chronic tests in this laboratory, it seems inappropri-

ate to calculate an acute—chronic ratio for Daphnia magma from these data.

Davies, et al. (1978) conducted an 18—month study to evaluate the ef-

fects of silver nitrate on survival and growth of rainbow trout (Table 2).

The exposure was initiated with eyed embryos which hatched after 26 days.

Premature hatching occurred in silver concentrations of 0.69, 0.34, and 0.17

ughl. After a 2—month exposure, the length of fish exposed to these three

high test concentrations was significantly (p=0.05) reduced. However, after

B-7

---

three and one-half months of exposure only the length of the fish in the

high concentration was significantly (p.0.05) less than the length of con-

trol fish. At the termination of the exposure, survival of fish exposed to

0.09 ug/1 was similar to the 79.9 percent survival of control fish. Mortal-

ity of fish exposed to 0.17 and 0.34 ug/1 was 17.2 and 36.6 percent greater,

respectively, than mortality of control fish. The results of this chronic

test and the comparable acute tests produced an acute-chronic ratio of 54

for silver and rainbow trout.

Davies and Goettl (1978) also investigated the effects of silver iodide

on survival and growth of rainbow trout (Table 6). One toxicity test was

initiated with eyed embryos and lasted for 13 months. These embryos hatched

in eight days, and swim-up was completed in 17 days. Survival through swim-

up was similar in all silver concentrations and ranged from 95.3 to 91.5

percent. Control mortality was not reported because of initial overcrowding

of control tank. Mortality of post swim-up fry was 3.2 percent for the fish

exposed to 0.03 ug/1 and was above 18 percent for concentrations of 0.06

ug/1 and higher. At the termination of the study the mean length of fish in

all silver concentrations was not significantly (p=0.05) different from the

mean length of control fish. Earlier growth measurements were not reported.

Another toxicity test with silver iodide was initiated with green embry-

os, and the exposure was for 10 months (Table 6). Hatching was completed

after seven weeks and swim-up was completed in 12 weeks. At this time sur-

vival of embryos and sac fry at all test concentrations was similar to sur-

vival of control embryos and sac fry. However, survival after swim-up was

only 73.2 percent in the high concentration of 0.40 ug/l. Survival of fish

in silver concentrations of 0.18 ug/1 and lower ranged from 96.4 to 98 per-

cent and was similar to the control fish survival of 97.6 percent. Growth

B-8

---

of control fish and fish exposed to silver was not significantly different

(

3=0.05)

after 8 and 10 months.

?

Earlier growth measurements were not

reported. The difference between the results of the two chronic tests on

silver iodide may have been due to embryonic acclimation to silver with the

longer exposure of the green embryos (Davies and Giettl, 1978). The dif-

ference may also have been just experimental variation.

The chronic values from these three chronic toxicity studies with rain-

bow trout using a similar dilution water and measured concentrations ranged

from 0.04 to 0.27 ug/l. Two of the three tests were started with eyed em-

bryos, and both of these chronic values were lower than the chronic value

from the test in which fertilized embryos were placed immediately into the

exposure system. The length of exposure of the embryos to silver nitrate

was intermediate between the length of exposure of embryos in the two silver

iodide tests, and the chronic value in the silver nitrate test was interme-

diate between the two chronic values of the silver iodide tests.

Nebeker, et al. (Manuscript c), conducted an early life stage test for

90 days using rainbow (steelhead) trout. The chronic value of 12 ug/1 was

greater than the 96—hour LC

50

value (Table 1) that Nebeker, et al. (1980)

reported for flow—through tests using rainbow trout.?

In addition, this

chronic value was two orders of magnitude greater than the chronic values

reported by Davies, et al. (1978) and Davies and Goettl (1978) for rainbow

trout. No acute—chronic ratio was calculated from the results of this early

life stage test.

A chronic toxicity value of 18 ug/1 for the saltwater mysid shrimp was

determined (Table 2) in a flow—through, life—cycle test (Lussier and Gen-

tile, 1980). In this experiment, groups of 20 juvenile shrimp were reared

in each of five silver concentrations for 58 days at 20°C and 30 g/kg salin-

8-9

---

ity. Responses examined included time of appearance of first brood, time of

first spawn, mean brood size (larvae/female), growth of larvae, and survival

of first filial generation. No spawning occurred at 103 pg/l, and time of

spawning was delayed to seven days at 33.3 pg/l. Brood size was statistic-

ally (p<0.05) smaller at 33.3 pg/1 as compared to controls. Larval survival

was unimpaired and was at least 95 percent in all treatments, and larval

growth was not retarded at any test concentration. The highest concentra-

tion of silver tested having no statistically significant effect on growth,

reproduction, or survival was 10 pg/l. The 96-hour LC

50

for this species

in the same study was 250 pg/l, and the acute-chronic ratio for this species

was 14.

Because of the variation in the results of chronic tests with rainbow

trout and the problem with determining an acute-chronic ratio for Daphnia

magna, neither a Final Acute-Chronic Ratio nor a Freshwater or Saltwater

Final Chronic Value can be determined for silver.

Plant Effects

Data on the toxicity of silver to 13 freshwater plant species are listed

in Table 4. The adverse effect concentrations range from 30 to 7,500 pg/l.

Even though these tests were conducted in various growth media and different

effects were measured, it appears that the adverse effects of silver on

plants are unlikely at concentrations which will not adversely affect fresh-

water animals.

Fitzgerald (1967) studied the effect of halides on the toxicity

of sil-

ver. He compared the algistatic activity

of

silver nitrate on Chlorella u-

renoidosa in the presence and absence of 12 mg/1 of sodium chloride, sodium

bromide, or sodium iodide.?

The results indicated that sodium chloride

caused

a

slight but consistent decrease in the toxicity of silver nitrate.

Sodium iodide caused the greatest decrease in toxicity of silver nitrate.

B -10

---

This decrease in toxicity was related to the solubility of the silver

halide. The least soluble silver halide, silver iodide, was the least tox-

ic.

?

He also reported that both live and dead algae detoxified silver

nitrate.

Stokes, et al. (1973) found that 30 pg/1 of silver inhibited the growth

of Chlorella vulgaris.

?

In addition, two species of green algae isolated

from small lakes which had high concentrations of heavy metals, especially

copper and nickel, had higher tolerances to silver than algae of the same

genus from the laboratory.

Information on the sensitivity of saltwater plants to silver is limited

to the results of one test showing a 50 percent reduction in chlorophyll a

production at 170 pg/1 and a 50 percent decrease in cell number at 130 Ng/1

(Table 4). These EC50

values are intermediate to the range of acute val-

ues for saltwater animals.

Residues

Three insect species have been exposed to silver nitrate (Nehring, 1973)

and bioconcentration factors that range from 15 to 240 were calculated from

the data (Table 5). Bluegills were exposed during a 28—day test, and the

bioconcentration factor was less than one (U.S. EPA, 1978).

No data are available concerning bioconcentration of silver by saltwater

species.

Miscellaneous

Barge, et al. (1978) examined the toxicity of 11 trace metals. Silver

was the most toxic to the embryos and larvae of both rainbow trout and

largemouth bass, with the trout being more sensitive than the bass. Renewal

exposure was maintained from fertilization through four days post—hatch.

The marbled salamander was less sensitive than either fish species.

B-11

---

Soyer (1963) reported reduced development in sea urchin embryos at 0.5

ug/1 after a 52-hours exposure (Table 6) and Calabrese, et al. (1973) found

100 percent mortality among American oyster larvae after a 2-day exposure to

10 ug/l. The lower concentration is much lower than the chronic value for

the mysid shrimp. Also, summer glounder larvae are apparently more sen-

sitive than embryos, but the reverse may be true for winter flounder (Tables

1 and 6).

Summary

Acute toxicity data for silver are available for 10 species of fresh_

water animals from nine different taxonomic families that perform a wide

variety of community functions. The acute values range from 0.25 ug/1 for

Daphnia magna to 4,500 ug/1 for the scud, Gammarus pseudolimnaeus. Fish are

intermediate in sensitivity with acute values that range from 3.9 ug/1 for

the fathead minnow in soft water to 280 ug/1 for rainbow trout in hard water.

The data base indicates that acute toxicity of silver apparently de-

creases as hardness increases. Silver chloride seems to be much less toxic

than the very toxic silver nitrate. The relatively insoluble salts, silver

thiosulfate and silver sulfide, were the least toxic. On the other hand

silver iodide, when tested chronically at concentrations below its solubili-

ty limit, was as toxic as silver nitrate. Organic materials may also affect

the toxicity of silver because the acute toxicity of silver nitrate to Daph-

nia magna when food was added to the water was much less than when food was

not added to the water.

Four early life stage studies with the rainbow trout indicate that

chronic toxicity may be influenced by the age of embryos with which the test

was started and perhaps by the genetic variety of the rainbow trout.

8-12

---

Plants appear to be more resistant to silver than some animals, and thus

their well—being is assured if the more sensitive animals are protected.

The bioconcentration factors for silver range from less than one for blue

gill to 240 for insect larvae.

Acute values for saltwater organisms ranged from 4.7 ug/l for the summer

flounder to 1,400 ug/1 for the sheepshead minnow. A life—cycle toxicity

test conducted with the mysid shrimp showed that brood size was smaller at

33 ug/1 as compared to controls. The highest concentration tested which had

no statistically significant effect on reproduction and survival was 10

4/1. One saltwater alga has been tested, and reduced cell numbers were

recorded at 130 ug/l. No information is available showing the influence-of

environmental factors such as salinity, on toxicity of silver to saltwater

organisms.

CRITERIA

For freshwater aauatic life the concentration (in 4/1) of total recov-

erable?

silver?

should?

not?

exceed?

the?

numerical?

value given by

e

(1.72 Cln(hardness)]-6.52) at any time.

?

For example, at hardnesses of

50, 100, and 200 mg/1 as CaCO3

, the concentration of total recoverable

silver should not exceed 1.2, 4.1, and 13 ug/l, respectively, at any time.

The available data indicate that chronic toxicity to freshwater aauatic life

may occur at concentrations as low as 0.12 ug/1.

For saltwater aquatic life the concentration of total recoverable silver

should not exceed 2.3 ug/1 at any time. No data are available concerning

the chronic toxicity of silver to sensitive saltwater aauatic life.

B-13

---

Table 1.?

Acute values for silver

Hardness

Species Mean

feg/1 as

LCSO/EC50.1

Acute Value

Species

Method'

CaCO3)

(MG/1)

(Re/l)

Reference

FRESHWATER SPECIES

Rotifer,

Phi lodina acuticornis

S, U

25

1,400

-

Buikema, at al. 1974

Cladoceran,

Daphnia magna

S, U

40

1.5

-

U.S. EPA, 1978

Cladoceran,

Daphnia magna

S, U

48

0.66

-

Lemke, Manuscript

Cladoceran,

Daphnia magna

S, M

48

0.39

-

Lemke, Manuscript

Ciadoceran,

Daphnia

magnat

S, M

255

45

-

Lemke, Manuscript

Ciadoceran,

Daphnia magnat

5, N

255

49

-

Lemke, Manuscript

ra

I

a

Cladoceran,

Daphnia

ms

5, M

54

2.2

-

Lemke, Manuscript

Cladoceran,

Daphnia magna

S, M

54

2.9

-

Lemke, Manuscript

Cladoceran,

Daphnianum

S, M

46

0.90

-

Lemke, Manuscript

Ciadoceran,

Daphnia magna

S, M

46

1.0

-

Lemke, Manuscript

Cladoceran,

Daphnia magna

S, M

38

1.1

-

Lemke, Manuscript

Cladoceran,

Daphnia magna

S, M

40

0.64

-

Lemke, Manuscript

Cladoceran,

Daphnia magna

S, M

47

0.25

-

Chapman, et al.

Manuscript

Cladoceran,

Daphnia magna

S, M

._

t

?

75

15

-

Lemke, Manuscript

---

Table 1.?

(Continued)

Hardness

Species Mean

Species

Method*

(mg/I as

_CaCOA)

1:50/EC50"

(pal)

Acute Value

(pull)

Referenc

Ciadoceran,

Daphnia magna

S, M

Fr, 14

75

48

8.4

4,500

-

Lemke, Manuscript

Scud,

U.S. EPA, 1980a

Gammarus pseudollmnaeus

Midge,

Fr, M

4

3,200

-

U.S. EPA, 1980a

Tanytarsus dissimilis

Rainbow trout,

Salmocairdnerl

FT, M

31

5.3

-

Davies, et al. 1978

Rainbow trout,

Salmoualrdneri

Fr, M

20

6.2

-

Davies, et al. 1978

Rainbow trout,

Salmociairdneri_

FT, 1.1

26

8.1

-

Davies, et al. 1978

MI1

h

a

Rainbow trout,

Salmo gairdneri

FT, M

350

13

-

Davies, et al. 1978

In

Rainbow trout,

Salmociairdneri

FT, M

-

29

-

Hale,

?

1977

Rainbow trout,

Salmo gairdneri

Fr, M

48

18

-

Lemke, Manuscript

Rainbow trout,

Salmo gairdneri

Fr, M

48

16

-

Lemke, Manuscript

Rainbow trout,

5, M

48

20

-

Lemke, Manuscript

SalmogaIrdneri

Rainbow trout,

Salop

gairdneri

5, M

48

32

-

Lemke, Manuscript

Rainbow trout,

Salmo gairdneri

Fr, M

255

240

-

Lemke, Manuscript

Rainbow trout,

Salmo gairdneri

FT, M

255

170

Lemke, Manuscript

---

m

Table 1.?

(Continued)

Hardness

Species Mean

(mg/I as

LC50/EC50"

Acute Value

Species

Method+

_CaC071)

(1n1/1)

(ng/1)

Reference

Rainbow trout,

S, M

255

240

—

Lemke, Manuscript

Saimo qairdneri

Rainbow trout,

5, M

255

280

Lemke, Manuscript

Salmo clairdneri

Rainbow trout,

FT,

?

ta1

54

14

Lemke, Manuscript

Saimo qairdneri

Rainbow trout,

FT, M

54

12

Lemke, Manuscript

Salmocialrdneri

Rainbow trout,

5, 14

54

48

Lemke, Manuscript

Saint qairdneri

Rainbow trout,

5, 14

54

54

Lemke, Manuscript

Salmocialrdneri

Rainbow trout,

FT, 14

46

6.9

Lemke, Manuscript

Salmo qairdneri

Rainbow trout,

FT, M

46

8.4

Lemke, Manuscript

Salmocialrdneri

Rainbow trout,

S, M

46

12

Lemke, Manuscript

Saimpqairdneri

Rainbow trout,

5, M

46

110

Lemke, Manuscript

Salmo qairdneri

Rainbow trout,

Salmo clairdneri

Fr, M

29

7.6

Nebeker, et al.

Manuscript b

Rainbow trout,

FT, M

35

8.5

Leeks, Manuscript

Saimpqairdneri

Rainbow trout,

FT, M

42

9.7

Lemke, Manuscript

Salmo qairdneri

Rainbow trout,

S, 14

40

73

Lemke, Manuscript

Salmoclairdneri

---

Table 1.?

(Continued)

Hardness

Species Mean

fag/1 as

LC50/EC50.11

Acute Value

Species

Method*

CaCO3)

(Mail)

(Pal)

Reference

Rainbow trout,

Salvo clairdneri

S, M

37

84

-

Lemke, Manuscript

Rainbow trout,

Salnociairdneri

S, M

26

11

-

Nebeker, et al.

Manuscript b

Rainbow trout,

Salmo gairdneri

FT, M

75

11.5

-

Lemke, Manuscript

Rainbow trout,

Salvo gairdneri

Fr, M

75

10

-

Lemke, Manuscript

Rainbow trout,

Salvo gairdneri

S, M

75

25

-

Lemke, Manuscript

Rainbow trout,

Salm° clairdneri

5, M

75

22.5

Lemke, Manuscript

CCI

Fathead minnow,

Phosphates promotes

FT, M

48

11

-

U.S. EPA, 1980a

1-2

-4

Fathead minnow,

Pimephales promelas

FT, M

33

3.9

-

Goettl & Davies, 1978

Fathead minnow,

Pimephales promelas

FT, M

274

4.8

Goettl

41

Davies, 1978

Fathead minnow,

Pimephales promelas

FT, M

48

11

-

Lemke, Manuscript

Fathead minnow,

Pimephales promotes

FT, M

48

12

-

'

?

Lemke, Manuscript

Fathead minnow,

Pimephales promotes

S, M

48

30

Lemke, Manuscript

Fathead minnow,

Pimephales promelas

Sy M

48

23

-

Lemke, Manuscript

Fathead minnow,

Pimephales a

FT, M

255

150

Lemke, Manuscript

---

Table I.?

(Continued)

Hardness

Species Mean

(m9/1 as

LC5O/EC50"

Acute Value

Species

Method'

CeCO)—

(pq/l)

(P(/i)

Reference

Fathead minnow,

Pimephales promotes

FT, M

255

110

-

Lemke, Manuscript

Fathead minnow,

Pimephales promotes

5, M

255

230

-

Lemke, Manuscript

Fathead minnow,

Pimephales promelas

S, M

255

270

-

Lemke, Manuscript

Fathead minnow,

Pimephales promelas

FT, M

54

11

-

Lemke, Manuscript

Fathead minnow,

Pimephales promelas

S, M

54

14

-

Lemke, Manuscript

Fathead minnow,

Pimephales promelas

S, M

54

20

-

Lemke, Manuscript

0:1

Fathead minnow,

Pimephales prattles

FT, M

46

5.3

-

Lemke, Manuscript

I

i-,

co

Fathead minnow,

FT,

M

46

3.9

-

Leuke, Manuscript

Pimephales promelas

Fathead minnow,

Pimephalesprcasias

5, M

46

6.7

-

Lemke, Manuscript

Fathead minnow,

Pimephales promotes

S, M

46

12

-

Lemke, Manuscript

Fathead minnow,

Pimephales promotes

FT,

M

38

5.8

Lemke, Manuscript

Fathead minnow,

Pimephales promelas

FT,

M

40

5.6

-

Lemke, Manuscript

Fathead minnow,

Pimephales promelas

FT,

M

36

7.4

-

Nebeker, et al.

Manuscript b

Fathead minnow,

Pimephales promelas

5, M

25

12

-

Lemke, Manuscript

---

Table 1.

?

(Continued)

Hardness

Species Mean

(eg/1 as

LC50/EC50**

Acute Value

Species

Method'

CaCO3)

(4(1/1)

(p01)

Reference

Fathead minnow,

Pimephales promelas

S, M

39

9.7

-

Lemke, Manuscript

Fathead minnow,

Pimephales promelas

FT, M

75

6.3

-

Lemke, Manuscript

Fathead minnow,

Pimephales promelas

FT, M

75

5.0

Lemke, Manuscript

Fathead minnow,

Pimephales promelas

S, M

75

10

Lemke, Manuscript

Fathead minnow,

Pimephales promelas

S, H

75

8.7

Lemke, Manuscript

Fathead minnow,

Pimephales promelas

FT, M

38

16

EG&G Bionomics, 1979

C

I

Speckled dace,

Rhinichthys osculus

FT, M

30

4.9

-

Goettl & Davies, 1978

1.--•

1/4c)

Speckled dace,

Rhinichthys osculus

FT, M

250

14

-

Goetti & Davies, 1978

Flagfish,

Jordanella fioridae

FT, M

48

9.6

-

U.S. EPA, 1980a

Blueglil,

Lepomis macrochi rus

S, U

40

64

U.S. EPA, 1980a

Mottled sculpin,

Cottus bairdi

FT, M

30

5.3

Goettl & Davies, 1978

Mottled sculpin,

Cottus bairdi

FT, M

250

14

Goettl & Davies, 1978

---

Table I.?

(Continued)

Hardness

Species Mean

(mg/1 as

LC50/EC50"

Acute

Value

Species

Method*

?

CeCO3)

(pg/1)

(1101)

Reference

SALTWATER SPECIES

Bay scallop

?

(juvenile),

Argopecten irradians

S, U

33

33

Nelson, et al.

