EPA-540/1-86-012
Agency
Office of Emergency and
Remedial Response
Washington DC 20460
Off'ce of Research and Development
Office of Health and Environmental
Assessment
Environmental Criteria and
Assessment Office
Cincinnati OH 45268
Superfund
vvEPA
'HEALTH EFFECTS ASSESSMENT
FOR SODIUM CYANIDE
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EPA/540/1-86-012
September 1984
HEALTH EFFECTS ASSESSMENT
FOR SODIUM CYANIDE
U.S. Environmental Protection Agency
Office of Research and Development
Office of Health and Environmental Assessment
Environmental Criteria and Assessment Office
Cincinnati, OH 45268
U.S. Environmental Protection Agency
Office of Emergency and Remedial Response
Office of Solid Waste and Emergency Response
Washington, DC 20460
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DISCLAIMER
This report has been funded wholly or In part by the United States
Environmental Protection Agency under Contract No. 68-03-3112 to Syracuse
Research Corporation. It has been subject to the Agency's peer and adminis-
trative review, and It has been approved for publication as an EPA document.
Mention of trade names or commercial products does not constitute endorse-
ment or recommendation for use.
11
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PREFACE
This report summarizes and evaluates Information relevant to a prelimi-
nary interim assessment of adverse health effects associated with sodium
cyanide. All estimates of acceptable intakes and carcinogenic potency
presented 1n this document should be considered as preliminary and reflect
limited resources allocated to this project. Pertinent toxlcologic and
environmental data were located through on-line literature searches of the
Chemical Abstracts, TOXLINE, CANCERLINE and the CHEMFATE/DATALOG data bases.
The basic literature searched supporting this document is current up to
September, 1984. Secondary sources of Information have also been relied
upon in the preparation of this report and represent large-scale health
assessment efforts that entail extensive peer and Agency review. The
following Office of Health and Environmental Assessment (OHEA) sources have
been extensively utilized:
U.S. EPA. 1980a. Ambient Water Quality Criteria for Cyanides,
with Errata for Ambient Water Quality Criteria Documents dated June
9, 1981 (updated February 23, 1982). Prepared by the Environmental
Criteria and Assessment Office, Cincinnati, OH, OHEA for the Office
of Water Regulations and Standards, Criteria and Standards Divi-
sion, Washington, DC. EPA 440/5-80-035. NTIS PB 81-117483.
U.S. EPA. 1985. Drinking Water Criteria Document for Cyanide.
Prepared by the Environmental Criteria and Assessment Office,
Cincinnati, OH, OHEA for the Office of Drinking Water, Washington,
DC. Final draft.
The intent in these assessments 1s to suggest acceptable exposure levels
whenever sufficient data were available. Values were not derived or larger
uncertainty factors were employed when the variable data were limited in
scope tending to generate conservative (I.e., protective) estimates. Never-
theless, the interim values presented reflect the relative degree of hazard
associated with exposure or risk to the chemical(s) addressed.
Whenever possible, two categories of values have been estimated for sys-
temic toxicants (toxicants for which cancer is not the endpoint of concern).
The first, the AIS or acceptable intake subchronlc, is an estimate of an
exposure level that would not be expected to cause adverse effects when
exposure occurs during a limited time Interval (i.e., for an interval that
does not constitute a significant portion of the Hfespan). This type of
exposure estimate has not been extensively used or rigorously defined, as
previous risk assessment efforts have been primarily directed towards
exposures from toxicants in ambient air or water where lifetime exposure is
assumed. Animal data used for AIS estimates generally include exposures
with durations of 30-90 days. Subchronic human data are rarely available.
Reported exposures are usually from chronic occupational exposure situations
or from reports of acute accidental exposure.
111
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The AIC, acceptable Intake chronic, 1s similar 1n concept to the ADI
(acceptable dally Intake). It 1s an estimate of an exposure level that
would not be expected to cause adverse effects when exposure occurs for a
significant portion of the Hfespan [see U.S. EPA (1980b) for a discussion
of this concept]. The AIC Is route specific and estimates acceptable
exposure for a given route with the Implicit assumption that exposure by
other routes Is Insignificant.
Composite scores (CSs) for noncarcinogens have also been calculated
where data permitted. These values are used for ranking reportable quanti-
ties; the methodology for their development 1s explained 1n U.S. EPA (1983).
For compounds for which there 1s sufficient evidence of cardnogenlcHy,
AIS and AIC values are not derived. For a discussion of risk assessment
methodology for carcinogens refer to U.S. EPA (1980b). Since cancer 1s a
process that 1s not characterized by a threshold, any exposure contributes
an Increment of risk. Consequently, derivation of AIS and AIC values would
be Inappropriate. For carcinogens, q-j*s have been computed based on oral
and Inhalation data 1f available.
1v
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ABSTRACT
In order to place the risk assessment evaluation 1n proper context,
refer to the preface of this document. The preface outlines limitations
applicable to all documents of this series as well as the appropriate Inter-
pretation and use of the quantitative estimates presented.
Adequate data are available for experimental animals orally exposed to
cyanide. The various studies agree well 1n terms of suggesting a NOEL.
U.S. EPA (1985) has calculated a NOEL of 10.8 mg CNVkg for female rats
exposed to cyanide 1n their food as a basis for estimating acceptable
exposure levels (Howard and Hanzal, 1955). By analogy, an AIC for NaCN of
2.8 mg/day for a 70 kg human Is calculated. A CS of 11.4, based on CNS
lesions 1n dogs treated by capsule with NaCN was calculated.
Data for effects following Inhalation exposure to CN~ are extremely
limited. An AIC has been estimated based on the TLV of 5 mg/m3 but should
not be adopted because of presumed greater toxldty due to exposure by the
Inhalation route.
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ACKNOWLEDGEMENTS
The Initial draft of this report was prepared by Syracuse Research
Corporation under Contract No. 68-03-3112 for EPA's Environmental Criteria
and Assessment Office, Cincinnati, OH. Dr. Christopher DeRosa and Karen
Blackburn were the Technical Project Monitors and Helen Ball was ,the Project
Officer. The final documents In this series were prepared for the Office of
Emergency and Remedial Response, Washington, DC.
Scientists from the following U.S. EPA offices provided review comments
for this document series:
Environmental Criteria and Assessment Office, Cincinnati, OH
Carcinogen Assessment Group
Office of A1r Quality Planning and Standards
Office of Solid Waste
Office of Toxic Substances
Office of Drinking Water
Editorial review for the document series was provided by:
Judith Olsen and Erma Durden
Environmental Criteria and Assessment Office
Cincinnati, OH
Technical support services for the document series was provided by:
Bette Zwayer, Pat Daunt, Karen Mann and Jacky Bohanon
Environmental Criteria and Assessment Office
Cincinnati, OH
v1
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TABLE OF CONTENTS
1.
2.
3.
4.
5.
ENVIRONMENTAL CHEMISTRY AND FATE
ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS . . .
2.1.
2.2.
ORAL
INHALATION
TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
3.1.
3.2.
3.3.
3.4.
