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Silver cyanide (CASRN 506-64-9)

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Silver cyanide; CASRN 506-64-9

Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data, as outlined in the IRIS assessment development process. Sections I (Health Hazard Assessments for Noncarcinogenic Effects) and II (Carcinogenicity Assessment for Lifetime Exposure) present the conclusions that were reached during the assessment development process. Supporting information and explanations of the methods used to derive the values given in IRIS are provided in the guidance documents located on the IRIS website.

STATUS OF DATA FOR Silver cyanide

File First On-Line 01/31/1987

Category (section)
Status
Last Revised
Oral RfD Assessment (I.A.) on-line 02/01/1996*
Inhalation RfC Assessment (I.B.) no data
Carcinogenicity Assessment (II.) no data

*A comprehensive review of toxicological studies was completed (2004) - please see section I.A.6 for more information.

_I.  Chronic Health Hazard Assessments for Noncarcinogenic Effects

_I.A. Reference Dose for Chronic Oral Exposure (RfD)

Substance Name — Silver cyanide
CASRN — 506-64-9
Last Revised — 02/01/1996

The oral Reference Dose (RfD) is based on the assumption that thresholds exist for certain toxic effects such as cellular necrosis. It is expressed in units of mg/kg-day. In general, the RfD is an estimate (with uncertainty spanning perhaps an order of magnitude) of a daily exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime. Please refer to the Background Document for an elaboration of these concepts. RfDs can also be derived for the noncarcinogenic health effects of substances that are also carcinogens. Therefore, it is essential to refer to other sources of information concerning the carcinogenicity of this substance. If the U.S. EPA has evaluated this substance for potential human carcinogenicity, a summary of that evaluation will be contained in Section II of this file.

__I.A.1. Oral RfD Summary

Critical Effect
Experimental Doses*
UF
MF
RfD

Rat Chronic Oral
Study

Howard and Hanzal,
1955

NOAEL: 10.8 mg/kg/day
cyanide converted to
55.7 mg/kg/day of
silver cyanide
100
5
1E-1
mg/kg/day


Weight loss, thyorid
effects and myelin degeneration

Rat Subchronic to
Chronic Oral Bioassay

Philbrick et al., 1979


LOAEL: 30 mg/kg/day
cyanide
(155 mg/kg/day AgCN)

*Conversion Factors and Assumptions — molecular weight conversion factor = 134/26 [MW AgCN = 134; MW CN = 26]

__I.A.2. Principal and Supporting Studies (Oral RfD)

Howard, J.W. and R.F. Hanzal. 1955. Chronic toxicity for rats by food treated with hydrogen cyanide. Agric. Food Chem. 3: 325-329.

Philbrick, D.J., J.B. Hopkins, D.C. Hill, J.C. Alexander and R.G. Thomson. 1979. Effects of prolonged cyanide and thiocyanate feeding in rats. J. Toxicol. Environ. Health. 5: 579-592.

Silver cyanide is not soluble in water or dilute acid (Windholz, 1983). Currently the database does not provide any toxicity information on silver cyanide. It is, therefore, recommended that an RfD of 8 mg/day for a 70 kg person based on cyanide (CN) will provide adequate protection against an adverse health effects. Note that this is a conservative protective assumption in light of silver cyanide's lack of solubility.

In this 2-year dietary study, rats (10/sex/group) were administered food fumigated with hydrogen cyanide. The average daily concentrations were 73 and 183 mg CN/kg diet. From the data reported on food consumption and body weight, daily estimated doses were 4.3 mg and 10.8 mg CN/kg bw. The average food CN concentrations were estimated based on the authors' data for concentration at the beginning and end of each food preparation period and by assuming a first-order rate of loss for the intervening period. There were no treatment-related effects on growth rate, no gross signs of toxicity, and no histopathological lesions.

Studies by Philbrick et al. (1979) showed decreased weight gain and thyroxin levels and myelin degeneration in rats at 30 mg/kg/day CN. Other chronic studies either gave higher effect levels or used the subcutaneous route (Crampton et al., 1979; Lessell, 1971; Herthing et al., 1960). Human data do not provide adequate information from which to derive an RfD because effective dose levels of chronically ingested CN are not documented. Therefore, the study of Howard and Hanzel (1955) provides the highest NOAEL, 10.8 mg/kg/ day for CN, and is chosen for the derivation of an RfD for CN of 1.5 mg/day or 0.02 mg/kg/day.

Cyanide is metabolized extensively in the liver, indicating that the only relevant route of administration for quantitative risk assessment in the derivation of an oral RfD is the oral route of administration.

__I.A.3. Uncertainty and Modifying Factors (Oral RfD)

UF — According to the U.S. EPA (1985), an uncertainty factor of 100 is used to derive the RfD (10 for species extrapolation, 10 for sensitive population).

MF — A modifying factor of 5 is used to account for the apparent tolerance to cyanide when it is ingested with food rather than when it is administered by gavage or by drinking water.

__I.A.4. Additional Studies/Comments (Oral RfD)

Decreased protein efficiency ratio was produced by dietary cyanide treatment of rats during gestation, lactation, and postweaning growth phase in the Tewe and Maner (1981a) experiment; the dose level of cyanide (10.6 mg/kg/day) producing that effect is slightly lower than the currently accepted NOAEL of 10.8 mg/kg/day (U.S. EPA, 1985). Furthermore, Tewe and Maner (1981b) tested sows. Possible effects observed at about 9.45 mg/kg/day were proliferation of glomerular cells of the kidneys and reduced activity of the thyroid glands in the young sows. However, the number of animals in this experiment was very small. A Japanese study (Amo, 1973) indicated that 0.05 mg/kg/day of cyanide obtained from drinking water decreased the fertility rate and survival rate in the F1 generation and produced 100% mortality in the F2 generation in mice. However, these data are not consistent with the body of available literature.