?1976

American oyster,

Crassostrea virginica

5, U

5.8

Calabrese, et al. 1973

American oyster,

Crassostrea virginica

S, U

24

-

MacInnes 41 Calabrese,

1978

American oyster,

Crassostrea virginica

S, U

35

-

MacInnes & Calabrese,

1978

American oyster,

Crassostrea virginica

5, U

32

20

Maclnnes 8 Calabrese,

1978

Nardshell clam,

Mercenaria mercenaria

S, U

21

21

Calabrese & Nelson,

1974

CO

0

ha

Copepod (adult),

S,

36

36

U.S. EPA, 1980b

Acartla tonsa

Mysid shrimp

?

(juvenile),

Mysidopsis bahla

FT, M

250

250

Lussler & Gentile,

1980

Atlantic sllversides

5, U

400

U.S. EPA, 1980b

(juvenile),

Menidia menidia

Atlantic sliversides

S, U

110

210

U.S. EPA, 1980b

(larval,

Menldia menidia

Summer flounder (larva),

Paralichthys dentatus

S, U

4.7

4.7

U.S. EPA, 1980b

Sheepshead minnow

?

4,

(juvenile),

Cyprinodon varlegatus

S, M

1,400

1,400

U.S. EPA,

?1980b

---

Table 1.

?

(Continued)

Hardness

Species Mean

(mg/I as

LC50/EC50"

Acute Value

Species

Method'

CaCO3)

(WW1)

(11(0)

Reference

Fourspine stickleback

(adult),

S, U

-

550

550

U.S. EPA, 1980b

Apeltes quadracus

Winter flounder (larva),

S, U

-

500

500

U.S.?EPA,?

19831)

Pseudopleuronectes

amer icanus

* $ = static, FT = flow-through, U = unmeasured, M = measured

**All freshwater and saltwater acute toxicity data were derived with silver nitrate and all

results are expressed as silver, not as the compound.

Freshwater:

Acute toxicity vs. hardness (see text)

Daphnia?

pats:

slope = 2.35, Intercept = -8.85,

r = 0.89, P = 0.01, N = 14

Rainbow trout: slope = 1.30, Intercept = -2.08, r = 0.75, P = 0.01, N = 30

Fathead minnow: slope = 1.50, Intercept = -3.52, r = 0.83, P = 0.01, N = 28

Arithmetic mean ?cute slope = 1.72

---

Table 2.?

Chronic values tor sliver

Hardness

Vag/1 as

Limits

Chronic

Value

Species

Test'

Chemical

CaCON)

(Pail).*

(PO/1).4

Reference

FRESHWATER SPECIES

Cladoceran,

Daphnia magna

LC

Silver nitrate

60

1.6-4.1

2.6

Nebeker, et al.

Manuscript b

Cladoceran,

Daphnia magna

LC

Silver nitrate

75

8.8-19.4

13

Nebeker, et al.

Manuscript b

Cladoceran,

Daphnia magna

LC

Silver nitrate

180

3.4-8.0

5.2

Nebeker, et al.

Manuscript b

Cladoceran,

Daphnia

LC

Silver nitrate

48

2.7-3.9

3.2

Nebeker, et al.

Manuscript a

Cladoceran,

Daphnia magna

LC

Silver nitrate

70

10.5-21.2

15

Nebeker, et al.

Manuscript a

tO

Cladoceran,

Daphnia

magna

LC

Silver nitrate

70

19.8-41.2

29

Nebeker, et al.

Manuscript a

Rainbow trout,

SalmoclaIrdnerl

to

to

ELS

Sliver nitrate

28

0.09-0.17

0.12

Davies, et al. 1978

Rainbow trout,

(steetheadl,

Salm gairdnerl

ELS

Silver nitrate

37

8.9-15.9

12

Nebeker, et al.

Manuscript c

SALTWATER SPECIES

Mysld shrimp,

MysIdopsis bahla

LC

Sliver nitrate

10-33

18

Lussler 8 Gentile,

1980

• LC = life cycle or partial life cycle; ELS = early life stage

**Results are expressed as silver, Not as the

compound

---

Table 2. (Continued)

Acute-Chronic Ratios

Acute Value

Chronic Value

Species

(w)/1)

tug/I)

Ratio

Silver Nitrate

Ciadoceran,

43*

22**

2.0

Daphnisimmit

Rainbow trout,

6.5***

0.12

54

Salmogairdneri

Mysid shrimp,

250

18

14

Mysidopsis bahia

*

Result of acute test with food added to test solutions (Table 6).

** Arithmetic mean of 15 and 29 pg/1 (Table 2).

***Arithmetic mean of 5.3, 6.2 and 8.1 pg/I (Table 1)

---

Table 3. Species mean acute Intercepts, values, and acute-chronic

ratios for sliver

Rank*

Species Moen

Acute Intercept

Species?

(p1/1)

Species Mean

Acute-Chronic

Ratio

FRESHWATER SPECIES

10

Scud,

Gaaaarus pseudo I imnaeus

5.77

9

Rotifer,

Phi lodina acuticornls

5.52

8

Midge,

Tanytarsus dIssimIlls

4.11

7

Bluegill,

Lepomls macrochirus

0.112

6

Rainbow trout,

Salmo oairdneri

0.0230

54

5

Mottled sculpin,

0.015

CO

Cottus bairdl

43.

4

Speckled dace,

Rhinichthysosculus

0.014

3

Flagfisn,

Jordanella florida

0.0123

2

Fathead minnow,

Pimephales promelas

0.0121

I

Cladoceran,

Daphnia magna

0.00152

2.0

Species Mean?

Species Mean

Acute Value

?

Acute-Chronlc

Ranh'

?

it

Species

?

(pq/l)

? Ratio

SALTWATER SPECIES

10?

Sheepshead minnow,

?

1,400

Cyprinodon varieciatus

---

Table 3. (Continued)

Species Mean?

Species Mean

Acute Value?

Acute-Chronic

Rank*

?

Species

?

(tIg/i)

?

Ratio

9?

Fourspine stickleback,

?

550

?

-

Apeltes quadracus

=

8?

Winter flounder,

? 500

Pseudop ieuronectes americanus

7?

Mysld shrimp,

?

250?

14

Mysldopsis bahia

6?

Atlantic sllversides,?

210?

-

Menidia menidla

5?

Copepod,

?

36

?

-

Acartla tonsa

4?

Bay scallop,?

33?

-

Arqopecten irradlans

3?

Mercenarla

Hard shell

mercenarla

clam,?

21 -

2

?

American oyster,?

20?

-

Crassostrea vlrginlca

1?

Summer flounder,?

4.7

?

-

Parallchthys dentatus

* Ranked from least sensitive to most sensitive

based

on species mean

acute Intercept or species mean acute value.

Freshwater:

Final Acute Intercept = 0.00147 pg/I

Natural logarithm of 0.00147 = -6.52

Acute slope = 1.72 (see Table 1)

Final Acute Equation

= e(1.7211n(hardness)I-6.52)

Saltwater Final Acute Value = 2.28 pg/I

---

Table 4.

?

Plant values for silver

Result'

Species

Effect

(moil)

Reference

FRESHWATER SPECIES

Alga (green),

Chlorella fusca

Complete inhibition

of growth

100**

Stokes, et al. 1973

Alga (green),

Chlorella fusca

Inhibition of

growth

50**

Stokes, et al. 1973

Alga (green),

Chlorella pyrenoidosa

Inhibition of

growth

100

Fitzgerald, 1967

Alga (green),

Chlorella pyrenoidosa

Lethal

1,000

Fitzgerald,?1967

Alga (green),

Chlorella variegate

Toxic

420

Palmer & Maloney,

I955

0:1

Alga (green),

Chlorella vulgaris

Inhibition of

growth

50**

Hutchinson &

Stokes, 1975

I

mct

Alga (green),

Chlorella vulgaris

,

Inhibiton of

growth

Complete Inhibition

of growth

30**

100**

Stokes, et al. 1973

Alga (green),

Stokes, et al.

1973

Scenedesmus acuminatus

Alge (green),

Scenedesmus acutiformis

Complete Inhibition

of growth

200**

Stokes, et al.?1973.

Alga (green),

Scenedesmus obliquus

Toxic

420

Palmer I. Maloney,

1955

Alga (green),

Scenedesmus obliquus

Threshold toxicity

50

BrIngman t. Kuhn,

1959

Alga (diatom).

Gomphonema parvulum

Toxic

420

Palmer I. Maloney,

1955

Alga (diatom),

Nitzschla palea

Toxic

420

Palmer & Maloney,

1955

---

Table 4. (Continued)

Result*

Species

?

Effect?

(110/1)

?

Reference

Alga (blue-green),?

Toxic?

420

?

Palmer & Maloney,

Cylindrospermum

?

1955

lichenlforme

Alga (blue-green),

?

Toxic?

420?Palmer & Maloney,

Mlcrocystis aeruginosa?

1955

Waterweed,

?

Inhibition of?

100

?Brown & Rattigan,

Elodea canadensis

?

oxygen evolution?

1979

Waterweed,

?

Phytotoxlcity

? 7,500

?

Brown & Rattigan,

Elodea canadensis

?

1979

Duckweed,?

Phytotoxicity?

270?

Brown & Rattigan,

Lorna minor?

1979

SALTWATER SPECIES

Alga,

?

96-hr EC50,

?

170?

U.S. EPA, 1978

NJ

?

Skeletonema costatum?

chlorophyll a

■J

Alga,?

96-it EC50,

?

130?

U.S. EPA, 1978

Skeletonema costatum

?call numbers

• All freshwater and saltwater plant values were derived with silver nitrate

except where Indicated and all results are expressed as sliver, not as

the ccmpound.

"Authors did not specify sliver ccmpound.

---

Table 5.

?

Residues' for silver

Hardness

(ag/I as

?

Dioconcentration

Duration

(days)

Reference

Species

Tissue

CaCOtI

factor

FRESHWATER SPECIES

Mayfly,

Ephemerella orandis

Whole body

Whole body

62

65

35**

240**

7

10

Nehring, 1973

Nehring,

?

1973

Mayfly,

Ephemerella orandis

Whole body

34

15"

3

Nehring,

?

1973

Stonefly,

Claasenia sabulosa

Whole body

32

21**

6

Nehring, 1973

Stonefly,

Pteronarcys californica

Stonefly,

Whole body

31

17

0

*

*

7

Nehring, 1973

N.)

03

Pteronarcys canto/mica

30

79"

15

Nehring, 1973

Stonefly,

Pteronarcys californica

Bilieglli,

Whole body

Whole body

-

<1

28

U.S. EPA, 1978

Lepomis macrochi rus

' All results were derived with silver nitrate.

**81oconcentration factors have been converted from dry weight to wet weight.

---

Hardness

(m8/1 as

Table 6.?

Other data for silver

Result*

Species

CaCO3

)

Duration?

Effect

luralt

Reference

FRESHWATER SPECIES

Ciadoceran,

274

24

hrs

LC50

3.4

Bringmann & Kuhn,

1977

Daphnia

magna

Cladoceran,

Daphnia

magna

47

48

hrs

LC50**

9.5

Chapman, et al.

Manuscript

Ciadoceran,

70

48

hrs

LC50**

43

Lemke, Manuscript

Daphnia

magna

Mayfly,

31

7

days

LC50

<4

Nehring,

1973

Ephemereliagrandis

Mayfly,

30

15

days

LC50

8.8

Nehring,

1973

Sphemerella grandis

Stonefly,

65

10 days

LC50

<9

Nehring,

1973

Pteronarcys californica

Rainbow trout,

93-105

28

days

LC50

10

Blrge, et al.?

1978

Salm° !lairdneri

Rainbow trout

(eyed

embryos),

28

13

mos

Chronic

limits***

0.03-0.06

Davies & Goetti,

1978

Salmociairdneri

Rainbow trout

(green embryos),

29

10

mos

Chronic

limits***

0.18-0.40

Davies & Goettl,

1978

Salmo gairdneri

Fathead minnow,

Pimephales promelas

38

96

hrs

100% mortality

(silver thio-

sulfate)

280,000

EG8G Bionomics,

1979

Fathead minnow,

Pimephales promelas

38

96

hrs

N3 mortality

(silver sul-

fide gel)

240,000

EG&G Bionomics,

1979

Fathead minnow,

Pimephales promelas

38

96

hrs

No mortality

(silver sul-

fide)

13,000

EG&G Bionomics,

1979

---

06

to

0

Table 6. (Continued)

Species

Fathead minnow,

Pimephales promelas

Fathead minnow,

Pimephales promelas

Fathead minnow,

Pimephales promelas,

Fathead minnow,

Pimephales promelas

Bluegill,

Lepomis macrochirus

Largemouth bass,

Micropterus salmoldes

Largemouth bass,

Micropterus salmoldes

Marbled salamander,

Ambystana opacum

Red alga (snarling),

Plumarla elegans

Bay scallop (Juvenile).

Argopecten Irradians

American oyster (larva),

Crassostrea vIrdinIca

American oyster (larva),

Crassostrea vIrdinica

American oyster,

Crassostrea yirginica

Hardness

(wg/1 as

?

Result*

CaCO5) _?

Duration?

Effect

?

(ual)?

Reference

96 hrs?

LC50 (2,000 mg

?

5,600?

EG&G

Blonomics, 1979

C1-/I)

96 hrs?

LC50 (1,000 mg?

510?

EG&G Bionomics, 1979

C1-/I)

96 hrs

?

LC50 (500 mg?

2,100?

EG&G Bloncmics, 1979

CI-in

96 hrs

?

LC50 (silver

?

>250,000?

Terhaar, et al. 1972

thiosulfate)

6 mos?

Tolerated

8 days?

LC50

24 hrs?

Lethal

8 days?

LC50

SALTWATER SPECIES

18 hrs?

98% mortality

?

1,000

?

Boney, et al. 1959

4 days?

15% Increased?

22

?

Nelson, et al. 1976

02 uptake

2 days?

100% mortality?

10?

Calabrese, et al. 1973

12 days?

50% mortality

?

25?

Calabrese, et al. 1977

4 days?

Significant?

100?

Thurberg, et al. 1974

Increase In

oxygen consumption

38

38

38

131

180

93-105

180

93-105

?

70.?

Coleman & Cearley, 1974

?

'11D?

Birge, et al. 1978

?

70?

Coleman & Cearley, 1974

?

240?

Blrge, et al. 1978

---

0.1

Table 6.?

(Continued)

Hardness

(mg/1 as

Result*

Species

CaCO3)

Duration

Effect

Wan

Reference

Hard-shell clam,

Mercenaria mercenaria

2 days

100% mortalit

45

Calabrese & Nelson,

1974

Hard-shell clam,

Mercenaria mercenaria

4 days

Significant

Increase?

In

oxygen consumption

100

Thurberg, et al. 1974

Hard-shell clam (larva),

10 days

LC50

32

Calabrese, et al. 1977

Mercenaria mercenaria

Soft-shell?clam,

Mya arenaria

4 days

Significant

increase In

oxygen consumption

100 Thurberg, et al.

?1974

Blue mussel,

Mytilus edulls

4 days

Significant

increase In

oxygen consumption

100

Thurberg, et al. 1974

Mud snail,

Nassar lus obsoletus

3 days

Depression of

oxygen consumption

500

Macinnes & Thurberg,

1973

Mud snail,

Nassarius obsoletus

3 days

Distressed beha-

vior, snail unable

to move

250

Macinnes & Thurberg,

1973

Surf clam (larva),

Splsula solidissIma

15 days

Significant

Increase

?

In

oxygen consumption

50

Thurberg, et al. 1975

Surf clam (Juvenile),

Splsula solidissima

4 days

Significant

increase in

oxygen consumption

10

Thurberg, et al. 1975

Surf clam (adult),

Splsula solidisslma

4 days

Significant

increase In

oxygen consumption

50

Thurberg, et al. 1975

Cannon barnacle (adult),

2 days

90% mortality

400

Clarke, 1947

Balanus balanoldes

Cannon

barnacle (adult),

5 days

90% mortality

200

Clarke, 1947

Balanus balanoides

---

Table 6. (Continued)

Species

Sea urchin,

Arbacia limmla

Mummichog (adult),

Fundulus heteroclitus

Mummichog (adult),

Fundulus heteroclitus

Cunner,

tautogolabrus adspersus

Cunner,

Tautogolabrus adspersus

Hardness

(mg/1 as

CaCO3)

Duration

52 hrs

4 days

2 days

4 days

4 days

Effect

Reduced embryo

development

significantly

in vivo Inhibl-

ITora

enzymes

3 liver

Degeneration of

lateral line and

olfactory sensory

structure

Significant

depression of

oxygen consumption

Decreased oxygen

consumption

depressed activity

of a liver enzyme

7::;1:: Reference

0.5?

Sayer, 1963

30

?

Jackim, et al. 1970

500?

Gardner, 1975

120

?

Thurberg & Collier,

1977

500?

Gould & Macinnes, 1977

Summer flounder (embryo),

Parallchthys dentatus

Summer

flounder (embryo),

Parallchthys dentatus

Summer flounder (embryo),

Parallchthys dentatus

Summer flounder (embryo),

Parallchthys dentatus

Winter flounder (embryo),

Pseudop leuronectes

americanus

96 hrs

?

LC50

?

140

?

U.S. EPA, 1960b

96 hrs

?

LC50?

8.0?

U.S. EPA, 1980b

96 hrs

?

LC50

?

16?

U.S. EPA, 1980b

96 hrs

?

LC50

?

48

?

U.S. EPA, 1960b

96 hrs?

LC50

?

450

?

U.S. EPA, 1980b

---

Table 6. (Continued)

Hardness

(mg/1

as?

Result*

Species?

CaC0i)?

Duration? Effect

?

(nal)

?

Reference

Winter flounder (embryo),

?

-

?

96 hrs?

LC50

? 300?

U.S.'EPA, 1980b

Pseudop leuronectes

amerlcanus

Winter flounder (embryo),?

-

? 96 hrs?

LC50?

270?

U.S. EPA, 1980b

Pseudop leuronectes

amerlcanus

Winter flounder (embryo),

? 96 hrs

?

LC50? 200?

U.S. EPA, 1980b

Pseudop I euronectes

amer I can us

* All freshwater and saltwater data were derived with sliver nitrate except where indicated and all results

are expressed as sliver, not as the compound.

** Animals were fed during test.

***Tests on silver Iodide.

---

REFERENCES

Birge, W.J., et al. 1978. Embryo—larval Bioassays on Inorganic Coal Ele-

ments and in situ Biomonitoring of Coal—waste Effluents. In: D.E. Samuel,

et al. (eds.), Surface Mining and Fish/Wildlife Needs in the Eastern United

States. U.S. Dept. Int. Fish Wildl. Serv., FWS/OBS-78/81, Dec. 1978. p. 97.

Boney, A.D., et al. 1959. The effects of various poisons on the growth and

viability of sporelings of the red alga Plumaria elegans (Bonnem.) Schm.

Biochem. Pharmacol. 2: 37.

Bringmann, G. and R. Kuhn. 1959. Comparative water—toxicology investiga-

tions on bacteria, algae, and daphnids. Ges. Ind. 80: 115.

Bringmann, V.G. and R. Kuhn. 1977. Report on the damaging action of water

pollutants on Daphnia magna. Wass. Abwass—Forsch. 10. 5: 161.

Brown, B.T. and B.M. Rattigan. 1979. Toxicity of soluble copper and other

metal ions to Elodea canadensis. Environ. Pollut. 20: 303.

Buikema, A.L., Jr., et al. ?

1974.?

Evaluation of Philodina acuticornis

(Rotifera) as a bioassay organism for heavy metals. ?

Water Res. Bull.

10: 648.

B-34

---

Calabrese, A. and D.A. Nelson.

1974.

Inhibition of embryonic development

of the hard clam Mercenaria mercenaria by heavy metals.

Bull.

Environ. Con

tam. Toxicol. 11:

92.

Calabrese, A., et al.

1973.

The toxicity of heavy metals to the embryos of

the American oyster (Crassostrea virginica). Mar.

Biol. 18: 162.

Calabrese, A., et al.

?

1977.?