SUBCHRONIC
3.1.1. Oral
3.1.2. Inhalation
CHRONIC
3.2.1. Oral
3.2.2. Inhalation
TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS. . . .
3.3.1. Oral
3.3.2. Inhalation
TOXICANT INTERACTIONS
CARCINOGENICITY
4.1.
4.2.
4.3.
4.4.
HUMAN DATA
4.1.1. Oral
4.1.2. Inhalation
BIOASSAYS
4.2.1. Oral
4.2.2. Inhalation
OTHER RELEVANT DATA
WEIGHT OF EVIDENCE
REGULATORY STANDARDS AND CRITERIA
Page
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... 4
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... 7
... 8
... 8
. . . . 11
... 11
. . . . 11
... 11
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... 13
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... 15
V11
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TABLE OF CONTENTS (cont.)
Page
6. RISK ASSESSMENT 17
6.1. ACCEPTABLE INTAKE SUBCHRONIC (AIS) 17
6.1.1. Oral 17
6.1.2. Inhalation 17
6.2. ACCEPTABLE INTAKE CHRONIC (AIC) 17
6.2.1. Oral 17
6.2.2. Inhalation 20
6.3. CARCINOGENIC POTENCY (q-j*) 21
6.3.1. Oral 21
6.3.2. Inhalation 21
7. REFERENCES 22
APPENDIX: Summary Table for Sodium Cyanide 32
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LIST OF TABLES
No. Title Page
3-1 Subchronlc Tox1c1ty of Orally Administered Cyanide 5
3-2 Representative Control Studies of Occupational Exposure
by Inhalation or Dermal Routes 9
3-3 Chronic Toxldty of Orally Administered Cyanide 10
5-1 Tolerances for Hydrogen Cyanide 1n Foodstuffs when Used
as a Post-Harvest Fumlgant 16
1x
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LIST OF ABBREVIATIONS
ADI Acceptable dally Intake
AIC Acceptable Intake chronic
AIS Acceptable Intake subchronlc
BCF B1oconcentrat1on factor
bw Body weight
CAS Chemical Abstract Service
CNS Central nervous system
CS Composite score
GI Gastrointestinal
Kow Octanol/water partition coefficient
1050 Dose lethal to 50% of recipients
LOAEL Lowest-observed-adverse-effect level
MED Minimum effective dose
RNA Rlbonuclelc acid
RV(j Dose-rating value
RVe Effect-rating value
TLV Threshold limit value
TWA Time-weighted average
UF Uncertainty factor
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1. ENVIRONMENTAL CHEMISTRY AND FATE
The relevant physical and chemical properties for sodium cyanide are
given below.
Chemical class: Inorganic cyanide
Molecular weight: 49.01
Vapor pressure: 0.76 mm Hg at 800°C
(Towlll et al., 1978)
Water solubility: 48 g/100 m«. at 10°C
(Weast, 1980)
Log octanol/water
partition coefficient: 0.44 (estimated)
BCF: 0.27 (estimated)
The value for the K has been estimated by the method of Leo et al.
(1971) from the value given by Hansch and Leo (1979). The value of 0.27 for
the BCF has been estimated from the log K value given above and the
equation of Velth et al. (1979).
The atmospheric fate of sodium cyanide has not been comprehensively
studied. The most likely chemical reaction for sodium cyanide In the
atmosphere Is heterogenous reaction with OH» radicals. Considering the
half-life of the homogenous hydrogen cyanide reaction with OH« radicals
(Graedel, 1978), 1t appears unlikely that sodium cyanide will have any
significant chemical loss mechanism In the troposphere. The primary removal
process for atmospheric sodium cyanide appears to be physical. Both dry
deposition and wet deposition may dominate the fate of sodium cyanide 1n the
atmosphere, although, considering the aqueous solubility of sodium cyanide,
the latter process appears to be more Important than the former process.
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Sodium cyanide may be lost from aquatic media primarily through the
volatilization process (Callahan et al.. 1979). Sodium cyanide at low
concentrations may undergo some blodegradatlon, but blodegradatlon 1s likely
to be far less significant in determining the fate of sodium cyanide 1n
aquatic media (Callahan et al., 1979). Similarly, because of Us low
tendency to adsorb onto sediments, sorptlon may not be an Important process
for sodium cyanide in aquatic media (Callahan et al., 1979).
The fate of sodium cyanide In soil 1s Inadequately studied. To draw an
analogy from its expected fate in water, 1t is likely that the fate of
sodium cyanide in soil may be pH dependent. In acidic soils, the loss of
hydrogen cyanide through volatilization may be the predominant mechanism
from soil surfaces. In subsurface soil, sodium cyanide present in small
concentrations (below the toxic levels for microorganisms) may undergo some
mlcrobial degradation (Callahan et al., 1979), and a part may leach through
the soil because of Us high water solubility and low soil sorptlon charac-
teristics. In basic soils, the mobility of sodium is expected to be greatly
restricted.
The simple metal cyanides, such as sodium cyanide, are not expected to
bioaccumulate 1n aquatic organisms (U.S. EPA, 1980a). As can be seen from
the selected physical and chemical properties for sodium cyanide, the
estimated value of 0.27 for the BCF for sodium cyanide 1s In conformity with
the U.S. EPA (1980a) prediction.
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2. ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS
2.1. ORAL
Cyanide 1s readily absorbed by the 61 tract. Yamamoto et al. (1982)
exposed rats orally by gavage to either 7 or 21 mg NaCN/kg bw. Following
treatment and subsequent death (minutes later), levels of cyanide 1n the
blood were 5.01+1.61 and 4.79+2.04 pg/ms, for the low-dose and high-dose,
respectively. This Indicates that sodium cyanide 1s readily absorbed by the
61 tract. 6ettler and Balne (1938) exposed dogs to potassium cyanide
equivalent to 1.57, 4.42 or 8.42 mg HCN/kg bw by gavage. Upon death (155,
21 and 8 minutes post-treatment), the amount of hydrogen cyanide remaining
1n the 61 tract was measured and subtracted from the amount administered;
this was considered to be equivalent to the amount absorbed, and was 72, 24
and 16.6% for dogs receiving 1.57, 4.42 and 8.42 mg/kg, respectively.
2.2. INHALATION
Pertinent data regarding the absorption of sodium cyanide by Inhalation
could not be located 1n the available literature.
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3. TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
3.1. SUBCHRONIC
3.1.1. Oral. In evaluating studies regarding the oral toxldty of
cyanide, factors affecting the rate of absorption may be as Important as the
dose administered (U.S. EPA, 1985). Cyanide 1s metabolized rapidly by the
liver to thlocyanate, an enzymatic rate-saturable reaction. Factors that
enhance absorption may result 1n severe toxic manifestations from a dose
that ordinarily would not cause toxldty, because the ability of the Hver
to metabolize cyanide as a first pass phenomenon had been exceeded. The
volume of the Intestinal contents and rate of peristalsis are factors that
affect the rate of GI absorption. It may also be expected that toxldty
would be more likely 1f cyanides are given as a bolus rather than 1n smaller
allquots throughout the day.
