v>EPA
                Ur.itecl States
                Environmental Protection
                Agency
                Office of Water
                Regulations and Standards
                Criteria and Standards Division
                Washington DC 20460
EPA 440/5-80-037
October 1980
Ambient
Water Quality
Criteria for
Cyanides

-------
      AMBIENT WATER QUALITY CRITERIA FOR

                  CYANIDE
                 Prepared By
    U.S. ENVIRONMENTAL PROTECTION AGENCY

  Office of Water Regulations and Standards
       Criteria and Standards Division
              Washington, D.C.

    Office of Research and Development
Environmental Criteria and Assessment Office
              Cincinnati, Ohio

        Carcinogen Assessment Group
             Washington,  D.C.

    Environmental Research Laboratories
             Corvalis, Oregon
             Duluth,  Minnesota
           Gulf Breeze, Florida
        Narragansett, Rhode Island

-------
                              DISCLAIMER
     This  report  has  been reviewed by the  Environmental  Criteria and
Assessment Office, U.S.  Environmental  Protection  Agency,  and approved
for publication.   Mention of trade names or commercial products does not
constitute endorsement or recommendation for use.
                         AVAILABILITY  NOTICE
      This  document  is available to  the public through  the  National
Technical Information Service, (NTIS), Springfield, Virginia  22161.

-------
                               FOREWORD

    Section 304  (a)(l)  of  the Clean Water Act  of  1977 (P.L.  95-217),
requires the Administrator  of the Environmental Protection Agency to
publish criteria  for water  quality  accurately reflecting  the  latest
scientific knowledge on  the  kind  and extent of all identifiable effects
on  health  and  welfare  which  may be  expected from  the presence  of
pollutants in  any body of water, including ground water.  Proposed water
quality criteria  for the 65  toxic  pollutants  listed  under section 307
(a)(l) of  the  Clean Water  Act  were  developed  and  a notice  of  their
availability was published for public comment on March 15, 1979 (44 FR
15926), July 25, 1979 (44  FR 43660), and October 1, 1979 (44 FR 56628).
This document  is  a  revision  of  those  proposed criteria  based  upon a
consideration of  comments received from  other  Federal  Agencies,  State
agencies,   special  interest  groups,  and  individual  scientists.    The
criteria contained in this document replace any previously published EPA
criteria for  the  65 pollutants.   This  criterion  document  is  also
published  in satisifaction of paragraph 11 of the Settlement Agreement
in  Natural  Resources Defense Counci 1, et.  a!..  vs. Train,  8  ERC 2120
(D.D.C. 1976), modified, 12 ERC 1833 (D.D.C.  1979).

    The term "water  quality criteria"  is used  in  two  sections  of the
Clean Water Act, section 304  (a)(l)  and section 303 (c)(2).  The term has
a different program  impact  in  each section.   In section 304,  the term
represents a non-regulatory,  scientific  assessment of  ecological  ef-
fects. The criteria  presented  in  this  publication  are such  scientific
assessments.   Such  water  quality criteria  associated with  specific
stream uses when adopted as  State water quality  standards under section
303  become  enforceable  maximum  acceptable  levels of  a  pollutant  in
ambient waters.  The water quality criteria adopted in the State water
quality standards could have the same numerical limits as the  criteria
developed  under section  304.  However, in many situations States may want
to adjust  water quality  criteria  developed under section 304 to reflect
local  environmental  conditions  and  human  exposure  patterns  before
incorporation   into  water quality  standards.    It  is  not until  their
adoption as part of the  State water quality standards that the  criteria
become regulatory.

    Guidelines  to assist the  States  in  the modification of  criteria
presented   in   this   document,  in  the  development  of  water  quality
standards,  and  in  other water-related programs of this Agency, are being
developed  by EPA.
                                    STEVEN SCHATZOW
                                    Deputy Assistant Administrator
                                    Office of Water Regulations and Standards
                                   111

-------
                                 ACKNOWLEDGEMENT


Aquatic Life Toxicology:

   Charles E. Stephan ,  ERL-Duluth            John H. Gentile, ERL-Narragansett
   U.S.  Environmental  Protection  Agency      U.S. Environmental Protection Agency

Mammalian Toxicology and Human Health Effects:

   Roger Smith (author)                      Robert M. Bruce, ECAO-RTP
   Dartmouth Medical College                 U.S. Environmental Protection Agency

   Steven D. Lutkenhoff (doc. mgr.)          Edward Calabrese
   ECAO-Cin                                  University of Massachusetts
   U.S. Environmental Protection Agency

   J.F. Stara, ECAO-Cin, (doc. mgr.)         Patrick Durkin
   U.S. Environmental Protection Agency      Syracuse Research Corporation

   David Fankhauser                          Vincent Finelli
   University of Cincinnati                  University of Cincinnati

   Ernest Foulkes                            A.N. Milbert
   University of Cincinnati                  National Institute for Occupational
                                                Safety and Health

   Havish Sikka
   Syracuse Research Corporation


Technical Support Services Staff:  D.J. Reisman, M.A. Garlough, B.L. Zwayer,
P.A. Daunt, K.S. Edwards,  T.A. Scandura, A.T. Pressley, C.A. Cooper,
M.M. Denessen.

Clerical Staff:  C.A. Haynes, S.J.  Faehr, L.A. Wade, D. Jones, B.J. Bordicks,
B.J. Quesnell, T. Highland, B. Gardiner.
                                          IV

-------
                           TABLE OF CONTENTS
Criteria Summary

Introduction                                                A-l

Aquatic Life Toxicology                                     B-l
     Introduction                                           B-l
     Effects                                                B-3
          Acute Toxicity                                    B-3
          Chronic Toxicity                                  B-4
          Plant Effects                                     B-5
          Residues                                          B-5
          Miscellaneous                                     B-5
          Summary                                           B-6
     Criteria                                               B-7
     References                                             B-28

Mammalian Toxicology and Human Health Effects               C-l
     Introduction                                           C-l
     Exposure                                               C-2
          Ingestion from Water                              C-4
          Ingestion from Food                               C-5
          Inhalation                                        C-7
          Dermal                                            C-8
     Pharmacokinetics                                       C-8
          Absorption                                        C-8
          Distribution                                      C-9
          Metabolism                                        C-10
          Excretion                                         C-14
     Effects                                                C-14
          Acute, Subacute, and Chronic Toxicity             C-14
          Synergism and/or Antagonism                       C-20
          Teratogenicity, Mutagenicity, and Carcinogenicity C-22
     Criterion Formulation                                  C-24
          Existing Guidelines and Standards                 C-24
          Special Groups at Risk                            C-25
          Basis and Derivation of Criteria                  C-25
     References                                             C-29

-------
                               CRITERIA  DOCUMENT
                                    CYANIDE

CRITERIA
                                 Aquatic Life
    For free  cyanide  (sum  of cyanide present as  HCN and CN~,  expressed  as
CN) the criterion  to  protect  freshwater  aquatic  life  as derived  using  the
Guidelines  is  3.5  ug/1  as  a  24-hour  average,  and the  concentration  should
not exceed 52 wg/1  at any time.
    The available  data for free cyanide  (sum of cyanide present  as  HCN  and
CN~,  expressed  as  CN)  indicate  that  acute toxicity  to saltwater  aquatic
life  occurs  at  concentrations as  low as 30 ug/1  and  would occur at  lower
concentrations among species  that  are more  sensitive than those  tested.   If
the  acute-chronic  ratio  for  saltwater organisms  is  similar  to that  for
freshwater  organisms,  chronic toxicity would occur at  concentrations  as  low
as 2.0 yg/1 for the  tested  species  and  at lower  concentrations among  species
that are more sensitive than those tested.

                                 Human Health
    The ambient  water quality criterion for  cyanide  is  recommended to  be
identical  to the existing water standard which is  200 ug/1.   Analysis  of  the
toxic  effects  data  resulted  in a  calculated level  which  is  protective  of
human  health  against  the  ingestion of contaminated  water  and contaminated
aquatic organisms.   The  calculated  value is comparable  to the present  stan-
dard.  For  this reason a selective  criterion based  on   exposure  solely  from
consumption of 6.5  grams  of aquatic organisms was not  derived.
                                     VI