Effects of cadmium, mercury and silver on

marine animals. Mar. Fish. Rev. 39: 5.

Chambers, C.W. and C.M. Proctor. 1960.

The bacteriological and chemical

behavior of silver in low concentrations. U.S. Dept. Health, Edu. and Wel-

fare. PHS Tech. Rep.

W60-4. p. 1.

Chapman, G.A., et al. Effects of water hardness on the toxicity of metals

to Daphnia magna. Status Report. U.S. Environ. Prot. Agency, Corvallis,

Oregon. (Manuscript)

Clarke, G.L. 1947.

Poisoning and recovery in barnacles and mussels.

Biol.

Bull. 92: 73.

Coleman, R.L. and J. Cearley.

1974.

Silver toxicity and accumulation in

largemouth bass and bluegill.

Bull.

Environ. Contam. Toxicol. 12: 53.

B-35

---

Davies, P.H. and J.P. Goettl, Jr.

?

1978. Evaluation of the Potential Im-

pacts of Silver and/or Silver Iodide on Rainbow Trout in Laboratory and High

Mountain Lake Environments. In: D.A. Klein (ed.), Environmental Impacts of

Artificial Ice Nucleating Agents.?

Dowden, Hutchinson and Ross, Inc.,

Stroudsburg, Pennsylvania. p. 149.

Davies, P.H., et al.?

1978.?

Toxicity of silver to rainbow trout (Salmo

gairdneri). Water Res. 12: 113.

Dyck, W. 1968. Adsorption and coprecipitation of silver on hydrous ferric

oxides. Can. Jour. Chem. 46: 1441.

EG&G Bionomics. 1979. The acute toxicity of various silver compounds to

the fathead minnow (Pimephales promelas). Natl. Assoc. Photo. Manu., Inc.,

Harrison, New York. p. 1, Tables 1-30, Appendix I—IV.

Fitzgerald, G.P. 1967. The algistatic properties of silver. Water Sew.

Works. 114: 185.

Gardner, G.R. 1975. Chemically Induced Lesions in Estuarine or Marine Tel-

eosts.

?

In: W.E. Ribeline and G. Migaki (eds.), The Pathology of Fishes.

Univ. Wisconsin Press, Madison, Wisconsin. p. 657.

Goettl, J.P., Jr. and P.H. Davies. 1978. Water pollution studies. Job 6.

Study of the effects of metallic ions on fish and aquatic organisms. Job

Progress Rep. Fed. Aid Proj. F-33—R-13. Colorado Div. Wildl. p. 6.

8-36

---

Gould, E. and J.R. Maclnnes. 1977. Short—term effects of two silver salts

on tissue respiration and enzyme activity in the cunner (Tautogalabrus ad—

l

anai).

Bull. Environ. Contam. Toxicol. 18: 401.

Hale, J.G. 1977. Toxicity of metal mining wastes. Bull. Environ. Contam.

Toxicol. 17: 66.

Hem, J.D. 1970. Study and interpretation of the chemical characteristics

of natural waters. U.S. Geol. Surv. Water—Supply Pap. 1473. Washington,

D.C. p. 202.

Hutchinson, T.C. and P.M. Stokes. 1975. Heavy metal toxicity and algal bi-

oassays. Water Quality Parameters. ASTM SPT 573: 320.

Jackim, E., et al. 1970. Effects of metal poisoning on five liver enzymes

in the killifish (Fundulus heteroclitus). ?

Jour. Fish. Res. Board Can.

27: 383.

Kharkar, D.P., et al. 1968. Stream supply of dissolved silver, molybdenum,

antimony, selenium, chromium, cobalt, rubidium, and cesium to the oceans.

Geochim. Cosmochim. Acta. 32: 285.

Lemke, A.E.

?

Comprehensive report — Interlaboratory comparison:

?

acute

testing set. (Manuscript).

R-37

---

Lussier, S.L. and J.H. Gentile. Chronic toxicity of copper and silver to

the mysid shrimp Mysidopsis bahia.

?

U.S. Environ. Prot Agency,?

Environ.

Res. Lab., Narragansett, Rhode Island. (Manuscript)

Maclnnes, J.R. and A. Calabrese. 1978. Responses of Embryos of the Ameri-

can Oyster Crassostrea virginica to Heavy Metals at Different Temperatures.

In: D.S. Mclusky and A.J. Berry (eds.), Physiology and Behavior of Marine

Organisms. Proc. 12th European Symp. on Marine Biol. p. 195.

Maclnnes, J.R. and F.P. Thurberg. 1973. Effects of metals on the behavior

and oxygen consumption of the mud snail. Mar. Pollut. Bull. 4: 185.

Nebeker, A.V., et al. Toxicity of silver and endosulfan to rainbow trout,

fathead minnow, and Daphnia magna. (Manuscript a)

Nebeker, A.V.,?

et al.?

Daphnia macla static renewal life cycle tests.

Final report of round—robin testing. U.S. Environ. Prot. Agency.

?

(Manu-

script b)

I

s

?

Nebeker, A.V., et al. Sensitivity of steelhead early life stages (embryo

larval) to silver nitrate. (Manuscript c)

Nehring, R.B.?

1973. Heavy metal toxicity in two species of aquatic in-

sects. Masters Thesis. Colorado State Univ., Fort Collins, Colorado.

Nehring, R.B. 1976. Aquatic insects as biological monitors of heavy metal

pollution. Bull. Environ. Contam. Toxicol. 15: 147.

B-38

---

Nelson, D.A., et al. 1976. Biological effects of heavy metals on juvenile

bay scallops, Argopecten irradians, in short—term exposures. Bull. Environ.

Contam. Toxicol. 16: 275.

Palmer, C.M. and T.E. Maloney. 1955. Preliminary screening for potential

algicides. Ohio Jour. Sci. 55: 1.

Soyer, J. 1963. Contribution a l'etude des effects biologiques du mercure

et de l'argent dans l'eau de mer. Vie et Milieu. 14: 1.

Stokes, P.M., et al. 1973. Heavy metal tolerance in algae isolated from

polluted lakes near the Sudbury, Ontario smelters. Water Pollut. Res. Can.

8: 178.

Terhaar, G.J., et al. 1972. Toxicity of photographic processing chemicals

to fish. Photographic Sci. Engr. 16: 370.

Thurberg, F.P. and R.S. Collier. 1977. Respiratory response of cunners to

silver. Mar. Pollut. Bull. 8: 40.

Thurberg, F.P., et al. 1974. Effects of Silver on Oxygen Consumption of

Bivalves at Various Salinities. In: F.J. Vernberg and W.B. Vernberg (eds.),

Pollution and Physiology of Marine Organisms. Academic Press, New York.

p. 67.

8-39

---

Thurberg, F.P., et al. 1975. Respiratory Response of Larval, Juvenile, and

Adult Surf Clams, Spisula solidissima, to Silver.

?

In: J.J. Cech, Jr., et

al. (eds.), Respiration of Marine Organisms. Trigom. Pub., South Portland,

Maine. p. 41.

U.S. EPA. 1978. In—depth studies on health and environmental impacts of

selected water pollutants.?

EPA Contract No. 68-01-4646.

?

U.S. Environ.

Prot. Agency, Washington, D.C.

U.S. EPA. 1980a. Unpublished laboratory data. Environ. Res. Lab., Duluth,

Minnesota.

U.S. EPA. 1980b. Unpublished laboratory data. Environ. Res. Lab., Nar-

ragansett, Rhode Island.

B-40

---

Mammalian Toxicology and Human Health Effects

EXPOSURE

Silver is a frequent contaminant of normal human tissues, gen-

erally

at

c

t 1 mg/kg in the ash (Tipton and Cook, 1963). For an

extensive tabulation of silver concentrations in the tissues of

normal individuals, disease victims, and people with argyria, see

Smith and Carson •(1977). Anspaugh, et al. (1971) of Lawrence

Livermore Laboratory have also compiled data from the published

literature on the silver content of human tissues. Most reported

values have been based on ash weight or dry weight and are rather

difficult to compare since analytical procedures at such low con-

centrations vary in their accuracies. Data in Table 1, adapted

from Hamilton, et al. (1972/1973), however, seems to be in agree-

ment with most reports.

Silver concentrations in human tissues apparently increase

with age. It has been detected, however, in human placentae (Mis-

chel, 1956) and fetal livers (Robkin, et al. 1973). Absorption

upon exposure or the extent of exposure, itself, may vary consider-

ably among normals as reflected in tissue levels. For example, the

silver content of the hair of school children from 21 school dis-

tricts in Silesia, Poland, ranged from 0.23 to 1.96 mg/kg (average

0.69 mg/kg; analysis by neutron activation) (Dutkiewicz, et al.

1978).

Ingestion from Water

Natural fresh waters contain an average of 0.2 pg/1 silver,

and seawater contains 0.24 pg/1 (Boyle, 1968). Water-analysis data

from many literature sources have been combined in Table 2.

C-

1

---

TABLE 1

Silver Content in Healthy Human Tissues in the United Kingdom*

No.

Ag, ug/g Wet Wt.

Blood?

(U.K. Master Mix)

0.01?

+ 0.005

Blood?

(U.K.)

93

0.008 + 0.0008

Whole brain

10

0.004 + 0.002

Frontal lobe

2

0.003 + 0.001

Basal ganglia

2

0.004 + 0.002

Whole kidney

8

0.002 + 0.0002

Cortex

8

0.001 + 0.0002

Medulla

8

0.002 + 0.0002

Liver

11

0.006 + 0.002

Lung

11

0.002 + 0.0001

Lymph nodes

6

0.001 + 0.0002

Muscle

6

0.002 + 0.0005

Testis

5

0.002 + 0.0004

Ovary

6

0.002 + 0.0005

Bone (rib)

?

from patient who

lived in:

Hard water area

22

1.1 + 0.2?

(ash)

Soft water area

22

1.1 + 0.2

?

(ash)

*Source: Hamilton, et al. 1972/1973

C-2

---

0.002-0.216

St. Lads, Missouri

0

0

0.02

0.001-4.5

0.11 (0.13 neutron

activation anaL)

0.01-0.7

0.13

0.2

5.3-9.1

?

0

?

Up

to 43,000 in

?

Steamboat Springs,

siliceous

?

Nevada

36

504

100-300 in

water

up to 13,000,000

in residue

10

10

Niland, California

Near

Salton Sea,

California

Acid

Alkaline?

-

to neutral

0.1? California

207?

Comstock Lode,

Nevada

3.3? Comstock Lode,

Nevada

TABLE 2

Silver in Natural U.S. Waters

Detection

Type of Water

?

pH

?

Frequency

?

Ag Content (ppb)

?

Loc.ation

?

Remarks

?

Reference

kJ

Rainfall

Precipitation

Precipitation

(Agl seeded)

Snowfall

(Agl seeded)

Freshwater

Springs and surface

freshwaters

Hot springs

SO7

, NaC1,

l?

fate

HCDcarbonate3-'

borate,

Gul-

Steam yell: Neel,

CaC1 Eel

Spring and

well waters

Desert well brines

Oil well trines

Vadan wine

waters SiO2,

Mg, Fe, Al, Ca, Cu,

Mn, SO,

Deep mile

waters sul-

fate, carbonate

Typically 0.01-0.3

Fit Ag

Widely diffused,

marked

regional variations.

Surface waters

u‘nally

have

less Ag than springs

Geothermal brines have

higher calm of Ag and

other trace metals than

municipal cc industrial waste-

waters. Two of

these samples

had Ag content in excess of

chinking water standards.

Temperature,

116-170°F

Rattonetti, 1974

Cooper & Jolly, 1969

Warburton, 1969

Hawkes & Webb, 1962

Bowery

1966

Boyle, 1968

Boyle, 1968

Boyle, 1968

Bradford, 1971

Boyle, 1968

Boyle, 1968

Boyle, 1968

---

Lanford, 1969

Bowen, 1966

Boyle, 1968

Samples collected

from 170 High

Sierra Lakes.

Boyle, 1968

Boyle, 1968

Bradford, et aL 1968

Merritt, 1971

TABLE 2 (Continued)

Type of Water

Detection

PH

?

Frequency?

Ag Content (ppb)

?

Location

Remarks

?

Reference

Seawater

-

-

? 0.1.5-2.9 (0.291?

AIL

?

Run-off is of minor impor-

average tance. Like Ba,

trates

Ag

with

ooncerr-increasing

depth

and in areas of high organic

productivity. May be lees

ccocentrated near

shores.

0.3

0.16?

- Gulf of Mexico

0.145

? 40 miles west of

San Francisco

0.15-0.3

0.1-3.5?

-

Maine

86%-

0.1

6.0 (maximum)(average)?California

.

0.006-0.7? Near Chalk River

Nuclear Laboratory

100%

?

0.8 (1.0 maximum) Coachella Valley,

California

33 i

?

10

?

Near

Sudbury,

Ontario

10-200

?

U

.S.

(in residues)

Seawater

Seawater

Seawater

Seawater

Lakes

Lakes

Lake, ground,

and Ottawa

River water

Agrirotural

drainage

Lakes

Lakes, seams,

and rivers

Bradford, 1971

After 60 years of

?

Stokes, et aL 1973

copper smelting

Boyle, 1968

---

5.5%

TABLE 2 (Continued)

Detection

Type of Water

?

PH

Frequency?

A9 Content (ppb)

?

Location

?

Remarks

?

Reference

22.4 8

6.6 %

14.3%

29.6%

Detection limits fcc

Kopp 6 Kroner were ppb.

includes New Jersey

to

Groundwater

Ethology:

Slate

Shale

Granite

Shale and schist

Cretaceous

sand

Tertiary lime

Standard deviation =

49 based on samples

taken at 25 locations.

Surface waters

Stream water

Rivers

Large rivers

U.S. river basins

Northeast

River Basin

St-

Lawrence River

Hudson River

North Atlantic

River Basin

Delaware River

Delaware River

Susquehanna River

Susquehanna River

Southeast

River Basin

Apalachicrda River

Mobile River

Neuse River

Reuse River

Reuse River

Neuse River

Neese River

Neuse River

Neuse River

0.10-3.0

(0.3 average)

0.00006-0.0062

up to LO

0-0.94

2.6 (38 maximum)

1.9 (6.0 maximum)

2.6 (6.0 maximum)

0.13-0.59

0.9 (2.5 maximum)

LI (8.2 maximum)

3

0-0.29

039

0.4 (0.7 maximum)

0.058-0.11

0.085-0.28

0.52

0.56

0.25

0.86

0.30

0.37 (average)

St. Louis, Missouri

N. America 6 Norway

North America

U.S.

Northeastern U.S.

Mamma, New York

Green Island,

New York

U.S.

Trenton,

NJ

Calowingo, M D

U.S.

Near Blaustown,

Florida

Mt.

Vernal Landing,

Alabama

North Carolina

North Carolina

North Carolina

North Carolina

North Carolina

North Carolina

North Carolina

Klein, 1972

Boyle, 1968

Boyle, 1968

Kopp 6 Kroner, 1970

Page, 1974

Kopp 6 Kroner, 1970

Kopp 6 Kroner, 1970

Durum 6 !laity, 1961

Kopp 6 Kroner, 1970

Kopp 6 Kroner, 1970

Kopp &

Kroner, 1967

Durum &

Rarity, 1961

Andaman, 1973

Kopp 6 Kroner, 1970

Durum 6 Haffty, 1961

Andelman, 1973

Andelm an, 1973

Andelman, 1973

Andelman, 1973

Andelman, 1973

Andelman, 1973

Andelman, 1973

California

?

Myers, et aL 1958

---

Detection

Type a Water

PH

Frequency

?

Ag Content (ppb)

Location

Remarks

Reference

Pittsburgh,

Pennsylvania

Pittsburgh,

Pennsylvania

Pittsburgh,

Pennsylvania

Wiz-tie-1d Dam, West

Virginia

Tennessee and

adjacent areas

2.1 (8.2 maximum) U.S.

?

0.05-1.0?

West

Newton,

Pennsylvania

?

0.5-1.3

?

Apollo, Pennsylvania

2.0

2.0 (4.7 maximum)

4.0

1.2 (3.0 maximum)

0.6-1

5.3 (9.0 maximum) U.S.

ND?

Cleveland, Ohio

5.0%

8.3%

5.0%

12.9%

608

14 1

6.4%

0

0%

5.4

%

TABLE 2 (Continued)

Tennessee

River Basin

Ohio River Basin

Youghiogheny River

Kiskimintas River

Allegheny River

Monongahela River

Monongahela River

Kanawha River

Ohio River

Great Lakes

Lake Erie Basin

Cuyahoga River

Maumee River

Maumee River

Upper Mississippi.

River Basin

Western Great

Lakes Basin

Detroit River

Missouri River

Basin

3.4 (6.0 maximum)

1.4

1-0 (3.8 maximum)

1.2 (1.5 maximum)

U.S.

U.S.

Detroit, Michigan

U.S.

Kopp 6 Kroner, 1970

Kopp & Kroner, 1970

Kopp S Kramer, 1967

Kopp 6 Kroner, 1970

Kopp S Kroner, 1970

Kopp & Kroner, 1967

Kopp S Kroner, 1970

Kramer S Kopp, 1965

Kroner S Kopp, 1965

Kopp 6 Kroner, 1970

Kopp & Kroner, 1967

Kopp & Kramer, 1970

Kopp & Kroner, 1970

Kapp & Kroner, 1970

Kopp & Kroner, 1970

Kopp S Kroner, 1970

rn

These primary streams re-

ceive acid mine drainage,

but Ag was not detected

50

miles

downstream in

Toronto, Ohio

Receives effluents from

automotive, meat-pacicaghtg

and paper industries

Travels from Ft. Wayne,

Indiana through industrial

complexes and receives agri-

cultural, petrochemical and

metal waking wastes.

?

12.5%?

5.3 (9.0 maximum) Toledo, Ohio

?

12.5%

?

3.6 (6.0 maximum) Toledo, Ohio

---

NPABLE 2 (Continued)

Type of Water

Detection

PH

?

Frequency

Ag Content

Location

Remarks

Reference

Southwest-Lower

4.5%

4.3 (9.0 maximum)

U.S.

Kopp

&

Kroner, 1970

Mis:sisaippi Basin

Mississippi River

0.?

0.22

Baton Rouge,

Louisiana

Durum & Harty, 1961

Mien-WAR:4

River

0.26

Andelman, 1973

Misalssippi River

12

Kroner

& Kopp, 1965

Missouri River

57

0.2-20

Kroner

& Kopp, 1965

Atchafalaya River

ND-0.33

Knots Springs,

Louisiana

Durum & Haffty, 1961

Colorado

River Basin

18%

5.8 (38 maximum)

U

.S.

Kopp

&

Kroner, 1970

Animas River

45%

2.9 (7.0 maximum)

Cedar NHL

Kopp 6 Kroner, 1970

New Mexico

Colorado River

13.6%

16 (38 maximum)

Loma, Colorado

Kopp & Kroner, 1970

Colorado River

0

ND

Kopp &

Kroner, 1965

Colorado River

0-LO

Yuma, Arizona

Durum & Haffty, 1961

Western Gulf Baran

4.3%

15 (6.6 maximum)

U.S.

Kopp

& Kroner, 1970

Pacific

Northwest Basin

&6 %

0.9 (3.7 maximum)

U.S.

Kopp & Kroner, 1970

Columbia River

0.09-0.15

Near The Danes,

Oregon

Durum & Rarity, 1961

Columbia River

0

0

Kopp & Kroner, 1970

Clearwater

River

0.1

Lewiston, Idaho

1 occurrence

Kopp

& Kroner, 1970

Pend Oreille River

0.2

Albeni Falls

1

occurrence

Kopp &

Kroner, 1970

Dam, Idaho

Snake River

0.5-L3

Payette, Idaho

2 occurrences

Kopp

&

Kroner.