Another Important consideration regarding dietary studies 1s the propen-
sity for cyanide to volatilize from treated foodstuffs, resulting 1n a lack
of toxic manifestations at potentially dangerous levels (U.S. EPA, 1985).
Also, animals (and presumeably humans) can successfully withstand higher
doses of cyanide when administered 1n the diet rather than by Inhalation,
because of the first pass conversion of orally administered cyanide to
thlocyanate (detoxification) In the Hver when 1t 1s orally administered.
Because of the expected similarities 1n the toxldty of sodium cyanide
and other cyanides, studies with other cyanides are Included 1n the toxldty
sections.
Data regarding the subchronlc toxldty of orally administered cyanide
are summarized 1n Table 3-1. Palmer and Olson (1979) reported significantly
higher liver weights In adult rats exposed to 200 mg KCN/8. drinking water,
but no effect on liver weight when potassium cyanide was administered as 200
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TABLE 3-1
Subchronlc Toxlclty of Orally Administered Cyanide
Species/ Number/Sex
Height or Age
Rat/70 g 7H/group
7H/group
Rat/adult NR
NR
Rat/weanling BMW /group
African giant rat/ 6N and 2F/
weanllng/~90 g group
Plg/weanllng 1H and IF
Dose of Compound
0 and 200 mg
KCN/t
drinking water
0 and 200 mg
KCN/kg diet
0. 10 mg KCN/kg
bw/day In diet
0-250 mg KCN/kg
bw/day In diet
0, 1875 mg
KCN/kg diet
0. 2500 mg
KCN/kg diet
0, 1875 mg
KCN/kg diet
Dosea as CN-
0 and 80 mg/l
(8 rog/kg
bw/day)
0 and 80 tag/kg
diet (4 mg/kg
bw/day)
0. 4 mg/kg
bw/day
0-100 mg/kg
bw/day
0. 750 mg/kg
diet (37.5
mg/kg bw/day)
0. 1000 mg/kg
diet (36 mg/kg
bw/day )b
0. 750 mg/kg
d1et(~30 mg/kg
bw/day )b
Period of
Exposure
21 days
21 days
25 days
90 days
56 days
84 days
56 days
Effects
Treated animals: significantly
Increased (p<0.05) liver
weights (15.8 g), compared
with controls (13.5 g). No
effect on body weight.
Treated animals: no Increase
In liver weights (13.7 g).
compared with controls (13.5 g).
No effect on body weight.
No mortality.
No mortality; this dose was 25
times the acute oral 1059 for
rats. Animals tolerated CN~
better when It was mixed In
feed.
No effect on body weight, ratio
of liver and kidney weight to
body weight, food consumption,
or protein efficiency ratio.
Treated animals: slight
reduction In food consumption
and weight gain, compared
with controls. No hlstopatho-
loglcal changes In spleen,
liver, kidney or thymus.
Treated animals: small but
significant reduction In food
consumption (p<0.05), compared
Reference
Palmer and
Olson. 1979
Hayes. 1967
Tewe and
Haner. 1982
Tewe, 1982
Tewe and
Haner. 1980
with controls. No effect on body
weight, food efficiency ratio,
protein efficiency ratio, or
ratio of various organ weights
(spleen, liver, kidney, heart,
thyroid) to body weight. No
hlstopathologlcal changes.
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TABLE 3-1 (cont.)
cr
i
Species/
Weight or Age
Dog/7.6 kg
Dog/NR
Number/Sex
1 control,
3 treated
(sex NR)
1 control,
3 treated
(sex NR)
Dose of Compound
0. 500 ppm NaCN
In diet
NaCN at 0, 0.5.
1.0 up to 2x2.0
ing/kg bu/day by
capsule
Dosea as CM- Period of
Exposure
3 mg/kg bw/day 30-32 days
0. 0.27. 0.53 up 15 months
to 2x1.1 ing/kg
bw/day (average
3 mg/kg bw/day
In high group)
Effects
No effects on food consumption,
body weight gain, hematology,
gross or microscopic pathology
Toxlclty observed In high group:
acute toxlclty Immediately after
dosing, full recovery In <0.5
hours. All treated dogs:
degeneration of ganglion and
Purklnje cells of CNS
Reference
American
Cyanamld
Co., 1959
Her t ting
et al., 1960
aValues In parentheses were calculated as follows:
1) For CN- In the diet, the dose In mg/kg/dlet Is multiplied by the fraction of body weight consumed by a rat/day (0.05).
2) For CN- In the water, the dose In mg/t Is multiplied by the average amount of t^O consumed by a rat/day (0.035 I/day), and
divided by the weight of the rat (If unknown. It Is assumed to be 0.35 kg), e.g., rats assumed to drink water equivalent to 10X of
their body weight/day.
Calculated by U.S. EPA (1985) from body weight and food consumption data provided by Investigators.
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mg/kg diet. Tewe (1982) and Tewe and Maner (1980, 1982) treated weanling
pigs and rats with potassium cyanide, and observed only a slight reduction
1n food consumption with no other effects. Hayes (1967) reported that adult
rats could tolerate 25 times the LD5Q dose of potassium cyanide when H
was administered 1n the diet. When given 1n the diet, NaCN at 3 mg CN"/kg
bw/day had no effect In dogs (American Cyanamld Co., 1959). The same dosage
given by capsule led to signs of acute toxlclty 1n dogs from which recovery
was complete within 0.5 hours (Herttlng et a!., 1960). When given by
capsule to dogs for 15 months, 6 mg NaCN/kg bw/day was sufficient to cause
cellular degeneration 1n the CNS. Although animals In this study were
exposed to a range of potassium cyanide concentrations, these Investigators
only reported mortality.
3.1.2. Inhalation. Only one animal study regarding the subchronlc
toxldty of cyanide was located 1n the available literature. Hugod (1981)
exposed rabbits (22/group) to either 0 or 0.55 mg/m3 hydrogen cyanide In
air. After 28 days, the treated animals were not different from controls 1n
myocardlal ultrastructure.
In humans, exposure to cyanide by Inhalation and dermal routes has been
reported In the metal Industry. Sandberg (1967) reported on a goldsmith
apprentice who polished gold 5-10 times/day for 4 years. The polishing
solution he used was prepared by adding 15 g of potassium cyanide to water,
bringing 1t to a boll, then adding hydrogen peroxide; this process liberated
hydrogen cyanide gas and splattered the skin. Symptoms of toxldty 1n this
man Included headache, Ustlessness, numbness and partial paralysis of his
left arm and leg, and partial loss of vision 1n his left eye. Other cases
1n which similar symptoms have been reported are summarized by NIOSH (1976).
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There have also been reports of goiter associated with occupational exposure
to cyanide (Hardy et al., 1950). In addition, many case-control studies
regarding exposure to cyanide have been reported. Several of these are
summarized 1n Table 3-2.