-------
                                  INTRODUCTION
     Cyanides  are  defined  as  organic or inorganic compounds which contain the
-CN  group.   Hydrogen cyanide  (HCN)  is lighter  than  air and diffuses rapid-
ly.   Free  HCN is very reactive  and  occurs  only rarely  in  nature;  it  is us-
ually prepared commercially  from ammonia  and methane  at  elevated tempera-
tures with  a  platinum catalyst.   Hydrogen cyanide  is  soluble  in all propor-
tions  in water.  It  is  quite  volatile, having  a vapor  pressure of 100 torr
at -178'C;  360 torr  at  7*C;  658.7  torr  at 21.9'C;  and 760 torr  at  26.7*C
(boiling point)  (Towill, et al.  1978).  Cyanide ions  form complexes  with a
variety  of  metals,  especially  those of the  transition series.    Ferricyanides
and  ferrocyanides  have  a variety of  industrial  uses  but do not release cya-
nide  unless exposed to ultraviolet  light.   Thus,  sunlight can  lead  to the
mobilization  of  cyanide  in  waters   containing   iron  cyanides.   Cyanogen
[(CNL]  is  a flammable  gas  of high  toxicity  which has a  vapor pressure of
about 5  atm.  at  20°C  (Towill,  et al. 1978).  It reacts  slowly  with water to
produce  HCN,  cyanic  acid,  and other  compounds.   Cyanates contain  the  -OCN
radical.  Inorganic cyanates,  which  are formed  industrially by  the oxidation
of cyanide  salts,  hydrolyze  in  water  to  form ammonia  and bicarbonate  ion.
Alkyl  cyanates  trimerize readily (when  sufficiently  concentrated) to  form
cyanurates.   Alkyl  isocyanates contain the  -NCO radical and are formed  from
cyanates;  they,  too, are  readily  hydrolyzed.   Thiocyanates (-SCN  radical)
are formed  from cyanides and sulfur-containing  materials and are more  stable
than  cyanates.   Solutions  of  thiocyanates  form free  hydrogen  cyanide  in  a-
cidic media.  Nitriles are  organic  compounds that  have  a  cyanide group  as a
substituent.  The nitriles are generally  much  less  toxic  than   the  free hy-
drogen  cyanide  or  the  metal   cyanides.   Cyanohydrins  [R,,C(QH)CN]  are  toxic
compounds which  can  decompose with  the  release  of  HCN   or CN~  under  en-
vironmental  conditions (U.S.  EPA, 1979).

                                      A-l

-------
                                  REFERENCES

Towill, I.E., et al.   1978.   Reviews  of the environmental effects  of  pollu-
tants.  V. Cyanide.  U.S. EPA.  NTIS-PB 289-920.   p.  11.

U.S.  EPA.   1979.   Water-related environmental  fate  of  129  priority  pollu-
tants.  Vol. I.   EPA 440/4-79-029a.
                                      A-2

-------
Aquatic Life Toxicology*
                                 INTRODUCTION
     Compounds containing the  cyanide  group  (CN)  are used and readily formed
in  many  industrial processes  and  can  be  found  in  a variety  of  effluents,
such as  those from the  steel, petroleum,  plastics,  synthetic  fibers,  metal
plating, mining,  and  chemical  industries.   Cyanide commonly  occurs  in  water
as  hydrocyanic  acid  (HCN),  the cyanide ion  (CN~),  simple  cyanides,  roetal-
locyanide complexes,  or  as  simple  chain and complex  ring organic  compounds.
"Free  cyanide"  is defined as  the  sum of  the  cyanide present  as  HCN  and as
CN~.   The   alkali  metal   salts such  as potassium  cyanide  (KCN)  and  sodium
cyanide (NaCN) are  very  soluble in aqueous solutions and  the resulting  cya-
nide ions readily hydrolyze  with water to form HCN.  The extent of HCN  for-
mation  is  mainly  dependent  upon water  temperature and  pH.   At 20°C and  a
pH of  8 or  below the fraction  of  free cyanide existing  as  HCN is  at  least
0.96.
     The cyanide  ion  (CN~)  can  combine  with  various  heavy metal ions  to
form metallocyanide  complex  anions,  whose  stability  is  highly  variable.
Zinc and  cadmium cyanide complexes,  when  diluted  with water,  are  known  to
dissociate   rapidly  and  nearly  completely  to form  HCN.  Some  of   the other
metallocyanide anions, such  as those  formed with copper, nickel,   and  iron,
demonstrate  varying  degrees   of  stability.    The  hexacyanoferrate(II)   and
-(III)  complexes  are subject  to  direct  photolysis  by  natural light.   The
*The reader is referred to the Guidelines  for  Deriving  Water  Quality Criter-
ia for the Protection of Aquatic  Life and  Its  Uses in order to  better under-
stand  the following  discussion  and  recommendation.   The  following  tables
contain the appropriate data  that  were  found  in  the literature,  and  at  the
bottom of each table  are  calculations for deriving  various measures  of  tox-
icity as described in the  Guidelines.
                                     B-l