1970

Snake River

1.4

Wawawai, Washington

1 occurrence

Kopp

6

Kroner, 1970

California Basin

0

ND

California

Kopp 6 Kroner, 1970

Sacramento River

0-0.16

Sacramento, California

Durum

&

Haffty, 1961

San

Fernando Valley

20

California

Estimated in

wastewater

Barg

man

6 Garter, 1973

Great Basin

5.3%

0.3

Nevada

1. occlarence

Kopp, 1969

Alaska

5.6%

LI

Alaska

Kopp, 1969

Yukon River

0.20-0.31

Mountain Village,

Alaska

Durum

&

Haffty, 1961

---

Kopp and Kroner (1970) found silver in 6.6 percent of 1,577

surface water samples collected in the United States. Concentra-

tions in samples containing silver varied from 0.1 to 38 pg/1 with

a mean of 2.6 pg/l. The highest silver concentration was in the

Colorada River at Loma, Colorado. Upstream industries included an

old gold-copper-silver mine; an oil shale extraction plant at

Rifle; uranium plants at Rifle, Grand Junction, and

Gunnison; and a

gasoline and coke refinery 1 mile from Loma.

Another striking example of elevated silver concentrations was

found in 280 miles of streams and lakes in the Lower North Canadian

River (LNCR) Basin of Oklahoma. The range of silver concentrations

varied from undetectable to 25 pg/1 in samples collected during all

seasons. Water and sediment samples were collected at eight main-

stream stations, eight tributary stream stations, and four Lake

Eufaula stations. The LNCR also contained extraordinarily high

concentrations of other trace elements and nutrients. The probable

reason for the unusually high silver concentrations was the low

water volume in some of the sampling streams. For example, the

maximum concentration of silver was detected on the Soldier Creek

Tributary (pH 7) which drained wastes from the northeast corner of

Tinker Air Force Base. Silver was never detected at the sampling

station closest to the Henryetta zinc smelter, but even the zinc

concentration was lowest there (Frank, 1969).

Photoprocessing effluents usually

contain Ag(S

203

)

2

-3

'

dis-

sociation

constant 3.5 x 10-14

, Agar solubility product 4.8 x 10

-13

C-8

---

at 25°C or Ag

2

S. Thus, under normal circumstances, they contain no

free silver ions. Municipal biological treatment plants receiving

photoprocessing wastes have not suffered any loss in efficiency

from them. Some photoprocessing plants have even installed bio-

logical treatment plants themselves with up to 5 mg Ag/1 in the

water and 250 mg Ag/1 in the aeration tank sludge. Since silver was

present predominantly as Ag

2

s

with small amounts of metallic sil-

ver, the biological system was not adversely affected. Eastman

Kodak activated sludge plant effluent contained 1 mg Ag/1; no

soluble silver was detected (i.e., '420 pg/1 or 420 ppb).

The Genesee River in New York has received photoprocessing ef-

fluents for approximately 70 years. In 1973, on most sampling

dates from May 31 to October 17, it contained 20 pg/1 silver. How-

ever, levels of 90 to 260 pg/1 were detected in June. Sediments

contained up to 150 mg/kg silver dry weight. Raw Lake Ontario

water at the Eastman Kodak intake pipe contained 1 pg/1 silver

(Bard, et al. 1976).

At 0.04 g Ag/1 and 0.01 g H2B+HS-

per liter, AgSH is the major

silver species normally present in freshwater, being present in

concentrations up to 10-fold greater than the concentration of Ag+

and AgCl. In seawater, there is more AgC12 than AgSH, and Ag+con-

centrations are trivial. Other species of minor or negligible

importance in seawater are AgBr, Ag(SH)

2

, AgF, AgOH, AgI, AgNO3,

Ag(NO2)

2-

, and AgSO4

. The waters are oversaturated with silver by

7 to 12 times what is expected from available thermodynamic data

(Jenne, et al. 1977).

C-9

---

The silver content of natural precipitates (i.e., stream sedi-

ments, etc.) has been discussed by Boyle (1968). The silver con-

tent of U.S. natural precipitates ranges from nil to 1,160 mg/kg.

Turekian found 0.4 to 15.0 mg/kg silver in the suspended matter of

18 U.S. rivers. The Susquehanna River in Pennsylvania, which con-

tained the highest concentration of silver, was estimated to be

transporting 4.5 tons* of silver per year to the ocean (Turekian

and. Scott, 1967).

In the Lower North Canadian River (LNCR), the range of silver

content in the ash of total suspended solids (silt plus micro-

organisms) was from undetected to 0.008 mg/kg, except at the sta-

tion where the highest silver concentration was found in the water.

Here, the silver content ranged from 15 to 50 mg/kg in the ash

(Frank, 1969).

Silver concentrations of 0.05 to 45 pg/1 have been found in

effluents from municipal waste treatment plants. Silver concentra-

tions as high as 900 mg/kg in sewage sludge have been reported

(Smith and Carson, 1977).

Bruland, et al. (1974) studied the extent of metal pollution

in the Southern California Coastal Zone which received Los Angeles

area sewage. The average flux of anthropogenic silver into the

sediments of the California Coastal Basin was estimated to be' 50

percent greater than the average flux of natural silver (0.09

*A mathematical error in the calculations lead to the report itself

stating 45 tons.

C-10

---

versus 0.06 pg/cm

2

/year). The flux of anthropogenic silver to the

sediments

was calculated to be 11 MT/year/12,000 km

2 , with the

chief source being the municipal wastewaters (15 MT/year/12,000

km2),

rather than the storm water plus dry weather flow or the

washout fluxes (1 and 5 MT/year/12,000 km

2

, respectively). Extrac-

tion studies indicated that the silver in these sediments occurred

predominantly as sulfides or bound to the organic phase.

The concentrations of silver in the wastewater particulates

were 32 to 130 (average 70) mg/kg compared with about 6 mg/kg for

the sediments in the basins receiving them. (The sediments were

collected at 75 to 890 m from the sewage outfalls.)

High concentrations of mercury, silver, chromium, and zinc

were recently found in the sediments downstream from the Vint Hill

Farms Station military reservation. Although the sediment contami-

nation extends for two miles in South Run in eastern Fauquirer

County, Virginia, which runs into Lake Manassas, the Manassas water

treatment plant is able to remove the metals because of the water

insolubility of the chemical forms present. There is concern, how-

ever, about heavy metal bioaccumulation in fish (Toxic Materials

News, 1978).

The silver concentration in sediments is important because

bottom-feeding mollusks, etc., tend to concentrate silver. Luoma

and Jenne (1977) in laboratory studies determined that the uptake

of silver, bound to various typical sediment species--by the clam

Macoma balthica, depended on the particular sediment species to

which it

was

bound. The concentration factor for sediment-bound

110mAg

(dry clam tissue/dry sediment) was 3.667 to 6.140 from

C-11

---

calcite; 0.395 to 0.850 from Mn0x

; 0.043 to 0.146 from Fex0y

; 0.034

to 0.076 from biogenic CaCO3

; and 0.028 to 0.030 from organics.

The percent of

110mAg

in the soft tissues of the clam was 42.6 to

57.0 (average 54.4 percent). In these experiments, the sediment-

bound silver contributed somewhat more silver to the clam tissue

than did solute silver (0.034 to 0.552 mg/kg versus 0.004 to 0.135

mg/kg in soft tissues).

Of 380 finished waters, 6.1 percent were found to contain sil-

ver at concentrations varying from 0.3 to 5 pg/1 (mean 2.2 pg/l).

Table 3 shows the silver content of water supplies for several U.S.

cities. The silver content of these water supplies did not exceed

the U.S. drinking water limits for maximum allowable concentration

of silver, 0.05 mg/1 (Kopp, 1969). In another study, the maximum

concentration of silver found in 2,595 distribution samples from

959 public water supply systems was 26 pg/l. The average silver

content found in waters having pH -c= 8 was 0, while for those at pH

> 8.0, the average silver content was 1 pg/l. Of Chicago water

samples, 15 percent showed increased concentrations of silver after

leaving the water treatment plant (McCabe, 1970).*

In 1935, Braidech and Emery reported 0.010 to 0.200 mg/kg sil-

ver (average 0.080 mg/kg) in the solid residues of all 24 city

water supplies they studied. The highest value was from Denver,

Colorado.

*Silver contents in distribution samples (i.e., tapwater) may be

higher than the finished water from the treatment plant because of

the preferred use of tin-silver solders for joining copper pipes in

the home, office, or factory. In addition, American Standard, Inc.

connects copper pipes for hot and cold water with tin-silver solder

during the assembly of kitchen and bathroom appliances (Silver

Institute, 1976b).

C-12

---

TABLE 3

Silver in City Water Supplies

Ag Content (ppb)

Location

Remarks

Reference

0.23 (7.0

maximum)

Cannon & Hopps,

1971

50 (maximum)

U.S.

Maximum allowable Ag con-

tent of drinking water

according to Federal

Kopp & Kroner, 1970

Water Poll. Con. Admin.

8 (average)

30 (maximum observed)

U.S.

2,595 samples of 956

municipal water supplies.

Taylor, 1971

ND - 0.35

Birmingham, AL

Durfor & Becker,

1962

0.09

Mobile, AL

Durfor 6 Becker,

1962

ND -?

0.31

Montgomery, AL

Durfor & Becker, 1962

<0.53 - cz0.92

Phoenix, AZ

Durfor f Becker, 1962

ND - < 0.54

Tucson, AZ

Durfor & Becker, 1962

ND -

?

<. 0.40

Long Beach, CA

Durfor & Becker,

1962

<0.3

Los Angeles, CA

Durfor 4 Becker, 1962

<0.4 -?

<-0.7

Los Angeles, CA

Bergman & Garber,

1973

<0.06

Oakland, CA

Durfor S Becker, 1962

<0.1 -

Sacramento, CA

Durfor f. Becker,?

1962

<0.

78

San Diego, CA

Durfor & Becker,

1962

<0.06 -<:.0.08

San Francisco, CA

Durfor & Becker, 1962

I-•

'4=0.32

ND - <- 0.26

San Jose, CA

Denver, CO

Durfor & Becker,

1962

Durfor & Becker, 1962

0.29

Hartford, CT

Durfor & Becker, 1962

<0.14 - 0.30

New Haven, CT

Durfor S Becker,

1962

<0.25 - <-0.28

Washington, DC

Durfor & Becker,

1962

ND - - 0.49

Jacksonville, FL

Durfor & Becker, 1962

ND -

cz0.50

Miami, FL

Durfor S Becker,

1962

ND -

cz.0.21

St. Petersburg, FL

Durfor & Becker,

1962

0.55

Tampa, FL

Doctor S Becker,

1962

<0.03 - 0.07

Atlanta, GA

Durfor S Becker,

1962

<0.05 - cz0.26

Savannah, GA

Durfor 6 Becker,

1962

'cr-0.26

Honolulu, HI

Durfor & Becker,

1962

0 - 9?

(100%)

Chicago, IL distribution points

McCabe,

1969

0 -

?

1?

(74%)

2 -?

5?

(22%)

(maximum 2 ppb at the treat-

ment plants)

cz0.2 -'0.27

Chicago, IL

Durfor & Becker,

1962

<0.5 - 10.59

Rockford, IL

Durfor 4 Becker,

1962

cz0.29

Evansville, IN

Durfor S Becker, 1962

---

.4%

TABLE 3

(Continhed)

Ag Content (ppb)

Location

Remarks

Reference

0.2 - -c0.54

-cc0.24

ND -

?

0.39

<0.24 -%c10.48

c0.30

-

?

0.3

w‘0.30

- 0.80

<0.25 - 7.0

vr.0.18?

- 0.24

- 0.74

0.18

0.14 - 0.49

0.06

0.21

?

- 0.22

C.0.25 -'0.53

<z.0.23?

- cz.0.25

cz0.15

?

- 0.48

- -cL0.34

0.68

-

-==0.56

<0.22 - c.0.23

0.3

<c0.41

c0.46

CO. 09

0.09?

- 0.38

- 0.09

ND --c.0.5

0.07 - 0.12

0.23 - 0.39

cz0.14 - 0.30

•0.19

0.32?

- cz.0.41

- 0.17

'=.(24.17

ND

0.23

-

c,0.26

1.1

Fort Wayne, IN

Gary-Hobart, IN

Indianapolis, IN

South Bend, IN

Des Moines, IA

Louisville, KY

Baton Rouge, LA

New Orleans, LA

Shreveport, LA

Baltimore, MD

Boston, MA

Springfield, MA

Worcester, MA

Detroit, MI

Flint, MI

Grand Rapids, MI

Minneapolis, MN

St. Paul, MN

Jackson, MS

Kansas City, NO

St.?

Louis, MO

St. Louis, MO

Lincoln, NE

Omaha, NE

Jersey City (contiguous with

Paterson and Newark)

Newark,

NJ

Paterson, NJ

Albuquerque, NM

Albany, NY

Buffalo, NY

New York City, NY

Rochester, NY

Syracuse, NY

Yonkers, NY

Charlotte, NC

Akron, OH

Cincinnati, OH

Cleveland, OH

Columbus, OH

Dayton, OH

Finished Water

Durfor & Becker,

Durfor 6 Becker,

Durfor & Becker,

Darter & Becker,

Durfor & Becker,

Durfor 6 Becker,

Durfor & Becker,

Durfor 6 Becker,

Durfor 4 Becker,

Durfor & Becker,

Doctor & Becker,

Durfor & Becker,

Durfor & Becker,

Durfor & Becker,

Durfor & Becker,

Durfor & Becker,

Durfor 6 Becker,

Durfor 6 Becker,

Durfor & Becker,

Doctor 6 Becker,

Durfor & Becker,

Durfor & Becker,

Durfor & Becker,

Durfor & Becker,

Durfor &

Becker,

Durfor &

Becker,

Durfor & Becker,

Durfor & Becker,

Durfor & Becker,

Durfor & Becker,

Durfor

&

Becker,

Durfor & Becker,

Doctor

&

Becker,

Durfor & Becker,

Durfor

&

Becker,

Durfor & Becker,

Durfor & Becker,

Durfor & Becker,

Durfor & Becker,

1962

1962

1962

1962

1962

1962

1962

1962

1962

1962

1962

1962

1962

1962

1962

1962

1962

1962

1962

1962

1962

1962

1962

1962

1962

1962

1962

1962

1962

1962

1962

1862

1962

1962

1962

1962

1962

1962

1962

---

TABLE 3

(Continued)

Ag Content (ppb)

Location

Remarks

Reference

-c 0.16

<-0.23

0.54 -00.76

Toledo, OH

Youngstown, OH

Oklahoma City, OK

Durfor?

Becker,

Durfor L Becker,

Durfor X Becker,

1962

1962

1962

<0.19 -X0.20

<0.02

<0.26

<0.15 - <0.17

<0.12 - <0.19

0.07

ND - 60.24

ND - 0.19

cO. 16

ND - <0.29

0.15 - c 0.29

ND - < 0.86

ND - <0.15

ND -

?

1.5

<0.27 -00.54

<0.10 - c 0.15

<0.10

0.05 - <-0.06

0.26?

-?0.53

<0.05

<0.5

00 .24 -?

0.25

Tulsa, OK

Portland, OR

Erie, PA

Philadelphia, PA

Pittsburgh, PA

Providence, RI

Chattanooga, TN

Memphis, TN

Nashville, TN

Austin, TX

Dallas, TX

El Paso, TX

Houston, TX

Lubbock, TX

Salt Lake City, UT

Norfolk, VA

Richmond, VA

Seattle, WA

Spokane, WA

Tacoma, WA

Madison, WI

Milwaukee, WI

A well

Durfor & Becker,

Durfor i Becker,

Durfor?

Becker,

Durfor?

Becker,

Durfor?

Becker,

Durfor 6, Becker,

Durfor

?

Becker,

Durfor?

Becker,

Durfor?

Becker,

Durfor?

Becker,

Durfor?

Becker,

Durfor 6 Becker,

Durfor?

Becker,

Durfor i Becker,

Durfor 6 Becker,

Durfor 6 Becker,

Durfor'i Becker,

Durfor?

Becker,

Durfor 6'Becker,

Durfor

?

Becker,

Durfor?

Becker,

Durfor i Becker,

1962

1962

1962

1962

1962

1962

1962

1962

1962

1962

1962

1962

1962

1962

1962

1962

1962

1962

1962

1962

1962

1962

---

In a survey of metal concentrations in the drinking (tap)

waters of Canadian communities, silver was found in 0.1 percent of

the 239 sampled waters (detection limit of neutron activation an-

alysis was 0.001 to 0.005 pg/l) (Neri, et al. 1975).

Tapwater in the Boston metropolitan area contained '

cz. 0.010

mg/1 silver in 896 samples although Cu, Zn, Pb, and Fe were often

present in the soft water of the area due to the corrosion of pipe

materials (Karalekas, et al. 1976).

Silver is used to purify potable water for Swiss ski resorts,

German Breweries, soft drink bottlers, British ships, Shell Oil

Company tankers, drilling rigs, and over half the world's airlines

including Pan Am and American. In the United States, the number of

companies registered by the U.S. EPA to produce silver-containing

water filters grew from 2 to 19 by February, 1978, from 10 only two

years before. At least one water filter has been widely promoted

by television advertising in the United States for home use. The

units of Katadyn Products, Ltd. in Switzerland either produce sil-

ver ions anodically or by the slight dissolution of metallic silver

impregnated on fine-porosity ceramic filters. They have been

approved by the Swiss government for 38 years, requiring less than

200 pg/1 for their antimicrobial action (Silver Institute, 1976a,

1977b, 1978).

The Soviets have found silver ions at concentrations of 100 to

200 pg/1 to be safe, stable, and long-lasting for purification of

polluted water for drinking in the Soviet space ship and orbiting

station program. After animal tests showed these concentrations to

be nondetrimental, year-long human volunteer studies confirmed the

results (Silver Institute, 1973b).

?

Silver sterilizers producing

C-16

---

100 to 200 pg/1 silver ions were also used on the Apollo Spacecraft

waste and potable water systems (Albright, et al. 1967).

Ingestio

n from Food

Silver is a normal trace constituent of many organisms (Boyle,

1968). The ash of higher plants ususally is found to contain

-cz

1

ppm silver, while the ash of terrestrial plants, in general, usu-

ally contains about 0.2 ppm silver. Higher values occur in trees,

shrubs, and other terrestrial plants near regions of silver min-

eralization. Seeds, nuts, and fruits generally have higher silver

contents than other plant parts (Smith and Carson, 1977).

Snyder, et al (1975) estimated that the average intake of sil-

ver by humans is 70 pg/day. Kehoe, et al. (1940) had determined

that daily dietary intake of humans in the U.S. was 88 pg/day. Tip-

ton, et al. (1966) found the average daily intake of silver in the

diets of men and women in the U.S. were 35 pg and 40 pg silver,

respectively. Hamilton and Minski (1972/1973) determined that the

average daily human dietary intake of silver in the United Kingdom

was 27 + 17 pg. No consideration was given to intake from water

used for cooking foods, making beverages, or drinking. Clemente,

et al. (1977) reported that the average silver intake in the diets

of three Italian populations was 0.4 pg/day as determined by neu-

tron activation analysis. Five-day fecal samples of the population

which had a silver intake of up to 7 pg/day showed a range of 1.1 to

202 pg/day (average 30 pg/day). Some source of pollution was felt

to be the cause of greater metal intake. The latter population

came from a large town in central Italy, whose major source of pol-

lution was automotive engine exhaust.

C-17

---

Murthy and Rhea (1968) of the U.S. Public Health Service in

Cincinnati measured, by atomic absorption analysis, 0.027 to 0.054

mg/kg (average) silver in cows milk collected as market samples

from various U.S. cities. The silver content did not vary signifi-

cantly between cities, but there was a significant difference be-

tween quarterly sampling periods in the southeastern states. The

national weighted average was 0.047 + 0.007 mg/kg. Milk from 32

cows on farms serving Cincinnati contained 0.037 to 0.059 mg/kg

silver (average 0.047 + 0.006 mg/kg). Table 4 lists the silver

concentration in several food items.

110mAg

is an activation product produced during nuclear fis-

sion. The concentration factors* from Lichen to caribou or rein-

deer estimated by Hansen, et al. (1966, cited by Garner, 1972) for

110mAg

A

in muscle were 0.3; for liver, 80; for kidney, 1.3; and for

bone, 3. Beattie and Bryant (1970) had estimated that 15 percent

of the total

111Ag

dose from activation products would be received

in a 30-year period starting in infancy by the forage-cow-milk

pathway.