3.2 CHRONIC
3.2.1. Oral. Data pertaining to the chronic toxldty of orally admin-
istered cyanides are summarized 1n Table 3-3. Howard and Hanzal (1955)
exposed rats to 0, 76, or 190 mg HCN/kg diet (equivalent to 0, 73, 183 mg
CITVkg) for 104 weeks. Animals treated at any level had no signs of
toxldty; no hlstopathologlcal changes 1n the heart, lungs, liver, spleen,
stomach, Intestines, kidney, adrenals, thyroid, reproductive organs, cere-
bellum or cerebrum; and no differences 1n growth rate compared with con-
trols. The only effects of treatment were elevated levels of CfT1 In the
erythrocytes and elevated thlocyanate 1n the blood, liver and kidneys.
PhUbMck et al. (1979) treated groups of 10 male weanling rats with 0
or 1500 mg KCN/kg diet and reported signs of primary myelln degeneration 1n
the spinal cord after 11.5 months treatment. Rats maintained on methlonlne
and vitamin B.? deficient diet appeared to be affected more severely.
With respect to humans, the high Incidence of amblyoplas, thyroid dis-
orders and neuropathies seen in tropical regions of Africa has been associ-
ated with chronic Ingestion of cassava, a dietary staple containing a cyano-
genlc glycoslde that releases hydrogen cyanide when metabolized in vivo
(Monekosso and Wilson, 1966; Osuntokun, 1968, 1972; Osuntokun et al., 1969,
1970; MacKenzie and Phillips, 1968; Makene and Wilson, 1972; Ermans et al.,
1972; Delange and Ermans, 1971). Sufficient data to quantify dose and
effects were not available in these studies.
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TABLE 3-2
Representative Control Studies of Occupational Exposure to Cyanide by Inhalation or Dermal Routes
Study Population
Control Population
Period of
Exposure
Level of Exposure
Effects
Reference
36 male electro-
platers from 3
factories, >30
years of age. all
nonsmokers
13 HCN fumlgators
who had suffered
acute symptoms of
HCN poisoning with
loss of conscious-
ness
31 men, 12 women
In Romanian metal
galvanizing oper-
ation
20 males of com-
parable age and
socloeconomlc
status: non-
smokers not ex-
posed to cyanide
4 HCN fumlgators
who had not re-
ported symptoms of
acute HCN poisoning
NR
5-15 years
1-27 years
0.25-16
years (mean:
5.4 years)
mean concentration
In the breathing
zone: 7.1. 8.9 and
11.5 mg/m' for the
three factories
NR
average exposure
over 5' years:
0.26 mg/m«
Exposed men: headache (29); weakness El Ghawabl
(28); changes In smell and taste (28); et al.. 1975
giddiness (20); throat Irritation (16);
vomiting (16); difficulty breathing
(16); precordlal pain (7); difficulty
focusing eyes (3); psychosis (2). Non-
exposed workers had much lower inci-
dences of these symptoms. Exposed
workers also had significantly higher
(p<0.001) hemoglobin to lymphocyte
counts, and significantly higher
(<0.001) uptake of »"I by the thyroid.
13 symptomatic men: high Incidence of Carmelo. 1955
nervous disorders; precordlal pain (9);
EKG abnormalities (11); hypertroplc
gastritis (11). 4 controls: no stomach
or Intestinal disorders.
Significantly reduced activity of cyto- Dlnca et al.,
chrome oxldase and other redox enzymes. 1972
NR = Not reported
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TABLE 3-3
Chronic Toxlclty of Orally Administered Cyanide
o
I
Species/
Starting Number
Weight
Rat/57 g 10F and
lOM/group
Weanling lOH/group
rat/43 g
Dose of
Compound
0, 76, 190
mg HCN/kg
diet
0, 1500 mg
diet
Dose as CN~
0, 73, 183
mg/kg diet
0, 600 mg/kg
diet
(0.30 mg/kg
bw/day)*
Period
of
Exposure
104
weeks
11.5
months
Effects
No effects with regard
to body weights or hls-
topathologlcal changes
of many organs.
Treated rats: primary
myelln degeneraton and
vacuoles In spinal cord.
Decreased plasma thyroxln
levels at 4 months with
recovery by 11 months.
Reference
Howard and
Hanzal, 1955
Phllbrlck
et al., 1979
*Assum1ng rats eat food equivalent to 554 of their body weight/day.
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3.2.2. Inhalation. Animal studies pertaining to the chronic toxlclty of
Inhaled cyanide could not be located In the available literature. Exposure
to cyanide In tobacco smoke, however, has been associated with tobacco
amblyopla, Leber's hereditary optic atrophy, retrobulbar neuritis and optic
atrophy (Wokes, 1958; Pettlgrew and Fell, 1972, 1973; Wilson and Matthews,
1966; Foulds et al., 1968; Wilson, 1983). These disorders Involve defective
cyanide metabolism (the conversion of cyanide to thlocyanate by rhodanase 1s
defective) and vitamin B,? deficiency.
3.3. TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS
3.3.1. Oral. The reproductive performance of rats fed 500 mg CN"/kg
diet throughout gestation and lactation was unaffected (Tewe and Maner,
1981a). Furthermore, Utter size, weight of the pups at birth, and food
consumption and growth rate of pups after birth were not significantly
different from controls.
In contrast, the fetuses of pigs (9/level) fed 276.6 or 520.7 mg
CN~/kg diet throughout gestation to lactation had reduced organ to body
weight ratios for thyroid, heart and spleen when compared with those born to
pigs fed 30.6 mg CN~/kg diet. Sows treated at all levels had hyperplasia
of the glomerull (Tewe and Maner, 1981b). Teratogenic affects per se were
not reported 1n either of these studies.
3.3.2. Inhalation. Pertinent data regarding the teratogenldty of
Inhaled cyanide could not be located 1n the available literature.
3.4. TOXICANT INTERACTIONS
Since cyanide 1s a known Inhibitor of cytochrome oxldase, compounds such
as sulflde or azlde, which also Inhibit cytochrome oxldase, may synerglze
with cyanide (Nlcholls, 1975; Smith et al.. 1977). Vitamin C may also
enhance the toxlclty of cyanide. Basu (1983) treated a group of guinea pigs
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first with vitamin C, then with potassium- cyanide, and another group only
with potassium cyanide. Vitamin C-treated animals had a 100% Incidence of
severe tremors, ataxla, muscle twitches, paralysis and convulsion. Animals
exposed only to potassium cyanide had a 38% Incidence of these symptoms. It
was hypothesized that vitamin C may tie up cystelne, a sulfur donor poten-
tially Involved 1n the conversion of cyanide to thlocyanate, Its less
harmful metabolite.
Compounds that generate methemoglobln (sodium nitrate, amyl nitrate,
hydroxylamlne or methylene blue) antagonize the toxic effects caused by
cyanide, since methemoglobln competes with cytochrome oxldase for cyanide
(Smith and Olson, 1973; Way, 1981). Cobalt-containing compounds also
antagonize the toxldty of cyanide, since cobalt has an affinity for cyanide
(Mushett et a!., 1952; FMedberg and Schwarzkopf, 1969; Davlson, 1969).
