Cyanogen (CASRN 460-19-5)
view QuickView

0032
Cyanogen;
CASRN 460-19-5
Health assessment information on a chemical substance is included in IRIS
only after a comprehensive review of chronic toxicity data by U.S. EPA
health scientists from several Program Offices and the Office of Research
and Development. The summaries presented in Sections I and II represent
a consensus reached in the review process. Background information and
explanations of the methods used to derive the values given in IRIS are
provided in the Background Documents.
STATUS OF DATA FOR Cyanogen
File First On-Line 01/31/1987
Category (section) |
Status |
Last Revised |
---|---|---|
Oral RfD Assessment (I.A.) | on-line | 12/01/1989 |
Inhalation RfC Assessment (I.B.) | no data | |
Carcinogenicity Assessment (II.) | no data |
_I. Chronic Health Hazard Assessments for Noncarcinogenic Effects
_I.A. Reference Dose for Chronic Oral Exposure (RfD)
Substance Name — Cyanogen
CASRN — 460-19-5
Last Revised — 12/01/1989
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
|
---|---|---|---|---|
No adverse effects Howard and Hanzal, 1955 |
NOAEL: 10.8 mg/kg/day cyanide converted to 21.6 mg/kg/day of cyanogen |
100
|
5
|
4E-2
mg/kg/day |
Weight loss, thyroid Rat Subchronic to Philbrick et al., 1979 |
LOAEL: 30 mg/kg/day |
*Conversion Factors -- molecular weight conversion factor = 52/26 [MW C2N2 = 52; MW CN = 26]
__I.A.2. Principal and Supporting Studies (Oral RfD)
Howard, J.W. and R.F. Hanzal. 1955. Chronic toxicity for rats of 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.
The toxicity of cyanogen, itself, has not been assessed. This risk assessment is based on the toxicity of the cyanide (CN) ion. Cyanogen does not completely dissociate into free cyanide in water or dilute acetic acid. The RfD for this compound is derived from the RfD of free cyanide on an equimolar basis, assuming that cyanogen releases only one molar equivalent of free cyanide.
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; Hertting et al., 1960). Human data do not provide adequate information from which to derive an RfD because effective dose levels of chronically ingested cyanide are not documented. Therefore, the study of Howard and Hanzel (1955) provides the highest NOAEL, 10.8 mg/kg/day for cyanide, and is chosen for the derivation of an RfD for cyanide 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 gilts. 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 — Medium
RfD — Medium
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 medium because a small but sufficient number of studies support the chosen study. Medium confidence in the RfD follows. Additional 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, 1985
Other EPA Documentation — None
Agency Work Group Review — 08/05/1985
Verification Date — 08/05/1985
Screening-Level Literature Review Findings — A screening-level review conducted by an EPA contractor of the more recent toxicology literature pertinent to the RfD for Cyanogen conducted in September 2002 did not identify any critical new studies. IRIS users who know of important new studies may provide that information to the IRIS Hotline at hotline.iris@epa.gov or (202)566-1676.
__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).
_I.B. Reference Concentration for Chronic Inhalation Exposure (RfC)
Substance Name — Cyanogen
CASRN — 460-19-5
Not available at this time.
_II. Carcinogenicity Assessment for Lifetime Exposure
Substance Name — Cyanogen
CASRN — 460-19-5
This substance/agent has not undergone a complete evaluation and determination under US EPA's IRIS program for evidence of human carcinogenic potential.
_III.
[reserved]
_IV. [reserved]
_V. [reserved]
_VI. Bibliography
Substance Name — Cyanogen
CASRN — 460-19-5
Last Revised — 12/01/1989
_VI.A. Oral RfD References
Amo, H. 1973. Effects of oral administration of cyanide and heavy metals in long term on breeding and chromosome analyses of mice. Nagoya Shiritsu Diagaku Igakkai Zasshi. 24(1): 48-66.
Crampton, R.E., I.F. Gaunt, R. Harris et al. 1979. Effect of low cobalamin diet and chronic cyanide toxicity in baboons. Toxicology. 12: 221-234.
Hertting, G., O. Kraupp, E. Schnetz and S. Weeketich. 1960. Untersuchungen uber die folgen einer chronischen verabreichung akut toxischer dosen von naturimcyanid. 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 neuropathy. Arch. Opthalmol. 86: 194-204.
Philbrick, D.J., J.B. Hopkins, D.C. Hill, J.C. Alexander and R.G. Thomson. 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 (KCN) 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. Vet. Sci. 30: 147-151.
U.S. EPA. 1985. Drinking Water Criteria Document for Cyanide. Prepared by the Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Drinking Water, Washington, DC. (Final draft)
_VI.B. Inhalation RfC References
None
_VI.C. Carcinogenicity Assessment References
None
_VII. Revision History
Substance Name — Cyanogen
CASRN — 460-19-5
Date |
Section |
Description |
---|---|---|
03/31/1987 | I.A.6. | Documentation corrected |
03/01/1988 | I.A.5. | Confidence levels revised |
12/01/1989 | I.A.1. | Critical effect clarified |
12/01/1989 | I.A.2. | Co-principal study added |
12/01/1989 | I.A.6. | EPA documentation added |
12/01/1989 | VI. | Bibliography on-line |
01/01/1992 | I.A.7. | Primary contact changed |
01/01/1992 | IV. | Regulatory action updated |
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. |
_VIII. Synonyms
Substance Name — Cyanogen
CASRN — 460-19-5
Last Revised — 01/31/1987
- 460-19-5
- CARBON NITRIDE
- Cyanogen
- CYANOGENE
- DICYAN
- DICYANOGEN
- ETHANEDINITRILE
- NITRILOACETONITRILE
- OXALIC ACID DINITRILE
- OXALIC NITRILE
- OXALONITRILE
- OXALYL CYANIDE
- PRUSSITE
- RCRA WASTE NUMBER P031
- UN 1026