Sewage-sludge amended soils may have 10 times or more silver

than normal and may increase human intake of silver by its incor-

poration into food crops in greater than normal amounts. Silver

uptake by plants appears to be directly related to its soil concen-

tration (Cooper and Jolly, 1969). Addition of phosphate to soil

contaminated with silver, however, reduces its plant availability

(Dawson, 1974).

*Ratio of

110mAg

activity per unit wet weight of tissue activity

per unit wet weight of lichen.

C-18

---

TABLE 4

Silver in Some Foods

Type of Food

?

Silver Concentrations, mg/kg

?

Reference

Beef

Beef liver

(SAM 1577)

Pork

Mutton and lamb

Milk powder

Potato powder

Sugars

Brown (Barbados)

Demerara

Refined

Granulated

Mollusks

Crustaceans

Trout (Lake Cayuga,

New York)

Mushrooms

Wheat (Triticum spp.)

Bran

Flour

Coffee beans

Tea (Camellia sinensis)

0.004-0.024

0.005-0.194 (same sample

by three laboratories)

0.007-0.012

0.006-0.011

0.010 + 0.04

0.015

T

0.005

0.03

0.004

0.001

0.002

0.1-10.0 (dry weight)

2.0 (dry weight)

0.48-0.68 (dry weight)

"Up to several hundred"

(dry weight)

0.5 (dry weight)

1.0 (dry weight)

0.4 (dry weight)

0.02 (dry weight)

0.20-2.00 (dry weight)

Armour Research

Foundation, 1952;

Mitteldorf and

Landon, 1952

Masironi, 1974

Armour Research

Foundation, 1952

Armour Research

Foundation, 1952

Schelenz, 1977

Schelenz, 1977

Hamilton and

Minski, 1972/1973

Boyle, 1968;

Cooper and Jolly,

1970

Boyle, 1968

Tong, et al. 1974

Cooper and Jolly,

1970

Kent-Jones and

Amos, 1957

Vanselow, 1966

Vanselow, 1966

---

It is possible that the silver content would be increased in

the meat of animals pastured or fed grains raised on contaminated

soils.* At least one study, however, has indicated that the trans-

fer of iron, copper, nickel, chromium, zinc, cadmium, and lead from

sewage-sludge amended soils to dairy or beef cattle milk or tissues

is minimal (Nelmes, et al. 1974).

Among aquatic species harvested for food, the heptopancreas

and nephridial organs of brachiopods, molluscs, and arthropods,

particularly crustaceans, accumulate heavy metals. The glandular

tissue of the liver of fish and all other vertebrates concentrates

metals (Vinogradov, 1953). Marine animals accumulate silver in

concentrations which are higher than their environment. Clams and

scallops growing near municipal sewage-sludge dumping sites accumu-

late higher concentrations of silver than do those growing where

the concentrations of silver are lower (Toxic Materials News,

1975). The enrichment factor calculated by Noddack and Noddack

(1939) for silver in marine animals over seawater is 22,000. A

bioconcentration factor is not estimated from the value since these

data are not purported for indigenous species. The dead bodies of

animals in reducing environments will contribute their silver to

sediments, a major factor in the biogeochemical cycle of silver

(Boyle, 1968).

Besides food and drinking water, silver is possibly ingested

from dissolution of silver dental amalgams in the mouth by saliva.

Wyckoff and Hunter (1956) qualitatively detected silver spectro-

*If a 0.25-lb portion of meat contains 0.007 mg/kg, the 0.0065 mg

silver consumed would represent only about 1 to 2 percent of the

low silver dietary intake reported by Tipton, et al. (1966).

C-20

---

graphical

ly

in the erythrocyte contents and possibly in the plasma

and erythrocyte membrane (ghosts) of two people who had dental

filling

s. No silver was detected in a preliminary examination of

another person who did not have any dental fillings. Reynolds and

Warner (1977) concluded that the corrosion product of Ag

3

Sn amal-

gams after only 30-minute exposure to human saliva in

vitro was

SnC14.

Some silver may be released to soft tissues from silver amal-

gam dental fillings when placed in unlined cavities according to

Leirskar (1974), who found by atomic absorption analysis that there

was definite release of zinc and mercury into a human monolayer

epithelial cell culture (22 pg Zn/ml and 0.0177 to 0.0196 pg

Hg/ml); some silver also appeared to have been released. Silver

amalgam cultures contained 0.02 pg Ag/ml after three days. (The

detection limit for silver, however, was 0.01 pg/m1--much higher

than that for mercury.) Leirskar cited three other studies that

reported diffusion of amalgam constituent metals, including silver,

into adjacent dentin.

Inhalation

Silver is generally a very minor constituent of ambient aero-

sols. Table 5 gives a reasonably representative sample of silver

determinations in air, although it is by no means exhaustive, since

reports of nuclear activation analyses of atmospheric particulates

are proliferating rapidly. Interestingly enough, Chadron,

Nebraska, which has a population of 6,000 in a sparsely inhabited

region, had the same average ambient air concentration of silver in

1973--0.15 ng/m

3

--as San Francisco had in 1970. A nonindustrial

C-21

---

TABLE 5

Silver in Ground-Level Atmospheric Aerosols 6,7

City

?

Date

Aerosol. Silver Concentration

ng/m3?ppb

Reference

Heidelberg,

Germany

Niles, MI

Northwest

IN

East Chicago, IL

Chicago, IL

Oak Ridge, TN

Vicinity:

Walker Branch

Watershed

Chadron, NE

April -

June, 1971

June, 1969

1969

June, 1969

1968

July, 1974

1973

Bogen, 1974

Bogen, 1974

Dams, et al. 1971

Bogen, 1974

Brar, et al. 1970

Andren, et al. 1974

Struempler, 1975

4.2

?

0.0032

1

?

0.00077

1.5

2.4

?

0.0019

4.3

0.17

?

0.00013

average 0.15

(range 0.02

to 1.8)

0.14

Washington, DC

June -

Sept. 1973

June -

Sept. 1974

1974

San Francisco, CA

?

1970

?

0.15

Kellogg, ID

(city hall)

10.5* (range

0.936 to 36.5)

Trout, 1975 cited by

Greenberg, et al. 1978

John, et al. 1973

cited by Greenberg,

et al. 1978

Ragaini, et al. 1977

0.04

1.1

*Average Concentrations of mercury, antimony, cadmium, zinc, and lead ranged from

10,800 ng/e. The nearby Bunker Hill smelter smelts silver-rich lead concentrates and

zinc concentrates.

113 to

roasts

---

city, Washington, D.C., had a concentration of 1.1 ng/m 3

in 1974.

The very industrialized urban environment of Chicago, Illinois, had

an ambient atmospheric silver concentration only four times higher

(4.3 ng/m3).

Even one of the sites having an expectedly high sil-

ver concentration in the silver-rich Coeur d'Alene region of

northern Idaho had only an order of magnitude greater silver con-

centration (average 10.5 ng/m

3

) than a nonindustrialized large

population center.

Smith and Carson (1977) estimated that total annual atmos-

pheric silver emissions in the United States in the early 1970's

were about 340 short tons or about 310,000 kg. About 60 percent of

this total was distributed equally between iron and steel produc-

tion and cement manufacture, about 12 percent each was due to

fossil fuel burning and nonferrous metal smelting and refining, and

about 7 percent was due to urban refuse incineration. Another

published estimate for total annual silver emissions was 417 short

tons (Dulka and Risby, 1976, citing a personal communication from.

V. Duffield, 1975).

Greenburg, et al. (1978) attributed to urban refuse incinera-

tion a much higher share of the total silver content in the urban

particulate load. They estimated that the contribution of silver

from refuse incineration to ambient urban air is 1.7 ng/m3 .

Steel mills have been implicated as the major source of aero-

sol silver, yet the following data (Harrison, et al. 1971) do not

seem to support this contention. Air particulate samples were col-

lected on June 11 and 12, 1969, at 25 stations in the northwest

Indiana area, including the Hammond-East Chicago-Gary-Whiting

C-23

---

metropolitan complex. At that time, the entire sampling area con-

tained three large steel mills, as well as four large petroleum

refineries, foundries, steel fabricators, chemical plants, a large

cement-manufacturing plant, and two large power utilities. The

silver concentrations in the area ranged from 0.5 to 5 ng/m3

. The

maximum silver concentration was found at a station downwind from

the steel mills. High silver concentrations did not occur at the

same stations where maximum iron levels occurred. Therefore, steel

manufacturing was not believed to be the major source of silver

found in these samples (Dams, et al. 1971).

At another station, in Gary, near the third steel mill,

secondary maxima for iron and eight other metals were associated

with a silver concentration of 4 ng/m3

. The direction of the unus-

ually strong, steady wind prevailing during the sampling was such

that most of the shoreline steel and cement plant emissions (■...85

percent and 12.5 percent, respectively, of the area's industrial

particulate emissions) may have been swept directly over the lake

so that the observed air concentrations at stations nearest them

were much lower than normal (Dams, et al. 1971). On April 4, 1968,

one day after general rainfall, with wind blowing at 34 km/hr, the

silver concentrations in surface air samples from 22 aerosol-

collecting stations in Chicago, Illinois, ranged from 0.18 to 7.0

ng/m3

(average 4.3 ng/m3

). Correlation coefficients for silver

with other elements or dust were not determined (Brar, et al.

1970).

Another source of silver to ambient air is from volatile emis-

sion from certain trees. Curtin, et al. (1974/1975) traced the

C-24

---

path of elements from the soil and mull (the humus-rich layer of

mixed organic and mineral matter 3 to 8 cm thick beneath individual

trees) into the needles, twigs, and volatile exudates of Lodgepole

pine, Engelmann spruce, and Douglas fir in Idaho Springs, Colorado

and Stibnite, Idaho. Silver was not detected in the soil; but in

Colorado, its highest concentrations were in the mull ash under all

species. In Idaho, the silver concentration was highest in the

twigs of the pine and spruce and in the exudate residue of the Doug-

las fir. Presumably, the metals in the exudate are complexed by

terpenes and appear in the blue haze of forested areas.

Nadkarni and Ehmann (1969) measured 2.61 mg/kg silver in a

reference cigarette tobacco* by neutron activation analysis and

2.87 mg/kg silver in the paper. Nadkarni, et al. (1970) found 0.27

+ 0.18 mg/kg silver in a filter cigarette of a popular brand and

0.18 + 0.03 mg/kg in a nonfilter cigarette of the same brand; there

was 0.48 mg/kg silver in 1.65 g of smoke condensate from 500 filter

cigarettes and 0.30 mg/kg silver in 14.5 g condensate from 500 non-

filter cigarettes. Only 0.60 percent of the silver transferred

into the mainstream smoke condensate of the filter cigarette; 4.4

percent transferred from the nonfilter cigarette. The amount of

silver inhaled into the lungs in the mainstream smoke per cigarette

would be negligible according to these data: 8.7 ng per nonfilter

cigarette and 1.6 ng per filter cigarette.

*A blend of four major tobacco types: flue-cured, Burley, Oriental,

and Maryland. The nonfilter cigarette dimensions were 85 mm in

length, 25 mm in circumference.

C-25

---

Exposure from cloud-seeding operation may be significant only

to a ground-based generator operator.* Standler and Vonnegut

(1972) estimated the concentration of silver (0.1 pm particles) in

air downwind in the target area from a ground-based silver iodide

cloud-seeding generator is 0.1 ng/m3

, a factor of 105

below the

maximum allowable concentration in workplace air. At the generator

site itself, however, exposure exceeds the maximum permissible con-

centration within 50 m downwind of the generator. Seven cloud-

seeding operators with extensive exposure to silver iodide knew of

no persons who had experienced any ill effects due to silver

iodide, despite the fact that their hands may remain yellowed for

weeks. Vonnegut, however, recalled a technician in New Mexico in

the early 1950's who claimed the aerosol from a ground-based gen-

erator aggravated his respiratory allergy, and Douglas had reported

in 1970 a skin rash developing in an individual who had been within

a few meters of an operating generator for six hours. Inhaling the

acetone vapors from the unignited silver iodide solution is of more

concern to some operators.

The Occupational Safety and Health Administration (OSHA) stan-

dard for silver metal and soluble compounds in the workplace air is

0.01 mg/m3

for an 8-hour time-weighted average (39 FR 23541).

According to the American Conference of Governmental Indus-

trial Hygienists (ACGIH, 1977), the Threshold Limit Value-Time

Weighted Average (TLV-TWA) for aerosol silver metal or soluble

silver compounds as metal is 0.01 mg/m

3

. The tentative value for

*Bernard Vonnegut in 1947 in General Electric Laboratory experi-

ments, showed that silver iodide crystals can initiate ice crystal

formation (Fleagle, et al. 1974).

Ii

C-26

---

the Threshold Limit Value-Short Term Exposure Limit (TLV-STEL) is

0.03

111

9/m3

. The TLV-TWA is based on a normal 8-hour workday or 40-

hour work week, day-after-day exposure. The TLV-STEL is defined as

the maximum concentration to which a worker may be exposed continu-

ously for as long as 15 minutes without irritation, chronic or

irreversible tissue changes, or sufficient narcosis to increase

accident proneness, self-rescue, or work efficiency. Up to four

such excursions may occur per day provided at least 60 minutes

elapse between such exposures and provided the TLV-TWA was not ex-

ceeded in the time lapses.

The ACGIH (1971) stated that, "If one assumes a 20-year expo-.

sure, a 10 m3/day*

respiratory volume, and a 50 percent body reten-

tion, a level of silver fivefold the recommended TLV (0.05 mg/m3)

will result in an accumulation of 1.2 g or a probable borderline

amount for the production of argyria."** The problem of how ab-

sorption of metallic silver from the lungs might parallel direct

injection of silver compounds into the bloodstream was not dealt

with.

More pertinent information with regard to a TLV for silver in

air was supplied to the ACGIH by Fassett in a personal communication

(undated and unidentified as to organization). After observing

silver workers for many years, he believed that silver concentra-

tions of 0.01 mg/m3 in workroom air are unlikely to cause argyria.

* Presumably, for the work day. Snyder, et al. (1975) estimated a

23 m

3

/day respiratory. volume.

**The reference is somewhat in error in stating that the gradually

accumulated intake of from 1 to 5 g Ag will lead to generalized

argyria. The values given by Hill and Pillsbury (1939) are 0.91 to

7.6 g, given i.v.

C-27

---

Jindrichova (1962, cited by ACGIH, 1971) had observed 12 cases of

argyria resulting from exposure to workroom air concentrations of 1

to 2 mg/m3

in the processes of manufacturing silver varnish and its

use in silvering radio-technical parts.

Winell (1975) compared the hygienic standard for chemicals in

the work environment for which both the United States and the USSR

had standards. Since silver was not included, apparently the USSR

does not have a limit for silver. Argentina, Great Britian, Nor-

way, and Peru apply the U.S. standards.

Occupations where silver inhalation is still possible include

silver polishers and occupations involved in melting silver or its

low-melting alloys (e.g., tin-silver solder for copper plumbing).

The silver nitrate manufacturers and packers were the most frequent

victims of generalized argyria according to Harker and Hunter

(1935), but the processes have been obsolete for decades.

Silver polisher's lung was first described in 1945. The dust

inhaled contains both iron oxide (rouge) and metallic silver. The

latter stained the tissue black (Aponte, 1973). Argyria was seen

less often in pourers of molten silver than in silversmiths engaged

in filing, soldering, polishing, engraving, etc. But, according to

Lewin (1896), it was always localized rather than generalized as

would occur from inhalation. Yet Koelsh (1912) (both references

cited by Harker and Hunter, 1935) found that two men whose occupa-

tion involved cutting up thin sheets of silver had generalized pig-

mentation and suggested it was due to inhalation or ingestion of

the workplace dust (300 mg silver/kg dust).

C-28

---

In the melting area at the San Francisco mint on December 24

to-27,

1972, the Industrial Hygiene Services Branch of the National

Institute for Occcupational Safety and Health (NIOSH) determined

0.01 to 0.04 mg/m3 of silver fumes in the air (average 0.02 mg/m3;

the threshold limit value of 0.01 mg/m3 was exceeded in seven of

the eight samples). The melting and casting operations caused

smoke and fumes throughout the melting room despite adequate venti-

lation over the melting area (Anania and Seta, 1973). Although

silver is seldom encountered in new U.S. coinage except for the

special silver-containing editions of U.S. Eisenhower dollars made

only at the San Francisco mint from time to time, such information

is probably applicable to the extent of occupational exposure at

firms that make medallions, silver bars, and other commemorative

items of case silver. Sterling silverware and holloware are gener-

ally manufactured without melting operations. Silver platers are

more at risk from cyanide poisoning rather than silver poisoning.

Dermal

Laws in many states still require that a few drops of a 1 or 2

percent silver nitrate solution be applied to the conjunctiva of

the eyes of newborn infants to prevent ophthalmia neonatorum by

transmittal of gonorrhea from the mother (Martin, 1965). Use of

silver nitrate is a legal requirement in Denmark, but it is not

used in Japan or Australia.?

Elsewhere, there is a free choice

between silver nitrate and antibiotics. Silver nitrate is no

longer used in 20 percent of U.S. hospitals because of the dangers

of chemical conjunctivitis (Shaw, 1977).

C-29

---

In the U.S., several silver-containing pharmaceuticals for use

-on

skin or mucous membranes can be obtained; some do not need a

prescription. Among the medications are Argyro0(mild silver pro-

tein) and Protargol!) (strong silver protein), Neo-SilvolD (col-

loidal silver iodide in a gelatin base), silver nitrate, and Silva-

den

g)(silver

sulfadiazine) (Pariser, 1978);

The risk of argyria from silver-containing topical medicinals

continues today. Marshall and Schneider (1977) reported a case of

systemic argyria which had first begun to appear by November, 1971

in a 46-year-old woman. She had begun using silver-nitrate appli-

cators for bleeding gums from ill-fitting dentures, upon the advice

of her dentist. From April, 1970, she had used three applicators

per week and continued using them even after the first bluish dis-

coloration appeared about her nose and forehead. By July, 1972,

she was already strikingly pigmented, was diagnosed as having

argyria, and was advised to discontinue use of the applicators. In

1973, the pigmentation of her abdominal organs was noted during an

exploratory laparotomy. None of the patient's physical ailments

was attributed to the use of silver nitrate.

Moyer and his associates instituted the use of hypotonic sil-

ver nitrate burn treatment in April, 1964, at Barnes Hospital in

St. Louis, Missouri. It was discontinued there in December, 1967.

Monafo had developed colloidal silver isotonic solutions, and

Margraf and Butcher had developed other silver salts in ointment.

In the opinion of Monafo and Moyer (1968) of St. John's Mercy

Hospital in St. Louis, "Because most salts of silver, other than

the nitrate, are insoluble..., it was predicted that due to preci-

C-30

---

pitation

at the wound surface, little or no absorption of silver

would occur through burn wounds. It was, therefore, anticipated

that systemic toxicity would be inconsequential. Moreover, argy-

ria, the slate-gray discoloration of the skin that results from the

ingestion or absorption of silver is innocuous physiologically and

does not shorten life." No patient had developed argyria, but sil-

ver was detected in plasma and urine. Patients with extensive

burns treated for up to 80 days had 0.05 to 0.30 mg silver per liter

in their plasma.

Hartford and Ziffren (1972) reported on the results of 0.5

percent silver nitrate use on the dressings of 220 burn patients.

Compared with the rate in the 1950-1960 decade, mortality had been

dramatically reduced. By the late 1960's, the search for a less

soluble but effective silver compound lead to the synthesis (by

C.L. Fox, Jr.) and clinical trials of silver sulfadiazine.

Silver sulfadiazine, by 1974, according to Fox (1975), had

been used in the treatment of more than 10,000 burn patients in

many countries for more than seven years. It had been approved by

the regulatory agencies in the United States and the United Kingdom

so that more general use had begun (Silver Institute, 1977a).