-12-
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4. CARCINOGENICITY
4.1. HUMAN DATA
4.1.1. Oral. Pertinent data regarding the carc1nogen1c1ty of orally
Ingested cyanide (hydrogen cyanide, potassium cyanide or sodium cyanide)
could not be located 1n the available literature.
4.1.2. Inhalation. Pertinent data regarding the cardnogenldty of
Inhaled cyanide could not be located In the available literature.
4.2. BIOASSAYS
4.2.1. Oral. Pertinent data regarding the cardnogenldty of orally
administered cyanide could not be located In the available literature.
4.2.2. Inhalation. Pertinent data regarding the cardnogenldty of
Inhaled cyanide could not be located 1n the available literature.
4.3. OTHER RELEVANT DATA
Of the three mutagenldty studies located 1n the available literature,
two were negative and one was marginally positive.. De Flora (1981) reported
that potassium cyanide was not mutagenlc to five strains of Salmonella
typhlmuMum, regardless of the presence or absence of S-9 (mammalian activa-
tion system). Karube et al. (1981) also reported negative results from a
rec-assay In Bacillus subtlHs. Kushl et al. (1983) reported that hydrogen
cyanide gas was marginally mutagenlc to S. typhlmurlum strain TA100 In the
absence of S-9, but not mutagenlc to strain TA98 1n the presence or absence
of S-9.
Tewe and Maner (1981a) reported that no teratogenlc effects were
observed when Wlstar rats were exposed to 500 ppm of cyanide In the diet
throughout pregnancy; however, Tewe and Maner (1981b) reported that fetuses
of pigs fed 276.6 or 520.7 mg CN (as KCN)/kg diet throughout pregnancy had
reduced ratios of organ weight to body weight. At these levels, sows had
kidney hyperplasla and morphological changes In thyroid cells.
-13-
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4.4. WEIGHT OF EVIDENCE
IARC has not evaluated the risk to humans associated with oral or Inha-
lation exposure to cyanide. Since data are lacking regarding the cardno-
genlclty of cyanides to animals or humans, applying the criteria proposed by
the Carcinogen Assessment Group of the U.S. EPA (Federal Register, 1984) for
evaluating the overall weight of evidence of cardnogenlcity to humans,
cyanide 1s most appropriately designated a Group D-Nqt Classified chemical.
-14-
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5. REGULATORY STANDARDS AND CRITERIA
FAO and WHO have established an Interim ADI for cyanide In food of 3.5
mg/man/day, assuming a 70 kg man (U.S. EPA, 1980a). In the June 9, 1981
Errata for Ambient Water Quality Criteria (U.S. EPA, 1980a), an Interim ADI
of 7.56 mg CN~/day water was established, based on a NOAEL of 10.8 mg/kg/
day derived from the chronic study of Howard and Hanzal (1955) (see Section
3.2.1.). In the calculation of this value, an uncertainty factor of 100 was
used. In addition, an average body weight of 70 kg and consumption of 2 H
water/day and 6.5 g fish/day were assumed.
The U.S. Public Health Service (1962) has recommended that levels of
cyanide 1n water not exceed 0.2 mg/a.
ACGIH (1983) has recommended a TWA-TLV of 5 mg/m3 for cyanides, with
the Indication that dermal absorption may also be Involved. This value 1s
based on Irritation to the respiratory system and 1s Intended to protect
from the effects of chronic exposure to hydrogen cyanide (derived primarily
from the report by El Ghawabl et al., 1975). NIOSH (1976) and OSHA (1981)
have also adopted this value as a recommended standard
Tolerances have been set for residues of hydrogen cyanide when used as a
post-harvest Insecticide fumlgant. Those tolerances have been presented In
Table 5-1 (Code of Federal Regulations, 1982).
-15-
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TABLE 5-1
Tolerances for Hydrogen Cyanide 1n Foodstuffs
When Used as a Post-Harvest Fumigant*
Foodstuff Tolerance
(ppm)
Cereal flours 125
Cereals cooked before eaten 90
Uncooked ham, bacon, sausage 50
Cocoa 200
Several spices 250
Several grains 75
Dried beans, peas, nuts 25
*Source: Code of Federal Regulations, 1982
-16-
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6. RISK ASSESSMENT
6.1. ACCEPTABLE INTAKE SUBCHRONIC (AIS)
6.1.1. Oral. Data from animal studies are Insufficient for the calcula-
tion of an AIS for subchronlc oral exposure to sodium cyanide. In the
studies by Palmer and Olson (1979), Tewe and Maner (1980, 1982) and Tewe
(1982), animals were exposed to only one level of treatment In addition to
the control level of exposure (0 mg KCN/kg diet). Furthermore, Palmer and
Olson (1979) reported an Increase 1n liver weight In animals exposed to 4
mg/kg bw/day 1n the diet, but no effect on animals exposed to the same dose
1n drinking water. While Hayes (1967) exposed rats to a range of doses
(0-250), he reported only mortality. Effect levels cannot be established
from these studies.
6.1.2. Inhalation. Only one subchronlc animal study pertaining to
cyanide exposure (Hugod, 1981) was located 1n the available literature. In
this study, rabbits were exposed to a single level of hydrogen cyanide gas
for only 28 days. Furthermore, the human occupational exposure studies are
lacking 1n quantitative detail. Therefore, these studies cannot be used In
quantitative risk assessment.
6.2. ACCEPTABLE INTAKE CHRONIC (AIC)
6.2.1. Oral. The U.S. EPA (1985) has recently reevaluated the data from
the Howard and Hanzal (1955) 2-year experiment with HCN In rats and used
these data to calculate an ADI for CN~. The Drinking Water Criteria Docu-
ment for Cyanide (U.S. EPA, 1985) contains an 1n-depth discussion of the
assumptions and calculations used 1n derivation of the ADI. This discussion
1s presented here In abbreviated form.
The U.S. EPA (1985) chose to derive an ADI for CN~ rather than HCN
because CN~ 1s presumed to be the toxic moiety 1n cyanide compounds.
-17-
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In determining the doses of CN~ to which the rats 1n this study were
exposed on a mg/kg bw/day basis, the average body weights were estimated
using the mean body weights at the beginning and end of the experiment and
the growth charts provided by the Investigators. Average body weights
arrived at by the U.S. EPA (1985) were 390 g and 394 g 1n low- and high-dose
males and 232 g and 255 g 1n low- and high-dose females, respectively. Food
consumption was measured by the Investigators and averaged 19.46 g and 18.50
g/rat/day 1n the low- and high-dose males and 14.69 g and 17.24 g/rat/day In
the low- and high-dose females, respectively. The diets were prepared by
fumigation and HCN was measured 1n the food offered to the rats. From these
data, averaged over the entire treatment period, the U.S. EPA (1985) calcu-
lated that the low-dose diet contained 73 ppm CN~ and the high-dose diet,
160 ppm CN~.
