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
... 1
... 3
... 3
... 3
... 4
... 4
... 4
... 7
... 8
... 8
. . . . 11
... 11
. . . . 11
... 11
... 11
... 13
... 13
... 13
... 13
... 13
... 13
... 13
... 13
... 14
... 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.
                                      -1-

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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.
                                      -2-

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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.
                                      -3-

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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
                                      -4-

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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).
                                      -7-

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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.
                                      -8-

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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
                                     -11-

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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-

-------
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-

-------
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-

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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)

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                                     -23-

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                                     -24-

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                                     -25-

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                                     -28-

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                                     -29-

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                                     -30-

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                                    -31-

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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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