Less than 10 percent of the sulfadiazine is absorbed, and far

less of the silver. Daily treatment of 1 m2

of burn surface (a 50

percent burn in an adult) requires 200 g AgNO3

(127 g Ag) (40 liters

of 0.5 percent solution) or 4 g silver sulfadiazine (1.2 g Ag) (one

400 g jar of 1 percent cream or lotion). Fewer than 10 of 10,000

patients showed any drug sensitivity (Fox, 1975).

C-31

---

A 1 percent silver cream made of silver nitrate, zinc sulfate,

and allantoin has been developed for self-care treatment of cuta-

neous ulcers. In a study of 400 chronic skin ulcers in 264

patients, 84.5 percent were completely healed within 3 to 40 weeks

(10 weeks average) (Silver Institute, 1977c). The compound is

another slow-release form of silver and is less likely to produce

argyria than silver nitrate preparations alone.

Silver nitrate hair dyes have been used regularly since about

1800. Sodium thiosulfate developers are added to the hair first,

followed by 0.5 to 15 percent silver nitrate solutions containing

various amounts of ammonia to 'give gradations of shade. The 5 per-

cent solution with ammonia is widely used to dye eyebrows and eye-

lashes and is the only colorant commonly used for the purpose in

the U.S. (Wall, 1957, 1972). At least one case of argyrosis has

been reported from such use. An Italian physician who dyed his

eyebrows, moustache, beard, and eyelashes with a silver dye for 25

years developed argyria in the conjunctiva of both eyes (Wall,

1957).

Several swimming pools in the U.S. are equipped with filtering

systems of activated carbon of very high surface area coated with

pure metallic silver. The effective water concentrations of silver

ions are 20 to 40 ug/1 (Silver Institute, 1973a,c, 1974, 1976c).

Dermal absorption of silver from swimming pools is not expected,

although absorption through the conjunctiva is possible. Although

evidence is cited later in this document that mucous membranes and

C-32

---

wounds allow absorption of silver compounds to an unknown extent,*

very little, if any, ionic silver is absorbed by intact skin.

PHARMACOKINETICS

Absorption

Silver may enter the body via the respiratory tract, the gas-

trointestinal tract, mucous membranes, or broken skin. Some re-

ports even claim absorption through intact skin. In most cases of

argyria, caused by occupational exposure, absorption has been via

the respiratory tract or the conjunctiva (Hill and Pillsbury,

1939). Up to 10 percent of a single oral dose of silver is ab-

sorbed. The literature data do not lend themselves to a ready cal-

culation of the degree of absorption after inhalation or dermal

exposure. Absorption from even nonintact skin appears to be much

less than 1 percent.

Rats ingesting 1.68 g/kg of colloidal silver for 4 days or

0.42 g/kg for 12 days showed higher silver concentrations in the

lungs than in the liver. Based on distribution studies described

in the following discussion, the amount found in the lungs is so

high that perhaps the rats aspirated part of the dose. Otherwise,

the total amount of silver recovered in the heart, lungs, kidney,

spleen, liver, and muscles would indicate that at least 2 percent

of the higher dose (if one assumed the average rat weighed 200 g)

was absorbed. Apparently, almost 5 percent of the silver was

absorbed at the lower dose (Dequidt, et al. 1974).

*That is, the percent of the total dose absorbed has not been cal-

culated; however, long-term use of the topical silver medicinals

(generally silver nitrate) for mucous membranes has certainly led

to argyria.

C-33

---

Scott and Hamilton (1950) concluded that rats absorbed 0.1

percent of a carrier-free dose of radiosilver upon ingestion.*

Rats were given the doses intragastrically. Four days after the

dosing, 99.0 percent of the original dose had been eliminated in

the feces and 0.18 percent in the urine; yet the tissue distribu-

tion apparently totals 0.835 percent; 0.52 percent in the lungs,

0.025 percent in the blood, 0.11 percent in the G.I. tract, 0.034

percent in the skin, and 0.076 percent was in the balance remaining

after the other internal organs, bones, and muscles revealed no

silver.

Dogs (four male beagles, average 5.5 years, 12 to 16 kg) were

presumed to absorb 10 percent of oral doses of 0.6 uCi

110Ag

as the

nitrate since only 90 percent was lost very rapidly (Furchner, et

al. 1966b).

Three rabbits inhaled an aerosol of 10 percent colloidal sil-

ver solution for eight hours (Kondradova, 1968a,b) and were immedi-

ately sacrificed. In the tracheal epithelium, silver had accumu-

lated in the large vacuoles in the cytoplasm of epithelial cells.

In a human who had accidentally inhaled 110m Ag, most of the

inhaled silver had a biological half-life of about one day, prob-

ably due to rapid mucociliary clearance, swallowing, and fecal

excretion. By whole-body counting on the second day, silver activ-

ity was seen in the liver, which indicated some absorption although

*Furchner, et al. (1966b) state that the findings of the Scott

and Hamilton report indicate about 4 percent absorption from

the gastrointestinal (G.I.) tract.. They found that mice absorbed

less than 1 percent.

C-34

---

the published data do not permit a calculation of absorption (New-

ton and Holmes, 1966). Newton and Holmes believed colloidal forms

of silver are the species of silver absorbed in the lungs and that

phagocytosis would account for the localization in the liver. They

cited a study by Hahn and Corrothers (1953) in which the radio-

silver coating of colloidal gold particles administered intrabron-

chially to dogs was gradually leached off in the lungs and appeared

in the liver.

West, et al. (1950) reviewed early investigations into cuta-

neous absorption of silver. Muller, in a privately printed 1936

report cited in Hill and Pillsbury (1939), stated that all of the

silver oxide in a 5 percent oily dispersion was absorbed after

topical application to intact skin, wounds, or mucous membranes.

He found no silver deposits in the skin or underlying tissue, but

he claimed to have accounted for 73.1 to 88.5 percent of the silver

administered to four guinea pigs in their excreta within 31 days of

the inunction of their intact skin. Win (1887) could find no per-

manent deposit of silver granules six weeks after their dermal

injection. Jacobi (1878) could not produce generalized argyria,

however, by s.c. injections of

a

silver solution in rabbits; yet

Pincussen and Roman (1931) found silver in blood, skin, kidney,

spleen, and liver after s.c. injection of silver sulfate in rats.

West, et al. (1950) citing unpublished data of West, Elliott, and

Hahn, found activity in many organs and feces of albino rats after

s.c. injections of a mixture of

108Ag

and 110Ag.

C-35

---

Hill and Pillsbury (1939) reviewed several studies in which

silver was apparently not absorbed from intact skin. The Muller

study was described in a footnote.

The depilated backs of rats were painted daily with a satu-

rated solution of Collargo/F) (colloidal silver and silver oxide)

for three months. By atomic absorption spectrometry and colori-

metry, traces of silver were found in the heart and lungs, 1.54

mg/kg in the kidney, 1.50 mg/kg in the spleen, and 0.16 mg/kg in the

liver (Dequidt, et al. 1974).

Wahlberg (1965) determined that the absorption of silver

nitrate from a solution containing 25.8 g Ag/1 by the intact skin

(3.1 cm2) of guinea pigs was less than 1 percent five hours after

topical application.

Argyria was relatively common following use of silver prepa-

rations as applications to the mucous membranes according to Hill

and Pillsbury (1939), but the argyria was usually described as

"local" rather than "generalized," which would indicate systemic

absorption.

Marshall and Schneider (1977), however, have described a rare,

present-day case of generalized argyria due to assiduous use of a

silver nitrate stick for bleeding gums due to ill-fitting dentures.

Applications of silver nitrate dressings to open wounds allows

systemic absorption of silver. Constable, et al. (1967) treated

open wounds (3.5 x 3.5 cm2)

on the backs of guinea pigs with 0.5

percent AgNO3

solution for five days. In Table 6, the range of sil-

ver concentrations in the organs of four or five topically treated

guinea pigs are compared with those in one guinea pig drinking the

C-36

---

TABLE 6

Comparison of Tissue Distribution after Dermal Gastro-

Intestinal

Absorption of Silver from a 0.5 Percent AgNO

3

Solution*

Concentration, mq/kg

Organ

?

Dermal Route

?

Gastrointestinal Route

Skin

3.0-35.5

1.5

Skin by wound

42.5-3,491.1

Ulcer

2.0-6,649.5

Liver

15.2-29.6

35.3

Bile

0.5-1.8

0

Kidney

7.6-152.0

2.1

Lymph node

1.8-14.4

2.8

Stomach

2.2-24.9

164.8

Intestine

3.8-38.0

10.0

*Source: Constable, et al. 1967.

C-37

---

0.5 percent AgNO3

solution (probably not the same amount as re-

ceived by topical treatments). Loss of silver from the liver was

fairly rapid after cessation of treatments. After one week, <.40

percent remained and after two weeks,c25 percent. Since the AgNO3

contained some

111Ag

(t

1/2

= 7 days), radioautographs showed that

silver was concentrated in the Kupffer cells and around the bile

canaliculi with very small amounts in the glomeruli and most in the

kidney in the cells lining the renal tubules.

Bader (1966) analyzed the organs of two burn patients who had

been treated with fresh dressings of silver nitrate continuously

for at least six days or for every 8 hours for 30 days. In the 66-

year-old man, who had died of a brain tumor about 50 days after the

8-hour treatment was initiated, the silver concentrations in the

tissues were slightly above normal:

?

bone, 0.025 mg/kg; heart,

0.040 mg/kg; kidney, 0.140 mg/kg; and skin, 2,800 mg/kg. The

second patient was an 18-year-old male, who died of respiratory

complications on his 7th hospital day. Before death, the silver

concentration in his urine was 0.038 mg/1 and in his blood, 0.12

mg/l. There was no silver detected in his lungs or brain; but the

concentrations in other tissues were: heart, 0.032 mg/kg; kidney,

0.14 mg/kg; spleen, 0.23 mg/kg; liver, 0.44 mg/kg; muscle, 2.0

mg/kg; and skin, 1,250.0 mg/kg. On the basis of information of Fox

(1975), the daily dose of silver from silver nitrate dressings is

127 g. The patient dying on the 7th day was probably treated for at

least six days, receiving 762 g silver. On the assumption that his

body weight and the weight of his organs were those of reference

man (Snyder, et al. 1975) and with the exclusion of the silver

C-38

---

content of his skin, one can calculate that the organs named con-

tained 57.5 mg silver. Because the silver concentration of his

liver and heart were approximately the same as those of the older

man, we will assume that his bones had the same silver content, 0.9

mg. These values plus his urinary output for at least one day (cer-

tainly no more than 0.04 mg and probably less because of possible

renal impairment), total 58.44 mg or 0.008 percent of the 762 g

dose of silver.

Silver sulfadiazine has very low water solubility and probably

• remains in the wound exudate according to Nesbitt and Sandman

(1977• The solubility in distilled water cannot be detected by

any potentiometric method. At pH 3.851 with a nitric acid buffer,

ionic strength 0.1 M, the solubility of Ag+

was about 6.5 x 10-5 M;

at pH 2.128, about 60 x 10

-5

M. Yet, Wysor (1975a), citing a Marion

Laboratories brochure on Silvaden0) dated March 1, 1972, stated

that very large concentrations of silver sulfadiazine applied topi-

cally has caused silver deposition in the kidney basement membrane.

Wysor (1975a) gave CF

I.

mice, infected with Plasmodium berghei, oral

doses of 1,050 mg/kg of various silver sulfonamides for five days.

Only silver sulfadiazine proved effective in curing the mice of

their malaria; presumably, it was solubilized and absorbed.

Dermal absorption of silver sulfadiazine from wounds is low.

In clinical trials with silver sulfadiazine cream, Fox, et al.

(1969) reported that when 5 to 10 g of the drug was applied to the

burned surface of 31 patients, the levels of sulfadiazine in the

blood were 10 to 20 mg/1 and there was 60 to 300 mg/1 in the urine

(24-hour excretion of 100 to 200 mg). When burned guinea pigs were

C-39

---

treated with radioactive silver sulfadiazine, Fox, et al. (1969)

did not detect any radioactivity in the organs or blood.

Moncrief (1974) reported that 10 percent of the sulfadiazine

of silver sulfadiazine applied to burns is absorbed to give blood

levels of 15 to 40 mg/1, peaking 3 to 4 days after initiation of

treatment. The daily absorption rate decreases during the first 10

to 15 days after the initiation of therapy. Radiosilver does not

appear in the blood from silver sulfadiazine; but when silver

nitrate soaks are used, there is 0.05 to 0.3 mg/1 silver in the

plasma.

Burke (1973) compared the excretion of silver by children and

adults, untreated and treated with silver sulfadiazine. His re-

sults are in Table 7.

Distribution

The amount of silver administered, its chemical form, and the

route by which it is administered affect the tissue content and

distribution of silver within the body (Furchner, et al. 1968).

It is retained by all body tissues. The primary sites of deposi-

tion in persons who have never taken silver therapeutically are the

liver, skin, adrenals, lungs, muscle, pancreas, kidney, heart, and

spleen. Silver is also deposited in blood vessel walls, testes,

pituitary, nasal mucous membrane, maxillary antra, trachea, and

bronchi (Sax, 1963). Although silver does not accumulate in the

lungs with age, it was present in 39 percent of the lungs from

Americans analyzed by Tipton and Cook (1963). Examinations of

accidental death victims indicated that the silver content of the

myocardium, aorta, and pancreas tended to decrease with age (Bala,

C-40

---

TABLE 7

Silver Concentrations in Human Blood and Excreta*

(mg/kg)

Blood

Urine

Feces

0.75

0.73

3.2

0.13

0.12

19.3

0.09

0.02

1.0

0.05

0.003

0.53

7.0

6.0

2.0

0.21

subject

Patient with 70 percent

•?

burns, treated with silver

sulfadiazine for 1 month

Same

patient, 2 months

later, after grafting

Patient with 60 percent

burns, treated with silver

sulfadiazine for

3 months, off treat-

ment for 1 month

Control adult

Child with 15 percent

burns, 11-months-old

(length of silver treat-

ment not given)

Control child

*Source: Burke, 1973

C-41

---

et al. 1969). Silver accumulates in the body with age, however,

even if none is administered intentionally (Hill and Pillsbury,

1939).

A striking feature of argyria is the regular deposition of

silver in blood vessels and connective tissue, especially around

the face, conjunctiva, hands, and fingernails (Hill and Pillsbury,

1939). The silverbearing particles in one case of localized argy-

ria of a photoprocessor were found to be silver sulfide (Ag2S),

possibly contained in the mitochondria (Buckley, et al. 1965). The

silver-containing particles were sparsely distributed at the dermo-

epidermal junction of the papillary bodies adjacent to the epi-

dermal portion of the sweat ducts. The silver had entered the skin

via the sweat glands (Buckley, 1963).

In argyria, aside from the blood vessels and connective tis-

sues, the dermis of the skin, glomeruli of the kidney, choroid

plexus, mesenteric glands, and thyroid contain the greatest amounts

of deposited silver. The epithelium is free of silver deposits

(but Buckley, et al. 1965, report that silver ions are present

there).* Other tissues where deposition may occur include: bone

marrow, pancreas, liver, spleen, testes, and ovaries (Hill and

Pillsbury, 1939; Sax, 1963; Van Campen, 1966).

?

The adrenals,

*According to Lever (1961) in the 3rd edition of Histopathology of

the Skin, in argyria, silver is found in the dermis--chiefly out-

side the cells, as uniformly sized particles ("...fine, small

round, brownish...")--but never the epidermis. The particles, ly-

ing singly or in clumps, are -c111 in diameter. "Under a dark-

field microscope, the silver appears as brilliantly refractile,

white granules against a dark background." Melanin and hemosi-

derin granules are larger, largely intracellular, and nonrefrac-

tile on dark-field illumination.

C-42

---

rungs, dura mater, bones, cartilage, muscles, and nervous tissue

are minimally or never involved as deposition sites for silver

(Hill and Pillsbury, 1939). Exposed skin shows greater amounts of

melanin in the dermis and epidermis. Robert and Zurcher (1950,

cited by Lever, 1961), had stated that silver favors melanin forma-

tion by increasing oxidative processes. Silver is especially

deposited in intima of blood vessels and connective tissue of

internal organs. Basement membranes around the acini of the testes

and of the choroid plexis are rich in silver granules (Harker and

Hunter,

1935).

Polachek, et al. (1960) reported the metabolism of radiosilver

in a patient with malignant carcinoid that agreed reasonably well

with the carrier-free silver rat studies of Scott and Hamilton

(1950). The radiosilver was incubated with the patient's own blood

and was first associated most with the erythrocytes and the globu-

lin fraction of the plasma (77 percent in the globulin, 15 percent

in the albumin, and 8 percent in the fibrinogen fractions). Upon

injection (i.v.) into the patient (with 0.002 mg carrier Ag/kg),

the 43 pCi radiosilver was removed rapidly from the blood, presum-

ably by the liver with biologic half-life of 48 days. At seven

minutes after injection, only 30 percent of the injected dose

remained in the blood; at two hours, 10 percent remained; and at 1

to 20 days, 2 percent. Urinary excretion was 5 percent of fecal

excretion. Excretion was much slower than in the rat studies.

Only 0.5 to 3 percent of the original dose was eliminated in each of

seven 24-hour periods in the first 21 days post-administration.

Urinary excretion in these 24-hour periods ranged from 0.03 to 0.29

percent.

C-43

---

The patient lived 195 days after the injection. Analysis of

the organs post-mortem showed the highest concentrations (counts

per minute per gram) in: liver, 70.0; skin, 37.7*; kidney (left),

10.0; brain, 9.2; and kidney (right), 7.5. From 4.0 to 5.6 cpm/g

was found in an abdominal lymph node, an adrenal gland, the primary

carcinoid in the ileum, a testis, the aorta, and the pancreas; and

2.2 to 3.8 cpm/g was found in the urinary bladder, prostate, heart,

stomach, rib, and ileum. Smaller concentrations were found in the

carcinoid in the liver (metastatic), a lung, muscle, and the spleen

(Polachek, et al. 1960).

Intramuscular injections of dextrin-protected radiosilver

colloid left much material at the injection site, but an i.v. dose

in albino rats (1 ml contained 1.72 x 10

6

cpm) was mainly found in

the reticuloendothelial system. The bone content was primarily-in

the marrow. The continued presence of activity in the blood sug-

gested that tissue-deposited silver was being translocated. A

gelatin-protected silver colloid injected i.v. into albino mice was

also deposited in highest concentrations in the reticulondothelial

system; 22 hours after i.p. injection of the gelatin-protected sil-

ver colloid into five albino mice, 36.5 percent of the activity was

in the gastrointestinal tract and contents; 16.5 percent in the

liver; 10.2 percent, in muscle; 3.5 percent, in bone; and 0.4 per-

cent, in the skin (except the head) (Gammill, et al. 1950).

Table 8 adapted from Smith and Carson (1977) reviews some

other animal data on early distribution of injected silver com-

pounds.

*Because of its relative weight, the skin had the highest accumula-

tion of silver.

C-44

---

Organism?

Organ

White mice Blood

Liver

Spleen

Stomach

Thyroid

Bone

Form of Ag

10 min.

110A

125-1251i

19.7%

65.6%

0.35%

0.51%

0

0.42%

Total

8T.VC

White mice BlandLiver

?

110A

g

82-nr

Spleen

Stomach

0?

Thyroid

to.a..i

?

?

acne

Total

TABLE 8

Silver Distribution in Animal Tissues

Distribution at

30 min. 1 hr.

?

3 hr.

?

6 hr.?

24 hr. 2 days 7 days Dosage?

Remarks? Reference

?

13.5%?

15.2%?

0

?

0

?

0 0.2 ml. iv.?

Ag alsa found in?

Angliilexi, 1969

?

48.3%?

40.7%?

44.311

?

30.9% 20. 1 10.11% of 50-60

?

kings, kidneys, small

?

0.10%?

0.60%?

0?

0? 0 ug/ml

in?

intestine, intestine,

?

0.92%?

1.25%?

0?

0?

0 tail vein?

bladder, muscle,

?

0.02%?

0?

0?