From the above data, the U.S. EPA (1985) calculated the animal doses of
CN~, expressed as mg/kg/day, for the male and female rats In the low- and
high-dose groups as follows:
low-dose male:
73 mg CN~/kg diet x 0.01946 kg diet/0.39 kg bw=3.6 mg CN~/kg bw/day
high-dose male:
160 mg CN"/kg diet x 0.01850 kg diet/0.394 kg bw=7.5 mg CN~/kg bw/day
low-dose female:
73 mg CN~/kg diet x 0.01469 kg diet/0.232 kg bw=4.6 mg CN~/kg bw/day
high-dose female:
160 mg ClT/kg diet x 0.01724 kg diet/0.255 kg bw=10.8 mg CN~/kg bw/day
-18-
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Since effects were not observed 1n treated rats, the animal dose of 10.8 mg
CN~/kg bw/day calculated for high dose females represents the highest
NOEL. The U.S. EPA caluclated an ADI of 1.5 mg CN'/day for a 70 kg human
by multiplying the animal dose, 10.8 CN~/kg bw/day by 70 kg and dividing
by a UF of 500. This corresponds to an ADI for NaCN of 2.8 by multiplying
the ADI for CN~ by the ratio of the formula weight of NaCN (49.01) to
CN~ (26.02). A UF of 500 was chosen as follows: a factor of 10 to
account for animal to human extrapolation, a factor of 10 to afford greater
protection for unusually sensitive Individuals and a final factor of 5
because a criterion for drinking water was derived from a dietary study.
Measurements by the Investigators demonstrated that HCN volatilized from the
diet prepared by fumigation. It was believed that the final UF of 5 may
adjust for the uncertainty associated with volatilization of HCN from the
diet. The U.S. EPA (1985) also suggested that absorption of CN~ from
drinking water might be facilitated but that absorption from the diet may be
retarded by adsorption to food particles. The additional UF of 5 was also
Intended to account for some of the uncertainty associated with this
phenomenon. Since this ADI (2.8 mg NaCN/day for a 70 kg human) was derived
by analogy from data processed by the U.S. EPA (1985) based on the most
complete chronic data available and by a rationale that logically addressed
the Issues Involved 1n risk assessment, this ADI Is adopted as the AIC for
NaCN 1n this document.
A CS was calculated for the effects observed (degeneration of ganglion
cells 1n the CNS) 1n the study by Meriting et al. (1960) using dogs treated
by capsule for 15 months with NaCN at 6 mg NaCN/kg bw/day. A human MED was
calculated by multiplying the animal dose by the cube root of the ratio of
the body weight of dogs (assumed: 14 kg) to that of humans (assumed:
-19-
-------
70 kg) and multiplying the result by 70 kg to express the MED In mg/day for
a 70 kg man. A human MED of 245.6 mg/day, corresponding to an RVd of 1.9,
was calculated. The effects observed were assigned an RV of 6, because
lesions were observed that were not reported to cause a decrement 1n organ
function. A CS of 11.4 was calculated as the product of RV. and RVg.
Although limited data using dogs (Herttlng et al., 1960) suggest a lower
effect level, the dog has been questioned as an appropriate model (U.S. EPA,
1985). The dog 1s especially susceptible to CN~ poisoning, presumably due
to low levels of hepatic rhodaneese, an enzyme Involved In the primary
detoxification pathway for cyanide.
6.2.2. Inhalation. Only one subchronlc study pertaining to exposure to
cyanide by Inhalation (Hugod, 1981) was located 1n the available literature.
Since this study Involved exposure of rabbits for only 28 days, derivation
of an AIC for chronic exposure from these data would be Imprudent. The TLV
of 5 mg/m3 established by ACGIH (1983), however, can be used to derive an
Interim ADI 1n the following manner. Assuming that a 70 kg man breathes a
volume of 10 m3 a1r/8-hour workday and works 5 days/week, the TLV of 5
mg/m3 1s multiplied by the product of 10 mVday and 5/7 days/week to
arrive at an Inhaled dose of 35.7 mg CN~/man/day. Dividing this value by
an uncertainty factor of 10 to account for the range of sensitivities 1n the
human population results 1n an Interim ADI of 3.57 mg CN~/man/day.
This ADI (3.57 mg CN~/man/day) Is larger than the ADI derived for oral
exposure to CN" by the U.S EPA (1985). Since cyanide Is readily absorbed
by the pulmonary system and since the first pass effect of the liver (very
Important 1n CN~ detoxification) Is bypassed by this route, It 1s strongly
recommended that the ADI derived from the TLV not be adopted as an Inhala-
tion ADI for CN".
-20-
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6.3. CARCINOGENIC POTENCY (q.,*)
6.3.1. Oral. The lack of data regarding the carclnogenldty of Ingested
cyanide precludes assessment of carcinogenic risk.
6.3.2. Inhalation. The lack of data regarding the carclnogenldty of
Inhaled cyanide precludes assessment of carcinogenic risk.
-21-
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7. REFERENCES
ACGIH (American Conference of Governmental Industrial Hyglenlsts). 1983.
Threshold Limit Values for Chemical Substances and Physical Agents 1n the
the Workroom Environment with Intended Changes for 1983-1984. Cincinnati,
OH. p. 16.
American Cyanamld Co. 1959. Report on sodium cyanide 30 day repeated feed-
Ing to dogs. Central Med. Dept. Report Number 59-14. (Cited In U.S. EPA,
1985)
Basu, T.K. 1983. High-dose ascorbic add decreases detoxification of
cyanide derived from amygdalln (laetMle): Studies In guinea pigs. Can. J.
Physlol. Pharmacol. 61(11): 1426-1430. (Cited In U.S. EPA, 1985)
Callahan, M.A., M.W. SUmak, N.W. Gabel, et al. 1979. Water-Related
Environmental Fate of 129 Priority Pollutants, Vol. 1. U.S. EPA, Office of
Water Planning and Standards, Office of Water and Waste Management, Washing-
ton, DC. EPA 440/4-79-02923.
Carmelo, S. 1955. New contributions to the study of subacute-chronlc
hydrocyanic add Intoxication 1n man. Rass Med. Ind. 24: 254-271. (Cited
In U.S. EPA, 1985)
Carson, B.L., L.H. Baker, B.L. Herndon, H.V. Ellis and E.M. Horn. 1981.
Hydrogen Cyanide Health Effects. Prepared by Midwest Research Inst., Kansas
City, MO. EPA 460/3-81-026. NTIS PB 82-116039.
-22-
-------
Code of Federal Regulations. 1982. Hydrogen cyanide. 21 CR1 93.236.
Davlson, V. 1969. Cyanide poisoning. Occup. Health. 21: 306-308. (Cited
In U.S. EPA, 1985)
De Flora, S. 1981. Study of 106 organic and Inorganic compounds 1n the
Sa Imone 11 a/micros ome test. Cardnogenesls J. (London). 2(4): 283-298.