__I.A.5. Confidence in the Oral RfD

Study — Medium
Database — Low
RfD — Low

The confidence in the study is medium because adequate records of food consumption and body weight were maintained, and animals of both sexes were tested at two doses for 2 years. The database is rated low because this chemical has not been tested. The confidence in the RfD is low because it is based on analogy. Chronic/reproductive studies are needed to support a higher level of confidence in the RfD.

__I.A.6. EPA Documentation and Review of the Oral RfD

Source Document — U.S. EPA, 1984

Other EPA Documentation — U.S. EPA, 1985

Agency Work Group Review — 08/05/1985

Verification Date — 08/05/1985

A comprehensive review of toxicological studies published prior to 2004 was conducted. No new health effects data were identified that would be directly useful in the revision of the existing RfD for Silver cyanide and a change in the RfD is not warranted at this time.

__I.A.7. EPA Contacts (Oral RfD)

Please contact the IRIS Hotline for all questions concerning this assessment or IRIS, in general, at (202)566-1676 (phone), (202)566-1749 (FAX) or hotline.iris@epa.gov (internet address).

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_I.B. Reference Concentration for Chronic Inhalation Exposure (RfC)

Substance Name — Silver cyanide
CASRN — 506-64-9

Not available at this time.

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_II.  Carcinogenicity Assessment for Lifetime Exposure

Substance Name — Silver cyanide
CASRN —506-64-9

This substance/agent has not undergone a complete evaluation and determination under US EPA's IRIS program for evidence of human carcinogenic potential.

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_III.  [reserved]
_IV.  [reserved]
_V.  [reserved]


_VI.  Bibliography

Substance Name — Silver cyanide
CASRN — 506-64-9
Last Revised — 01/01/1990

_VI.A. Oral RfD References

Amo, H. 1973. Effects of oral administration of cyanide and heavy metals in long term on breeding and chromosomes analyses of mice. Nagoya shiritsu Diagaku Igakkai Zasshi. 24(1): 48-66.

Crampton, R.F., I.F. Gaunt, R. Harris et al. 1979. Effects of low cobalamin diet and chronic cyanide toxicity. Toxicology. 12: 221-234.

Herthing, G., O. Kraupp, E. Schnetz and S. Weeketich. 1960. Untersuchungen uber die Folgen einer chronischen Verabreichung akut toxischer Dosen von Naturimcyanid an Hunden. Octa Pharmacol. Toxicol. 17: 27-43.

Howard, J.W. and R.F. Hanzal. 1955. Chronic toxicity for rats of food treated with hydrogen cyanide. Agric. Food Chem. 3: 325-329.

Lessell, S. 1971. Experimental cyanide optic neuropathy. Arch. Opthalmol. 86(2): 194-204.

Philbrick, D.J., J.B. Hopkins, D.C. Hill, J.C. Alexander and R.G. Thomson. 1979. Effects of prolonged cyanide and thiocyanate feeding in rats. J. Toxicol. Environ. Health. 5: 579-592.

Tewe, O.O. and J.H. Maner. 1981a. Long-term and carry-over effect of dietary inorganic cyanide (KNC) in the life cycle performance and metabolism of rats. Toxicol. Appl. Pharmacol. 58: 1-7.

Tewe, O.O. and J.H. Maner. 1981b. Performance and pathophysiological changes in pregnant pigs fed cassava diets containing different levels of cyanide. Res. Veter. Sci. 30: 147-151.

U.S. EPA. 1984. Health Effects Assessment for Cyanides. Prepared by the Office of Health and Environmental Assessment, Environmental Criteria Assessment Office, Cincinnati, OH for the Office of Emergency and Remedial Response, Washington, DC.

U.S. EPA. 1985. Drinking Water Criteria Document for Cyanides. Prepared by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment, Cincinnati, OH for the Office of Drinking Water, Washington, DC.

Windholz, M. 1983. The Merck Index. Merck and Company, Inc., Rahway, NJ.

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_VI.B. Inhalation RfC References

None

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_VI.C. Carcinogenicity Assessment References

None

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_VII.  Revision History

Substance Name — Silver cyanide
CASRN — 506-64-9

Date
Section
Description
03/31/1987 I.A.6. Documentation corrected
03/01/1988 I.A.5. Confidence levels revised
01/01/1990 I.A.2. Add Philbrick et al. 1979 citation
01/01/1990 VI. Bibliography on-line
01/01/1992 I.A.7. Primary contact changed
01/01/1992 IV. Regulatory actions updated
02/01/1996 I.A.7. Contact changed
04/01/1997 III., IV., V. Drinking Water Health Advisories, EPA Regulatory Actions, and Supplementary Data were removed from IRIS on or before April 1997. IRIS users were directed to the appropriate EPA Program Offices for this information.
12/03/2002 I.A.6. Screening-Level Literature Review Findings message has been added.
09/29/2004 I.A.6. Screening-Level Literature Review Findings message has been removed and replaced by comprehensive literature review conclusions.

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_VIII.  Synonyms

Substance Name — Silver cyanide
CASRN — 506-64-9
Last Revised — 01/31/1987

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