0? 0?

testesm, and train.

?

0.31%?

0.51%?

0.93%

?

0.01%?

0

6).Ini

5B7171 45.

-2-Ci

Ar.r.% —

r5%

,

-WIT%

Results indicate Ag Anghiksi, 1969

is released in an in-

cm/tip

form and not

as

Ag

r

Radiosilver

is slowly excreted

through bile and

urine.

Rats?

Lungs?

110AgN

2 hr.

Anghileri, 1969

HeartKidneys

?

?

in

at

0.05

pH 5.0

M?

-?FoundFound

Pancreas

?

acetate

Small

?

buffer

?

Found

intestine

Large?

Found

inbmtine

Bladder

?

Found

Muscles

?

Found

Testes

?

Found

Brain

?

Found

Rats

?

Blood

?

ApNO and

?

0.01+pmciles Ag had little effect VanCampen, 1966

Heart

?

''Cu(E0,),

?

Cu in 0.4 on uptake of Cu

Kidneys

?

injected filth?

ml distil.

?

except that a signif1-

Liver

?

in vivo

?

ii3O with?

candy greater propx-

Spleen

?

131 seg-

?

1.5, 3.0,?

tion of Cu was de-

ments of the

?

and 6.0

?

posited in the liver

G.L tract.

?

aides

?

and significantly less

Ai

des

retained by the blood

in Ag-treated rats.

0.82%

1.12%

0.56%

0.2 al.%io

58.7%

63.6%

26.1%

of 50-60

0.34%

0.18%

2.09%

Wail in

0.73%

0.57%

0.41%

tail vein

-

--

0.21%

0.14%

0.45%

60 TO

63:111.

2nri-

---

Deposition of carrier-free radiosilver in rats was similar

after i.m. and i.v. injections. The most interesting information

from the studies of Scott and Hamilton (1950) was the distinct dif-

ference in organ accumulation between carrier-free doses and doses

containing stable silver compound added as carrier. Table 9 shows

the difference in distribution six days after i.m. injections when

three rats per group were given carrier-free silver or radiosilver

with 0.1 mg stable silver (0.4 mg/kg) or with 1.0 mg stable silver

(4.0 mg/kg).

Obviously, the liver had difficulty maintaining its efficient

removal of silver at a dose of 0.1 mg/rat, but the dose of 1.0

mg/rat definitely showed the limitation of its capacity so that the

rest of the reticuloendothelial system had to handle much more

silver. At the highest dose compared with the carrier-free dose,

the liver had accumulated 94 times as much of the absorbed dose of

silver; the spleen, 269 times as much; and the skin, 31 times as

much. Other organs, including the kidney, had about 10 times as

much silver. Scott and Hamilton presumed that a dose of 5 mg silver

per kg i.m. would be required to give a tissue distribution similar

to that seen in classical argyria.

West, et al. (1949, 1950), had shown that

111Ag nitrate when

injected i.m. or i.v.

?

"...is taken up by blood leukocytes and

C-46

---

TABLE 9

Distribution of Silver in the Rat at Day 6 Following

Intramuscular Injections of Different Doses of

Silver (percent of dose per organ)*

Dose

Carrier-Free

0.1 mg

1.0 mg

Percent of Dose

92.1

63.7

53.5

Absorbed

Absorbed

Heart and lungs

0.06

0.13

0.59

Spleen

0.01

0.13

2.69

Blood

0.50

0.95

3.03

Liver

0.36

2.24

33.73

Kidney.

0.07

0.92

0.63

G.I.?

tract

1.12

4.22

8.21

Muscle

0.27

0.56

2.39

Bone

0.18

0.35

2.20

Skin

0.24

0.67

7.39

Urine

0.64

0.88

1.82

Feces

96.56

88.95

37.33

Unabsorbed

7.9

36.3

46.5

*Source: Scott and Hamilton, 1950.

C-47

---

carried into inflammatory body areas."* Presumably, the Ag-protein

complexes formed were phagocytized. Since insoluble silver com-

pounds would be less corrosive and also phagocytized, West and

Goldie (1956), injected normal and tumor-bearing mice with 111

Ag20

to examine the distribution of the radioactivity by autoradio-

graphs. In normal Swiss albino mice given s.c. injections of 0.1

or 0.2 mCi

111

Ag

2 0,

the activity 24 hours after the injection re-

mained mostly at the injection site with a large fraction in the

liver and minor amounts in the spleen, stomach, colon, kidney, and

lung. In normal mice given the injections i.p., most of the activ-

ity was in the liver; some remained at the injection site, but

absorption was much higher than by s.c. injection. Thus, nigher

activity was seen in each of the organs than with s.c. injections.

However, mice with tumors -(Sarcoma 180, Sarcoma McGhee, Carcinoma

C3H/BA, and Carcinoma E0771) showed by far the major activity in

the tumors and intracavity exudates when injected with radiosilver

near the tumor site (s.c. into the tumor periphery, into the

pleural cavity with malignant growth, or into the peritoneal cavity

bearing malignant growth). West and Goldie (1956) explained the

preferential silver absorption by tumors as follows: a s.c. injec-

tion in normal mice remained largely at the injection site, presum-

*West, et al. (1950) found that up to 10 percent of intradermal in-

jections of labeled silver nitrate

(108,110

Ag) remained at the in-

jection site after 72 hours. When Staphylococcus aureus was in-

jected simultaneously in the same leg five times as much silver

was found at the injection site after 72 hours. But if injected

in

different legs, the activity was preferentially found at the

site of bacterial injection.

C-48

---

ably clogging the lymphatics. When adjacent tumors were present,

they apparently absorbed the 111_,2

A

3

0 into macrophages and inter-

space

s

of malignant tissue.

In argyric rats given 0.5 percent silver nitrate in their

drinking water for nine months, silver was especially found in

lysosomes of the liver's Kupffer cells, at the basal membrane of

the capillaries, and the connective tissue cells of the pancreas.

In the parenchymatous cells, Putzke (1967) found silver only as a

lipoid-silver complex or in lipofuchsin-like lysosomes and in

residual bodies. The lysosomes were thought to be responsible for

intracellular transport and the extrusion of silver. In the liver,

there was increased activity of cytochrome oxidase, but marked de-

crease in the activity of succinate dehydrogenase.

Ham and Tange (1972) cited numerous studies wherein silver

nitrate was administered in the drinking water of rats to study

glomerular basement membrane formation. These authors gave drink-

ing water containing 2,500 mg/1 AgNO3

for 12 weeks to albino and

hooded female rats, killing pairs of animals at 1 to 12 weeks to

study the tissues by light and electron microscopy. Other pairs of

animals were killed at 1 to 10 months after silver intake. Four of

each strain were also killed for study 16 months after the cessa-

tion of silver intake. As shown in Table 10 the silver content in

the liver was similar in both strains, but varied by strain and in-

dividuals of the same strain in the kidneys. Abnormalities in

glomerular epithelial and endothelial cells were not progressive or

consistent. Bloom, et al. (1959) cited by Ham and Tange (1972) in

C-49

---

TABLE 10

Silver in Formalin-Fixed Rat Tissues After Drinking

Silver-Containing Water, mg/kg* **

01

a

LT,

Hooded Rats

Albino Rats

Liver

Kidney

Liver

Kidney

3 Months/ intake of

silver at 2,500

mg/1 in drink-

ing water

10 Months after

removal of silver

from drinking water

16 Months after

removal of silver

from drinking water

6.8,

?

7.0

1.4,?

2.8

0.8-1.4

6.1,?

9.8

3.7,?

4.3

2.7-4.1

6.3,

?

7.0

2.2,?

2.5

0.7-1.6

3.7,?

7.1

1.8,

?

3.4

3.0-6.0

* Source: Ham and Tange,

1972.

**Determined by potentiometric titration.

---

observing the phenomenon of increased formation of basement mem-

brane thought the increase might be greater than normal thickening

due to aging.

Moffat and Creasey (1972) fed 10 adult rats and 3 adult rab-

bits drinking water containing 1,500 mg/1 AgNO

3

for 4 to 20 weeks

to study the permeability of medullary vessels of the kidney to

protein. Only the rat kidney showed heavy silver deposits in the

glomeruli and outer medulla basement membranes. Both species had

heavy deposits in the inner medulla, but the distribution differed

markedly. In the rat, most of the silver was in the basement mem-

brane of the vessels and loops of Henle, but the heaviest deposits

were around the descending vasa recta. The main deposits in the

rabbits were also in the vessels and loops of Henle, but the dis-

tribution in each vessel or loop was asymmetrical. Most of the

silver was deposited on the side adjacent to the collecting duct.

In the silver-dosed rats, the occurrence of degenerating kidney

cells was more common than in normal rats.

Creasey and Moffat (1973) also cited several studies in which

silver nitrate had been administered in drinking water to experi-

mental animals to study the basement membranes of some (brain, eye,

and renal glomeruli) of the many kinds of tissues in which silver

accumulates. Silver is carried in the blood as a silver-protein.

complex, and its deposition in tissues appears to indicate vascular

permeability to protein. Extravasation of protein in the kidneys

occurs in immature rats (younger than three months) much less than

in adults. This was shown by the slower rate of appearance (12 to

14 weeks versus 5 weeks) and finer particulate size ( ct30 nm versus

C-51

---

30 to 90 nm) of silver granules deposited in the kidneys of imma-

ture rats given 1,500 mg/1 AgNO3

solution for 4 to 15 weeks after

weaning, as compared with adults on the same regimen. The increas-

ing amount of silver deposited in the rat kidney glomeruli with age

has also been attributed to increasing glomerular filtration rate.

Silver granules were detected by electron microscopy in the

glomerular basement membrane of random-bred adult mice after 12

days of ingesting drinking water containing 6 mM AgNO3

(648 mg/1

Ag). After 14 weeks of silver ingestion, larger aggregates were

observed in the basement membrane and mesangium. Within 21 weeks

after cessation of silver ingestion, the silver deposits did not

change significantly (Day, et al. 1976). Some of the mice were

used in a study of immune complex glomerular disease induced by

i.p. injections of bovine serum albumin. The silver-labeled base-

ment membrane helped determine that the immune deposits were on the

intracapillary aspect of the basement membrane (Hunt, et al.

1976).

Metabolism

Silver is transported in the protein fractions of the plasma,

especially the globulins. The reticuloendothelial system, espe-

cially the liver, handles most of the removal of absorbed silver

from the body at moderate doses (0.4 mg/kg in rats, according to

Scott and Hamilton, 1950). At

higher

doses, deposits are markedly

increased in the skin. Inhaled silver particles that are not re-

moved from the lungs by the mucociliary reflex and coughing are

probably phagocytized and ultimately removed to the liver, from

C-52

---

which they are eventually excreted via the bile. Formation of sil-

ver selenide deposits in the liver may be another method of detox-

ifying silver (the interactions of silver and selenium are dis-

cussed under Synergism and/or Antagonism). Many studies have

focused on elucidating the chemical forms of the silver deposits in

the skin. The most probable forms are metallic silver, silver sul-

fide, or silver complexes with the sulhydryl amino acids in pro-

teins. Since the deposits are so inert, they cannot be removed by

common heavy metal detoxification procedures. These deposits

appear to be another method of detoxification by the organism. In

the kidney, complexation with metallothionein may be another detox-

ification pathway.

Transport of silver in the blood is largely in the globulin

fraction. None of the silver content of blood is dialyzable "to

any extent" through cellophane (Scott and Hamilton, 1948). In

vitro, the distribution of carrier-free

105Ag

after three days in

heparinized rat blood containing an equal volume of isotonic saline

was: hemoglobin, 8.4 percent; ghosts of the cells, 11.6 percent;

globulin, 64 percent; albumin, 16 percent; and the protein-free

fraction, 0.001 percent. In vivo, the distribution of total amount

of radiosilver activity in rat blood five minutes after i.v. injec-

tion was erythrocytes, 10.2 percent; globulin, 57 percent; albumin,

32 percent; and the protein-free fraction, 0.7 percent; the liver

already contained 86 percent of the injected dose by five minutes

(Scott and Hamilton, 1950).

Lifshits (1965) reported the distribution of endogenous silver

in the blood of 16 healthy humans (in mg/1 whole blood). In the

C-53

---

plasma, the fibrinogen fraction contained 0.0018 mg/1; the globu-

lins, 0.0064 mg/1; the albumins, 0.0024 mg/1; and minerals, 0.0014

mg/l. In the erythrocytes, the silver distribution was: stroma,

0.0038 mg/1; nonhemoglobin proteins, 0.0009 mg/1; and erythrocyte

minerals, 0.

Silver iodide is readily broken down by biological tissues.

Anghileri (1968) injected 0.2 ml of

Ag1311

(0.23 mg AgI/ml and 10

pCi

1311/ml)

into the tail veins of young albino mice (15 to 20 g).

In a similar experiment, the silver portion of the molecule was

labeled

?

(Ag).110

Less radioactivity was observed in the liver with

110AgI

than with Ag1311

(53 percent versus 70 percent of the

11

in-

jected dose after 10 minutes), but the

110Ag

radioactivity remained

longer in the liver (21 percent versus 4.1 percent at 24 hours).

The concentration of radioactivity was much higher in the stomach

and thyroid with

1311 than with

110Ag

in the injected silver iodide

during the first 24 hours.

Camner, et al. (1974) reported that silver-coated 5 pm

Teflop

particles were phagocytized in vitro by rabbit alveolar

macrophages in the presence of serum more slowly than were similar

particles coated with aluminum or chromium and at about the same

rate as were particles coated with manganese or uranium. When

serum was not added, there was less difference in phagocytization

rates. The former case is more comparable with the in vivo situa-

tion. (For silver, the average number of particles phagocytized

per macrophage in the presence of serum after 1.5 hours was 0.58;

C-54

---

and for alumir.

1,

0.72. Without serum, the numbers were 0.38 and

0.40, respectively.) There were fewer than 4 percent nonviable

macrophages after the 1.5-hour exposure of a monolayer of macro-

phages from disease-free rabbits to the particle suspension in 75

percent Parker 199 solution and 25 percent autologous rabbit serum

or in 100 percent Parker 199 solution.

After daily applications of 1 percent silver sulfadiazine

cream to the abraded skin of albino rabbits for 100 days at dosages

of 5.0, 10.0, or 15.0 g/kg/day, the kidney tissues were treated

with various solvents* in an effort to determine the chemical form

of the silver deposit. Sulfadiazine was not detected in chloroform

extracts of acidified tissue homogenates.** Since only the

strongly oxidizing solvent 16M nitric acid dissolved any of the

kidney tissue silver deposits (the range of silver concentrations

in four rabbit kidneys by atomic absorption spectrometry was 172.3

to 247.0 mg/kg), Grabowski and Haney (1972) concluded that the form

of silver was as a silver tissue complex whose dissociation under

normal conditions would be minimal, and whose only physiological

threat would be mechanical interference to kidney function. No

structural damage or impairment had been noted in the kidneys, how-

ever.

* 16M HNO3

, 30 percent NH4OH,

50 percent CH3CO2H,

9 percent

H 2NCSNH 2

, 37.5 percent HC1.

**The sulfadiazine probably remained in the acid solution as a

salt: A-

+NH3C6H5SO2NHC4N2H3

.

C-55

---

Pariser (1978), using the differential solubility methods*

of Buckley, et al. (1965), found that only cyanide solutions re-

moved the silver from tissue sections of argyric patients (ages 83,

58, and "elderly"). This suggested that the chemical form of

silver was as silver sulfide or some other highly insoluble complex

rather than metallic silver.

Chromatographically purified metallothionein from normal rat

liver contained significant concentrations (by neutron activation

analysis) of Cd, Zn, Cu, Hg, and Ag. Experiments with 110m

Ag+

showed further incorporation into metallothionein (Sabbioni and

Girardi, 1977). Possibly this is the mechanism whereby the kidneys

excrete bound silver.

Excretion

Regardless of route and chemical form administered, fecal

excretion of silver always predominates over urinary excretion.

Most absorbed silver is excreted into the intestines by the liver

via the bile.

Scott and Hamilton (1950) showed that the liver is the chief

organ responsible for elimination of absorbed silver. The silver

content in the liver, feces, and gastrointestinal tract contents

was reduced when bile duct ligation or light chloroform anesthesia

(which produces liver damage) in rats was performed prior to injec-

tion of carrier-free radiosilver. Ordinarily, after i.m. injection

*Tissues were extracted with thiosulfate fixing bath (dissolves

silver mercaptides, oxides, chlorides, bromides, iodides, car-

bonates, and phosphates); ferricyanide-bromide bleach followed

by

thiosulfate fixing bath (dissolves metallic silver); and 5 percent

sodium cyanide (which dissolves most insoluble silver salts such

as silver sulfide).

C-56

---

of 1 pCi radiosilver (0.1 pg), 60.9 percent of that absorbed was

excreted in the feces on the first day, and 21.4 percent was al-

ready in the gastrointestinal (G.I.) tract. After bile duct liga-

tion, on day 2, 57.6 percent of the activity still remained in the

liver, 5:06 percent was in the G.I. tract, and only 6.85 percent

was in the feces. After light chloroform anesthesia for three

hours, the rats excreted silver at 0.0001 the normal rate.

Urinary excretion of silver is generally very low. At four

days after an intravenous (i.v.) dose of radiosilver, rats had ex-

creted 94.06 percent of the dose in the feces and 0.34 percent in

the urine and at 16 days, 97.8 percent and 1.8 percent, respec-

tively (Scott and Hamilton, 1950). Administration of Ca EDTA, a

common metal chelating agent, reportedly increased urinary excre-

tion of silver. Ligating the bile duct in laboratory animals in-

creased renal excretion while reducing fecal excretion by a factor

of 10, thereby further demonstrating the biliary nature of silver

excretion (Furchner, et al. 1968). Radiosilver (

110

Ag) iodide was

removed from the blood two hours after i.v. administration and was

slowly excreted through the bile and urine in a nonionic form

(Anghileri, 1971). The ratio of urinary-fecal excretion is 0.001

to 0.258 (Furchner, et al. 1968; Kalistratova, et al. 1966; Anghi-

leri, 1969).

Dequidt, et al. (1974) found significant silver excretion in

the urine after several i.p. injections of different forms of sil-

ver medicinals. Wistar rats given 12.6 mg/kg silver i.p. as the

nitrate daily for five weeks (apparently a 4-day work week) elimi-

nated 10 to 20 pg/rat/day in the urine. At 5 mg/kg/day silver as

C-57

---

silver nitrate for 24 injections within six weeks the urinary

silver excretion was 3 to 15 pg/rat/day (average 4 pg). When

injections of 29.6 mg/kg colloidal silver were given to rats 11

times within three weeks, the urinary excretion was 8 to 24 pg/

rat/day (average 12.6 pg). Colloidal silver i.p. injections at 5

mg/kg/day for 24 injections within six weeks gave urine containing

2 to 10 pg/rat/day. Silver proteinate i.p. injections (16 within 4

weeks) at 5 mg/kg gave urinary silver contents of 3 to 15 pg/rat/

day.

In rats, silver is eliminated from the lungs in two or three

phases. The fastest phase (0.3 to 1.7 days) removes most of the

inhaled dose by mucociliary clearance. A second phase and third

phase remove absorbed silver, mostly via the liver, with half-lives

of about 8 to 15 and 40 to 50 days, respectively.

As of 1964,

110mAg had been detected 583 times in 186 dif-

ferent individuals in the nuclear industry. Sill, et al. (1964)

described the inhalation exposure of 50 people to activation prod-

uct 110mAg

when an experimental loop containing silver-soldered

thermocouples in the Engineering Test Reactor was opened. Re-

exposure occurred during cleanup procedures, complicating data

interpretation; but the calculated effective half-life was about

eight days before recontamination. The source of the

110m

Ag and

the time of exposure was not the same for all subjects. The indi-

vidual with the highest body burden of 0.93 pCi had an elimination

rate with a half-life of 13 days. Two others had effective half-

lives of 17 and 69 days. (The International Commission on Radio-

logical Protection gives 4.9 days for whole-body elimination half-

life.)