(Cited 1n U.S. EPA, 1985)
Oelange, F. and A.M. Ermans. 1971. Role of a dietary goltrogen 1n the
etiology of endemic goiter on Idjwl Island. Am. J. CUn. Nutr. 24:
1354-1360. (Cited 1n U.S. EPA, 1985)
D1nca, C., L. Pod and I. GaletaMu. 1972. Considerations on leukocytlc
oxldatlve enzyme changes 1n subjects exposed to prolonged action of cyan-
hydrlc add 1n Industry. Med. Int. 24: 1385-1395. (CHed In U.S. EPA,
1985)
El Ghawabl, S.H., M.A. Goofar, A.A. El-Sahart1, S.H. Aimed, K.K. Malash and
R. Fares. 1975. Chronic cyanide exposure: a clinical, radlolsotope and
laboratory study. Br. J. Ind. Med. 32: 215-219. (CHed 1n U.S. EPA, 1985)
Ermans, A.M., F. Delange, M. Van der Velden and J. Klnthaert. 1972.
Possible role of cyanide and thlocyanate in the etiology of endemic
cretinism. Adv. Exp. Med. B1ol. 30: 455-486. (CHed 1n U.S. EPA, 1985)
-23-
-------
Federal Register. 1984. Environmental Protection Agency. Proposed guide-
lines for carcinogenic risk assessment. 49 FR 46294-46299.
Foulds, W.S., J.S. Cant, I.A. Chlsholm, J. Bronte-Stewart and J. WHson.
1968. Hydroxocobalamln 1n the treatment of Leber's hereditary optic
atrophy. Lancet. (Great Britain). 1: 896-897. (Cited In U.S. EPA, 1985)
Frledberg, K.D. and H.A. Schwarzkopf. 1969. Blausaureexhalatlon be1 der
cyanldverglftung (The exhalation of hydrocyanic add 1n cyanide poisoning)
Arch. Toxlcol. 24: 235-248. (Cited 1n U.S. EPA, 1985)
Gettler, A.O. and 0.0. Balne. 1938. The toxicology of cyanide. Am. J.
Med. Sci. 195: 182-198. (Cited In U.S. EPA, 1985)
Graedel, T.E. 1978. Chemical Compounds 1n the Atmosphere. Academic Press,
NY. p. 282-286.
Hansch, C. and A-J. Leo. 1979. SubstHuent Constants for Correlation
Analysis 1n Chemistry and Biology. John WHey and Sons, Inc. NY. p. 172.
Hardy, H.L. W.M. Jeffries, M.M. Wesserman and W.R. Waddell. 1950. Th1o-
cyanate effect following Industrial cyanide exposure—report of two cases.
N. Engl. J. Med. 242: 968-972. (Cited 1n U.S. EPA, 1985)
Hayes, W.T., Jr. 1967. The 90-dose LD5Q and a chronlcHy factor as
measures of toxldty. Toxlcol. Appl. Pharmacol. 11: 327-335. (Cited 1n
U.S. EPA, 1985)
-24-
-------
Hertting, G., 0. Kraupp, E. Schnetz and S. Wleketlch. 1960. Untersuchungen
uber die Folgen elner chronlschen Verabrelchung akut toxlscher Dosen von
Natrium cyanld an Hunden. Acta Pharmacol. Toxlcol. 17: 27-43. (Ger.)
(Cited 1n U.S. EPA, 1985}
Howard, J.W. and R.F. Hanzal. 1955. Chronic toxldty for rats of food
treated with hydrogen cyanide. J. Agrlc. Food Chem. 3: 325-329. (Cited 1n
U.S. EPA, 1985)
Hugod, C. 1981. Myocardlal morphology 1n rabbits exposed to various gas-
phase constituents of tobacco smoke - an ultrastructural study. Athero-
sclerosis (Shannon, Ireland). 4(2): 181-190. (Cited In U.S. EPA, 1985)
Karube, I., T. Matsunaga, T. Nakahara, S. Suzuki and T. Kada. 1981. Preli-
minary screening of mutagens. with a mlcroblal sensor. Anal. Chem. 53(7):
1024-1026. (Cited 1n U.S. EPA, 1985)
Kushl, A., T. Matsumoto and D. Yoshlda. 1983. Mutagen from the gaseous
phase of protein pyrolyzate. Agrlc. B1ol. Chem. 47(9): 1979-1982. (Cited
In U.S. EPA, 1985)
Leo, A., C. Hansch and D.A. Elklns. 1971. Partition coefficients and their
uses. Chem. Rev. 6: 525-616.
MacKenzle, A.D. and C.I. Phillips. 1968. West Indian amblyopla. Brain
(Great Britain). 91: 249-260. (Cited 1n U.S. EPA, 1985)
-25-
-------
Makene, W.J. and J. Wilson. 1972. Biochemical studies 1n Tanzanlan
patients with ataxlc tropical neuropathy. J. Neurol. Neurosurg. Psychiatry
(Great Britain). 35: 31-35. (Cited In U.S. EPA, 1985)
Monekosso, G.L. and J. Wilson. 1966. Plasma thlocyanate and vitamin B,_
In Nigerian patients with degenerative neurological disease. Lancet (Great
Britain). 1: 1062-1064. (Cited In U.S. EPA, 1985)
Mushett, C.W., K.L. Kelley, G.E. Boxer and J.C. Rlckards. 1952. Antidotal
efficacy of vitamin B,? (hydroxo-cobalamln) 1n experimental cyanide
poisoning. Proc. Soc. Exp. Biol. Med. 81: 234-237. (Cited In U.S. EPA,
1985)
Nlchplls, P. 1975. The effect of sulflde on cytochrome aa«. IsosteMc
and allosterlc shifts of the reduced peak. Blochem. Blophys. Acta. 396:
24-35. (Cited In U.S. EPA, 1985)
NIOSH (National Institute for Occupational Safety and Health). 1976.
Criteria for a Recommended Standard...Occupational Exposure to Hydrogen
Cyanide and Cyanide Salts (NaCN, KCN and Ca(CN)2). U.S. DHEW. U.S. GPO,
Washington, DC. NIOSH Publ. No. 77-108. (Cited In U.S. EPA, 1985)
OSHA (Occupational Safety and Health Administration). 1981. General
Industry OSHA Safety and Health Standards (29 CFR 1910). U.S. Dept. Labor.
OSHA 2206, Washington, DC. p. 633. (Cited In U.S. EPA, 1985)
-26-
-------
Osuntokun, B.O. 1968. An ataxlc neuropathy 1n Nigeria. Brain. 91:
215-248. (Cited in U.S. EPA, 1985)
Osuntokun, B.O. 1972. Chronic cyanide neurotoxldty and neuropathy 1n
Nigerians. Plant Foods Hum. Nutr. (Great Britain). 2: 215-266. (Cited 1n
U.S. EPA, 1985)
Osuntokun, B.O., F.L. Monekosso and J. Wilson. 1969. Relationship of a
degenerative tropical neuropathy to diet, report of a field study. Br. Med.
J. (Great Britain). 1: 547-550. (Cited In U.S. EPA, 1985)
Osuntokun, B.O., A. Aladetoylnbo and A.O.G. Adeuja. 1970. Free-cyanide
levels 1n tropical atoxic neuropathy. Lancet (Great Britain). 2: 372-373.
(Cited 1n U.S. EPA, 1985)
Palmer, I.S. and O.E. Olson. 1979. Partial prevention by cyanide of sele-
nium poisoning 1n rats. Blochem. Blophys. Res. Commun. 90(4): 1379-1386.
