Chlorine cyanide (CASRN 506-77-4)
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0024
Chlorine cyanide;
CASRN 506-77-4
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 Chlorine cyanide
File First On-Line 01/31/1987
Category (section) |
Status |
Last Revised |
---|---|---|
Oral RfD Assessment (I.A.) | on-line | 11/01/1995* |
Inhalation RfC Assessment (I.B.) | no data | |
Carcinogenicity Assessment (II.) | no data |
*A comprehensive review of toxicological studies was completed (05/27/05) - 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 — Chlorine cyanide
CASRN — 506-77-4
Primary Synonym — Cyanogen chloride
Last Revised — 11/01/1995
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 |
NOAEL: 10.8 mg/kg/day cyanide converted to 25.3 mg/kg/day of chlorine cyanide |
100
|
5
|
5E-2
mg/kg/day |
Weight loss, thryoid Rat Subchronic to |
LOAEL: 30 mg/kg/day cyanide (70 mg/kg/day C1CN) |
*Conversion Factors -- molecular weight conversion factor = 61/26 [MW ClCN = 61; 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.
Since chloride is present in very high levels physiologically, an RfD of 3.5 mg/day is recommended based on the maximum number of molar equivalents (1) of cyanide (CN) released in aqueous solutions or dilute acids.
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 — 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 — This assessment is not presented in any existing U.S. EPA document.
Other EPA Documentation — None
Agency Work Group Review — 08/05/1985
Verification Date — 08/05/1985
A comprehensive review of toxicological studies published through May 2005 was conducted. No new health effects data were identified that would be directly useful in the revision of the existing RfD for Chlorine cyanide and a change in the RfD is not warranted at this time. For more information, IRIS users may contact 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 — Chlorine cyanide
CASRN — 506-77-4
Primary Synonym — Cyanogen chloride
Not available at this time.
_II. Carcinogenicity Assessment for Lifetime Exposure
Substance Name — Chlorine cyanide
CASRN — 506-77-4
Primary Synonym — Cyanogen chloride
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 — Chlorine cyanide
CASRN — 506-77-4
Primary Synonym — Cyanogen chloride
Last Revised — 08/01/1991
_VI.A. Oral RfD References
Amo, H. 1973. Effects of oral administration of CN and heavy metals in long term on breeding and chromosome 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 in baboons. Toxicology. 12(3): 221-234.
Hertting, G., O. Kraupp, E. Schnetz and St. Wuketich. 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(4): 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.
_VI.B. Inhalation RfC References
None
_VI.C. Carcinogenicity Assessment References
None
_VII. Revision History
Substance Name — Chlorine cyanide
CASRN — 506-77-4
Primary Synonym — Cyanogen chloride
Date |
Section |
Description |
---|---|---|
03/31/1987 | I.A.6. | Documentation corrected |
09/01/1990 | IV.F.1. | EPA contact changed |
09/01/1990 | VI. | Bibliography on-line |
08/01/1991 | VI.A. | Amo, 1973 & Hertting et al. 1960 references clarified |
01/01/1992 | I.A.7. | Primary contact changed |
01/01/1992 | IV. | Regulatory actions updated |
11/01/1995 | 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. |
10/28/2003 | I.A.6. | Screening-Level Literature Review Findings message has been added. |
06/22/2005 | I.A.6. | Screening-Level Literature Review Findings message has been removed and replaced by comprehensive literature review conclusions. |
_VIII. Synonyms
Substance Name — Chlorine cyanide
CASRN — 506-77-4
Primary Synonym — Cyanogen chloride
Last Revised — 01/31/1987
- 506-77-4
- CHLORCYAN
- Chlorine Cyanide
- CHLOROCYAN
- CHLOROCYANIDE
- CHLOROCYANOGEN
- CHLORURE DE CYANOGENE
- Cyanogen chloride
- RCRA WASTE NUMBER P033
- UN 1589