C-58

---

In most cases, maximum activity occurred in the nose, mouth,

chest, and lower edge of the rib cage. In almost all the cases,

110mAg

could not be detected in 1,500-m1 urine samples (Sill, et

al. 1964).

At Harwell, England, a 29-year-old man accidentally inhaled

dust from an experimental hole in a nuclear reactor. The burden of

radionuclides was below the maximum permissible, but the levels of

65

Zn and

110mAg allowed prolonged study of their retention and dis-

tribution (Newton and Holmes, 1966). Whole-body gamma-ray spec-

trometry on the second day after the accident showed 197 nCi 110mAg

(and 330 nCi

65Zn).

By day 6, 90 percent of the zinc still re-

mained, but only 40 percent of the silver seen on day 2 remained.

About 25 percent of the total activity appeared to be confined to

the region of the liver. The

110mAg

appeared to be more closely

confined to the liver than was the

65Zn

on day 16, when individual

measurements were made. For 155 days, after which the silver dis-

tribution studies were abandoned, the liver was the major site of

deposition. The whole-body effective half-life of the 15 percent

retained silver was 43 days (biological half-life 52 days).* Dur-

ing the first 100 days, the content in the liver appeared to

decrease at about the same rate, but there was a longer-lived com-

ponent that may have been an artifact from

137Cs.

There

was

no sil-

ver in the urine during the first 54 days, but it was present in

fecal samples up to about day 300.

*Polachek, et al. (1960) had reported a value of 48 days for liver

clearance. The International Commission on Radiological Protec-

tion in 1959, however, quoted a value of 15 days.

C-59

---

The M.S. theses of Phalen (1966) and Garver (1968) reported

controlled inhalation studies in which rats were exposed, nose

only, to

110mAg-tagged

silver smoke. Clearance from the body was

described in two exponential functions of biological half-lives, 8

days and 20 days, indicating two separate body pools of silver

(Phalen and Morrow, 1973).

The initial rapid clearance from the lung is on the order of

several hours or one or two days (Phalen, 1966; Garver, 1968;

Skolil, et al. 1961; and Newton and Holmes, 1966). In humans, 80

percent was cleared from the lungs with a biological half-life of

one day. The half-life for the remainder in the Skolil, et al.

(1961) report was 15 days (Phalen and Morrow, 1973).

Phalen and Morrow (1973) studied six female beagle dogs who

received single acute inhalation exposures to

110mAg-tagged

silver

aerosol via tracheal tubes (for 7 to 15 minutes while anesthe-

tized). The method of aerosol generation (by wire explosion) in-

sured well-characterized spherical particles, primarily of metal-

lic silver. The activity median aerodynamic diameters were 0.5 p.

Absolute deposition in the lungs was 1 pg/kg (in text; in the

author's abstract the value given is 1 mg/kg).

The solubility rate constants were: in distilled water, 0.1

pg/cm2/day

at 35 to 37°C; and in simulated interstitial fluid, 10

pg/cm2/day.

One could expect 99 percent of the aerosol mass in the

lung to dissolve in two days.

The activity appeared to clear at about 6 to 8 hours. One dog,

exposed for 15 minutes, was sacrificed six hours post exposure.

There was 96.9 percent of the initial deposit still in the lungs,

C-60

---

2.4 percent in the liver, 0.38 percent in the blood, and 0.02 per-

cent in the stomach. The solubility rate constant in the lung was

calculated to be 1 pg/cm

2

/day. Perhaps some dissolved silver re-

mained in the lung as a tissue complex. By three days, half of the

initial amount deposited was gone. Since only 20 percent appeared

in the excreta during the first five days, most of the silver was

not removed by the mucociliary mechanism. Perhaps 90 percent was

carried by the blood to the liver. For three dogs, the major silver

repositories were the liver, lungs, brain, skin, and muscle; one of

the dogs had larger amounts in bile, liver, and bone (Table 11).

Where larger particles are inhaled, elimination may more

resemble that observed after oral dosing, when much of the lung

deposit has been eventually swallowed.

Camner, et al. (1977) found that inhaled 4-pm TefloOpar-

ticles coated with carbon, silver, or beryllium were cleared from

rabbits' lungs (8 to 10 New Zealand rabbits per test) at about the

same rate during the first week, despite differences in their tox-

icity and in the rates of in vitro phagocytosis that had been

reported. Presumably, intact particles of the size and lung burden

used (aerosol inhaled for only 6 to 8 minutes, resulting in 1 to 10

pCi and 10 to 100 pg deposition) were not actively removed from the

lungs by the alveolar macrophages during the first week after inha-

lation. External measurements of clearance could be made because

all of the particles were tagged with 51Cr.

The silver-coating remained 50 percent intact in rabbit serum

(replaced daily) at

37°C for 12 days. But in a flow-through system

C-61

---

rn

TABLE 11

Biological Half-Lives (t

1/2

) in Days for Clearance

in 4 Dogs After Inhalation of Silver Aerosol*

Pooled Data

Lung

t1/2

?

t1/2

ti/2

Liver

?

Body

t

1/2

by analysis

of excreta

t

1/2?

t

1/2?

(1% in urine)

Dogs 1, 3, 4,

?

1.7

?

8.4

?40

? 9.0

? 40? 8.4 - 12.9

and 5

?

(97% of

that

excreted)

*Source: Phalan and Morrow, 1973.

---

with 10 percent horse serum in saline at 37°C for eight days, 26

percent of the particles had lost more than half their coatings.

Kent and McCance (1941) followed the excretion of silver for

three separate 7-day periods in a woman with severe generalized

argyria produced by "washing out her nose for many years with an

organic silver preparation." Her negative balances (Table 12) may

have been due to desquamation of the silver-containing cells from

the alimentary canal lining.

Enders and Moench (1956) reported that argyric albino rats

with varying degrees of heavy silver deposits in the liver and very

weak to heavy deposits in the kidney after consumption of a silver

medicinal (Targesi for three months, showed progressively less

silver in these organs after the silver feeding had been stopped.

At three months postexposure, the liver deposits in 10 rats were

only very weak or entirely absent; and there were no deposits in

the kidneys and duodenum. After six months on a normal diet, four

of the nine rats showed very weak silver deposits in liver, kidney,

and/or duodenum.

Buckley and Terhaar (1973) reported that the skin is an excre-

tory organ in generalized argyria with gradual translocation of

silver from the general body pool through the dermis and finally

into the epidermis as soluble silver. One worker with generalized

argyria was studied. Silver appeared to be released from melanin-

silver complexes as a soluble ionic form near the surface of the

epidermis.

In rats, mice, and rabbits, 99 percent of a one-time oral dose

of silver is eliminated within 30 days. Dogs, which absorb 10

C-63

---

■

TABLE 12

Silver Balance in a Female With

Severe Generalized Argyria*

Silver, mg/week

Week 1

Week 2

Week 3

Food

0.05

0

0.7

Feces

1.3

1.5

2.3

Urine

0

0

0

Balance

-1.25

-1.5

-1.6

*Source: Kent and McCance, 1941

C-64

---

percent of the dose, require more than 28 days. Snyder, et al.

(1975) for the International Commission on Radiological Protection

reviewed

the literature pertaining to the silver balance for refer-

ence man and concluded that his intake in food and fluids is 70

pg/day and his losses include 9 pg/day in urine, 60 pg/day in

feces, 0.4 pg/day in sweat, and 0.6 pg/day in hair.

Tipton and Stewart (1970) reported that the range of silver

found in the ash of food was 0.5 to 75 mg/kg; of feces, 1 to 115

mg/kg; and urine, 0.0 to 15 mg/kg (analysis by spectrographic pro-

cedures).

Kehoe, et al. (1940) found only 0.06 mg/silver/day eliminated

in the feces, which was less than the 0.088 mg/day dietary intake

of silver. Although silver was detected in the blood of Americans,

Frenchmen, Mexicans, and Germans, it was not detected in their

urine. Almost all silver is excreted in the feces of mammals with

only traces in the urine (Gammill, et al. 1950; Scott and Hamilton,

1950). However, silver may be detected in urine in cases of silver

poisoning (Sunderman, 1973). Silver has also been detected in

nasal and vaginal secretions (Barsegyants, 1967).

Analyses for silver were made on diets and excreta of a hus-

band (Subject B) and wife (Subject A) for 30 days. Subject B had a

mean intake of 0.035 mg silver per day and Subject A, 0.04 mg silver

per day, respectively. Subject A drank five cups of coffee (not

analyzed for silver content) per day, had a fecal/urinary silver

excretion ratio of 3, and a positive average silver daily balance

of 0.007 mg/day (2.6 mg/yr). Subject B drank three glasses of milk

per day (analyzed for silver content), had a fecal/urinary excre-

C-65

---

tion ratio of 8, and a negative average daily silver balance of

0.054 mg after 30 days (Tipton, et al. 1966).*

Average human intake from the diet is estimated at up to 0.088

mg/day (Kehoe, et al. 1940). At that rate, if 100 percent of the

silver ingested is retained in the body, approximately 31 years

would be required to accumulate 1 g of silver. Based on the data of

Tipton and Cook (1963), the average silver content in wet tissue of

Americans is about 0.05 ppm. The body of a 150-lb human, whose tis-

sue content was 0.05 ppm, would contain only 32 mg silver or 3.2

per cent of a 21-year ingestion total. It would appear that very

little of the silver ingested from nontherapeutic sources is actu-

ally retained in the body.

Excretion of radiosilver

( 11°AgNO

3

) was faster, and a larger

percentage of it was excreted in test animals when it was admin-

istered orally than when it was injected either i.p. or i.v. More

than 90 percent of the carrier-free silver administered by any of

these routes was excreted in the feces with at least 90 percent of

the orally ingested silver not being absorbed.

In beagle dogs (average age 5.5 years, 12 to 16 kg) given oral

doses of 6 uCi

11110Ag

as the nitrate, about 10 percent of the dose

was absorbed. About 70 percent of the absorbed dose had a bio-

logical half-life of about one month. Dogs retained 1 percent of

the dose for at least four weeks (Furchner, et al. 1968).

*Subject A retained 16 percent of the dietary silver she ingested,

but Subject B excreted 2.5 times more silver than he ingested from

his diet. (Both A and B excreted about the same amounts of silver

in their urine.) Subject B was also in negative balance for cop-

per, barium, and nickel. His medicine intake and occupation were

not mentioned nor was the state of his dental restorations.

C-66

---

Female RF mice (eight weeks old, 2 g), given

?

110.y

a as the

nitrate i.p., i.v. (tail vein or jugular vein), or orally (12 mice

per route) lost half the dose much faster than did the rats of Scott

and Hamilton (1950). The rats required 30 days to eliminate 99

percent of the dose, whereas the mice required only 18 days.

Almost the entire oral dose (given by stomach tube) was lost by the

mice with a biological half-life of 0.125 day. The biological

half-life of the remainder was 1.5 days. "The body burden under

conditions of chronic oral ingestion would be only about one-fifth

of the daily dose" (Furchner, et al. 1966a).

The plots of effective retention versus time of oral doses of

110.g

A

in 12 mice, 6 rats, 4 monkeys, and 4 dogs showed that within

the first day or so, the rate of elimination decreased in the

order: rats-->dogs--mice-->monkeys; but at 5 days, the order was

rats-=>mice--3monkeys-.4dogs; and at 15 to 35 days, the order was

mice--->rats-->monkeys-i0ogs. The urinary/fecal ratio on day 1 for

rats and mice was 0.001; for monkeys, 0.02 (Furchner and Drake,

1968).

When a one-time dose of

110mAgI

(1 pCi 110mAg in 0.5 g AgI) was

force-fed to three cottontail rabbits, 99 percent of the dose was

excreted within three days, the elimination half-life being 0.48

day. From 8 to 26 percent of the radiosilver entered the cecum (as

judged in three rabbits prevented from reingesting their cecal pel-

lets) (Jones and Bailey, 1974).

Four rabbits were fed 0.00042 percent silver, in the dry mat-

ter of feed, as silver iodide complexes prepared to simulate cloud-

seeding generator products for 30 days. The concentrations of

C-67

---

silver in the dry matter of feces and cecal contents were similar

(4.2 to 5.2 mg/kg). The silver content of the dry matter of their

livers (0.2 mg/kg) was the same as that in four control rabbits fed

a normal diet (0.00001 percent silver); thus, absorption was not

likely (Jones and Bailey, 1974).

Roy and Bailey (1974) concluded that accumulation of silver in

the rumen of any ruminant species upon chronic intake is not

likely. The presence of chloride ions, protein, bacteria, and

other organic matter in the rumen inhibit the antimicrobial action

of silver ions and insure that most of the ingested silver* passes

from the rumen in an insoluble form.

EFFECTS

Acute, Subacute, and Chronic Toxicity

The toxicity of silver compounds could be classified as moder-

ate, although large doses of silver compounds may have serious

effects (Table 13). For example, ingestion of 10 g silver nitrate

is usually fatal. In humans taking large doses of silver nitrate

orally, the patient suffers violent abdominal pain, abdominal

rigidity, vomiting, and convulsions and appears to be in severe

shock. Patients dying after i.v. administration of Collargo0

(silver plus silver oxide) showed necrosis and hemorrhages in the

bone marrow, liver, and kidney (Hill and Pillsbury, 1939). In the

body, silver may be precipitated by protein or chloride ion. Table

salt (sodium chloride) is an antidote for silver nitrate poisoning.

*Silver iodide or silver nitrate at levels simulating 0.0001 per-

cent and 0.01 percent, respectively, in the dry feed were inserted

with small amount of feed in nylon bags into fistulas in the ru-

mens of goats.

C-68

---

Oral

2-30 g AgNO3.

A few hr.

to a few

days

Oral metallic

?

50-260 g

Ag

TABLE 13

Acute Toxic Effects of Silver on Humans*

How

?

Survival

Administered

?

Dosage

?

Time

?

Observed Effects

?

Remarks

i.v. Collargoin 36 cc of 12%

soln.

i.v. Collargo0 32 cc of 5%

soln.

i.v. Collargo0 To fill renal

pelvis for

X-ray study

i.v. CollargoCD 10 cc of 2%

soln.

Intravaginally 2 cc unknown

concn. of

AgNO3

Oral?

8 g AgNO3

in

soln.

3-14 days

3-14 days

5 min.

Purpura hemorrhagica on the

4th day. Death. Ag chiefly

in the reticuloendothelial

system.

Extensive necrosis and hemor-

rhage of bone marrow, liver,

and kidney.

Death. Severe hemorrhagic

diathesis with parenchyma-

tous hemorrhages in the stom-

ach, intestines, and body

cavities.

Cyanosis, coma; death due to

pulmonary edema.

Death.

Vomitus contained AgCl.

No Ag found in

lungs.

Abortion attempt.

Death possibly not

due to AgNO3.

Patient recovered.

10 g is usually

fatal, but 30 g has

been survived.

Usually death at dosages

10 g.

Gastric fullness, anorexia,

gastric pain, and/or diarrhea.

*Source: Hill and Pillsbury, 1939.

---

II

There is little likelihood of systemic effects in people recovering

from toxic doses, but silver may cause degenerative liver changes

(Dreisbach, 1963).

The most common noticeable effects of chronic and, less fre-

quently, subacute human exposure to silver or silver compounds are

generalized argyria, localized argyria, and argyrosis (argyria of

the eye unless stated otherwise). The two most important causes of

argyria are medicinal application of silver compounds and occupa-

tional exposure. Numerous case histories from Hill and Pillsbury

(1939) are summarized in Table 14. Generalized argyria is a slate

gray pigmentation of the skin, hair, and internal organs caused by

deposition of silver in the tissues. The degree of pigmentation is

highest in areas of the skin most exposed to light, but the concen-

tration of silver in the skin from various parts of the body is the

same. Silver also accumulates in the blood vessels and connective

tissue. Additional manifestations of generalized argyria include:

silver coloration of fingernails and conjunctiva and blue halo

around the cornea. In localized argyria, only limited areas are

pigmented.

Every silver compound in common chemical use has caused gen-

eralized argyria. Of 239 recorded cases of generalized therapeutic

argyria analyzed by Hill and Pillsbury (1939), 118 were caused by

silver nitrate and 28 by Argyro0(mild silver protein), the second

most frequent causative agent. Only 19 were caused by i.v. injec-

tion of silver arsphenamine. Of 178 cases, in which the route was

C-70

---

Ag impregnation of?

ACGIH, 1971

vascular elastic mem-

branes.

5-fokl

the

recom mended 3

TLV, 0.05

mg/le

•

would lead to

accumulation of

L2 g Ag.

Primarily in

?

Attracted via

Lung and G.L?

feces; only

tract? traces in

urine.

Very slight,

over 3 week-

long perk/ob.

11 were affected In

upper respiratory

passages. 9 in con-

junctiva a oomea.

GS. tract a by

dust inhalation.

ACGIH, 1971

ACGIH, 1971

ACGIH, 1971

ACGIB, 1971

Browning, 1961

Browning, 1961

TABLE 14

Argyria

Time Until

Length of Appearance Ag Intake

?

Ag

Observed Effect

Ag Compourd Exposure Conditions Exposure of Argyria a Total Dam

?

Excretion

?

Remarks

?

Reference

fl

Generalized argyria

Generalized argyria

Ag particles?

Sliver polishers?

Long periods

Ag particles?

Penetration of fine

particles

Ag sans?

Ingestion a inhalation

of Ag salts

1-2 mg Ag/m3

In air

during spraying opera-

tions in manufacturing

Ag varnish and in silver-

ing

radio-tech. parts

Breathe 10 m

3

air/

?

20

years

day retention Of

50i of Ag (assumed)

Medication a

industrial

exposure

Increased densi-

tries In lung

X-rays

Localized

argyria

Generalized

argyria

Argyrosis

Generalized

argy- Ag in air

ria, possibility of

Argyria -

in

recognizable

health disturbances

Pulmonary argyria

Possible cause of

kid-

ney

lesions with con-

sequent dangers of

arteriosclerosis and

lung damage but not

fitoais.

Often have

bronchitis

and emphysema, but

no cause-effect rela-

tionship has been

established.

Browning, 1961

Gafafer, 1969

---

TABLE 14 (Continued)

Time Until

Length of Appearance Ag Intake

?

Ag

Observed Effect Ag

Compound?

Exposure Conditions Exposure

?

of Argyria a Total Dose

?

Excretion

?

Remarks

?

Reference

Lung pigmentation

Generalized

argyria

Generalized

argyria

Generalized

argyria

Generalized

argyria

Generalized

argyria

Generalized

argyria

Incalized argyria

Argyrosis

Industrial

argyrosis

Lncatived argyria

of gums

Mottled pig men-

teat

Ag

and

Fe203

AgNO3

ProtargoiA)

AgN 03, tick

Collarga0

Ag arsvinn-

amine

Dental

alloy

AgC:C H

Waked as a silver

finisher

Administered orally

to treat epilepsy and

G.I. symptoms

300-g saint.

into urethra daily

Local application 6x

sere throat and ton-

gue ulcers

Administered orally

to treat pulmonary

tuberculosis

Lv.

During preparation for

a dental crown

Due primarily to Fe,

but Ag present

201 cases from

1700 to 1939

17

cases

from

1700 to 1939

57 cases from

1700 to 1939

12 cases from

1700 to 1939

Johnstone and

Miller,

1960

Hill and

Pincilnry,

1939

Hill and Pillsbury,

1939

Hilt and Pillsbury,

1939

Hill and Pillsbury,

1939

Hill and Pillsbury,

1939

Hill and

PlutnrY,

1939

Hill and Pillsbury,

1939

Hill and Finsbury,

1939

Hill and Pillsbury,

1939

Burton, 1970

Weeks to 20 Lg., 2 years 9-1,000 g

years?

after taking

600 g for

L2 year

2 days

?

3 days

0.5-20 years E.g., 1 year

(when used for

3 years)

E.G., 5

years

1

year?

50-530 g

(260 g Ag)

2-10 years 16

maths to

0.91-7.6 g

9 years

ExPladon

Caused blue pig men-

Orentreich and Pearlstein,

ration? 1969

---

other than i.v., 89 were caused by oral intake of silver, chiefly