(Cited 1n U.S. EPA, 1985)
Pettlgrew, A.R. and G.S. Fell. 1972. Simplified coloMmetMc determination
of thlocyanate 1n biological fluid and Us application to Investigation of
toxic amblyoplas. Clln. Chem. 18: 996-1000. (Cited 1n U.S. EPA, 1985)
Pettlgrew, A.R. and G.S. Fell. 1973. M1crod1ffus1on method for estimation
of cyanide in whole blood and Us application to the study of conversion of
cyanide to thlocyanate. Clin. Chem. 19: 466-471. (Cited In U.S. EPA, 1985)
-27-
-------
PhllbMck, D.J., J.B. Hopkins, O.C. Hill, J.C. Alexander and R.G. Thomson.
1979. Effect of prolonged cyanide and thlocyanate feeding 1n rats. J.
Toxlcol. Environ. Health. 5: 579-592. (Cited In U.S. EPA, 1985)
Sandberg, C.G. 1967. A case of chronic poisoning with potassium cyanide.
Acta Med. Scand. 181: 233-236. (Cited In U.S. EPA, 1985)
Smith, L., H. Kruszyna and R.P. Smith. 1977. The effect of methemoglobln
on the Inhibition of cytochrome c oxldase by cyanide, sulflde or azlde.
Blochem. Pharmacol. 26: 2247-2250. (Cited 1n U.S. EPA, 1985)
Smith, R.P. and M.V. Olson. 1973. Drug-Induced methemogloblnemla. Semin.
Hematol. 10: 253-268. (Cited In U.S. EPA, 1985)
Tewe, 0.0. 1982. Effect of dietary cyanide on the performance, metabolism
and pathology of the African rat (Crlcetomys gamblanus Waterhouse). Nutr.
Rep. Int. 26(4): 529-536. (Cited 1n U.S. EPA, 1985)
Tewe, 0.0. and J.H. Maner. 1980. Cyanide, protein and Iodine Interactions
1n the performance, metabolism and pathology of pigs. Res. Vet. Sd.
29(3): 271-276. (Cited In U.S. EPA, 1985)
Tewe, 0.0. and J.H. Maner. 1981a. Long-term and carry-over effect of
dietary 1nogran1c cyanide (KCN) 1n the life cycle performance and metabolism
of rats. Toxlcol. Appl. Pharmacol. 58(1): 1-7. (Cited 1n U.S. EPA, 1985)
-28-
-------
Tewe, 0.0. and J.H. Maner. 19815. Performance and pathophyslologlcal
changes 1n pregnant pigs fed cassava diets containing different levels of
cyanide. Res. Vet. Sc1. 30(2): 147-151. (Cited In U.S. EPA, 1985)
Tewe, 0.0. and J.H. Maner. 1982. Cyanide, protein and Iodine Interaction
1n the physiology and metabolism of rats. Food Chem. 9(3): 195-204.
(Cited 1n U.S. EPA, 1985)
Towlll, I.E., J.S. Drury, B.L. WhHMeld, E.B. Lewis, E.L. Galyan and A.S.
Mammons. 1978. Reviews of the Environmental Effects of Pollutants. V.
Cyanide. U.S. EPA, HERL, ORD, Cincinnati, OH. EPA-600/1-78-027. NTIS PB
289920.
U.S. EPA. 1980a. Ambient Water Quality Criteria for Cyanides, with Errata
for Ambient- Water Quality Criteria Documents dated June 9, 1981 (Updated:
February 23, 1982). Prepared by the Environmental Criteria and Assessment
Office, Cincinnati, OH, OHEA for the Office of Water Regulations and Stan-
dards, Criteria and Standards Division, Washington, DC. EPA 440/5-80-035.
NTIS PB 81-117483.
U.S. EPA. 1980b. Guidelines and Methodology Used 1n the Preparation of
Health Effects Assessment Chapters of the Consent Decree Water Quality
Criteria. Federal Register. 45: 79347-79357.
U.S. EPA. 1983. Methodology and Guidelines for Reportable Quantity Deter-
minations Based on Chronic Tox1c1ty Data. Prepared by the Environmental
Criteria and Assessment Office, Cincinnati, OH, OHEA for the Office of Solid
Waste and Emergency Response, Washington, DC.
-29-
-------
U.S. EPA. 1985. Drinking Water Criteria Document for Cyanide. Prepared by
the Environmental Criteria and Assessment Office, Cincinnati, OH, OHEA for
the Office of Drinking Water, Washington, DC. Final draft.
U.S. Public Health Service. 1962. Drinking Water Standards. U.S. Gov.
Printing Off., Washington, D.C. PHS Publ. No. 956. (Cited in U.S. EPA,
1985)
VeHh, G.D., D.L. DeFoe and B.V. Bergstedt. 1979. Measuring and estimating
the bloconcentratlon factor of chemicals 1n fish. J. Fish Res. Board Can.
36: 1040-1048.
Way, J.L. 1981. Pharmacologlc aspects of cyanide and Its antagonism. lr\_:
Cyanide Biology, B. Vennesland, E.E. Conn and C. Knowles, Ed. Academic,
London, England, p. 29-49. (Cited 1n U.S. EPA, 1985)
Weast, R.C., Ed. 1980. CRC Handbook of Chemistry and Physics, 61st ed.
CRC Press, Boca Raton, FL. p. B-98, B-133, B-147.
Wilson, J. 1983. Cyanide In human disease: A review of clinical and
laboratory evidence. Fundam. Appl. Toxlcol. 3(5): 397-399. (Cited 1n U.S.
EPA, 1985)
Wilson, J. and D.M. Matthews. 1966. Metabolic Interrelationships between
cyanide, thlocyanate and vitamin B,,, in smokers and non smokers. Clin.
Sci. 31: 1-7. (Cited 1n U.S. EPA, 1985)
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-------
Wokes, F. 1958. Tobacco amblyopla. Lancet. 2: 526-527. (Cited 1n U.S.
EPA, 1985)
Yamamoto, K., Y. Yamamoto, H. Hatlorl and T. Samori. 1982. Effects of
routes of administration on the cyanide concentration distribution In the
various organs of cyanide Intoxicated rats. Tohoku J. Exp. Med. 137(1):
73-78. (Cited In U.S. EPA, 1985)
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APPENDIX
Summary Table for Sodium Cyanide
CO
ro
I
Inhalation
AIS
AIC
Oral
AIS
AIC
Species Experimental Effect
Dose/Exposure
NA NA NA
NA NA NA
rat NOEL - 10.8 mg NA
CN-/kg/day
Acceptable Intake Reference
(AIS or AIC)
NA NA
ND
ND NA
2.8 NaCN Howard and
mg/day Hanzal, 1955;
Maximum
composite
score
dog
6 mg/kg bw/day
for 15 months
(RVd=1.9)
degeneration of
ganglion cells
In CNS (RVe=6)
11.4
U.S. EPA, 1985
Herttlng
et al.. 1960
NA = Not applicable; ND = not derived
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