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Chlorine cyanide
CASRN 506-77-4
Contents
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 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
_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 100 5 5E-2
Study cyanide converted to mg/kg/day
25.3 mg/kg/day of
Howard and Hanzal, chlorine cyanide
1955
Weight loss, thyroid LOAEL: 30 mg/kg/day
effects and myelin cyanide
degeneration (70 mg/kg/day ClCN)
Rat Subchronic to
Chronic Oral Bioassay
Philbrick et al., 1979
*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 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
Data Base -- 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 data base 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
___I.A.7. EPA CONTACTS (ORAL RfD)
Please contact the Risk Information Hotline for all questions concerning this
assessment or IRIS, in general, at (513)569-7254 (phone), (513)569-7159 (FAX)
or RIH.IRIS@EPAMAIL.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.
_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
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
Last updated: 5 May 1998
URL: http://www.epa.gov/iris/SUBST/0024.HTM
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