-------
release  of cyanide  ion by  this phenomenon  may be  important  in relatively
clear receiving waters.
     The  toxicity  to aquatic organisms of most  simple  cyanides  and metallo-
cyanide complexes  is due mostly  to  the  presence  of HCN  as derived from ioni-
zation, dissociation,  and  photodecomposition of cyanide-containing compounds
(Doudoroff,  et al.  1966;   Smith,  et  al.  1979),  although  the   cyanide  ion
(CN~)  is  also  toxic (Broderius, et  al.  1977).   In  most cases  the  complex
ions themselves  have relatively low  toxicity.   The  available  literature on
the  toxicity  to fish  of cyanides  and  related compounds was  critically  re-
viewed by Doudoroff  (1976).
     Since  both  HCN and CN~ are toxic  to  aquatic  life and since the vast
majority of free cyanide usually exists as the more  toxic HCN,  and since  al-
most all  existing  CN~ can  be  readily converted  to HCN  at pH  values that
commonly  exist  in  surface  waters,  the  cyanide  criterion  will  be  stated in
terms of free cyanide  expressed  as  CN.  Free cyanide is a much more reliable
index of  toxicity  than total cyanide since  total  cyanide could  include  ni-
triles   (organic  cyanides)   and  stable metallocyanide complexes.    In  highly
alkaline waters a  free cyanide criterion based  on the  relative  toxicity of
HCN  and  the CN~  ion may be  appropriate  due to  the dependence  of the form
of free cyanide on pH.
     All  of the cyanide  concentrations given  herein  are  free   cyanide  ex-
pressed as CN.  Data reported in the original literature  as  ug of HCN/1 were
adjusted to free cyanide as CN as follows:
(ug of  Free Cyanide as  CN/1) =  (yg  of HCN/1) (1  + IQPH-pKHCN)   x  mol.  wt. CN
                                                                    mol. wt.  HCN
                                     B-2

-------
                3 i-3440  *   2347.2      (izatt, et al. 1962)
                           T + 273.16
where T » degrees Celsius.

                                    EFFECTS
Acute Toxicity
    The results  of  7 acute tests with  6  freshwater invertebrate species are
given in  Table  1.   With three exceptions  (Oseid  and Smith,  1979;  U.S.  EPA,
1980a),  results are  based  on static  tests with  unmeasured concentrations.
Most  of  the  species  tested  were  considerably more  tolerant  than  fishes.
Daphnia  pulex  and  Gammarus   pseudolimnaeus,   however,  were comparable  to
fishes  in sensitivity.   There  was  greater  variability  in  sensitivity  of
invertebrate species to free cyanide than was observed for fish species.
    The  96-hour LC5Q  values  based on acute  toxicity  tests  with  10  fish
species are summarized  in Table  1.  The  greatest  number of  tests  were  con-
ducted with brook trout,  bluegill,  and  fathead  minnows.   About 80 percent of
the data  resulted  from studies  conducted  by Smith, et  al.   (1978)  and  Bro-
derius, et al.  (1977).  All of their tests  were conducted using flow-through
techniques  with  the  reported  HCN   levels  calculated   from  analytically
measured free cyanide concentrations.
    Certain life stages and species  of  fishes appear to  be more sensitive to
cyanide than others.   Embryos,  sac fry,  and  warmwater species  tended to  be
the most  resistant.  A review  of pertinent  data  for juvenile  fishes  indi-
cates that  free cyanide  concentrations in the  range  from  about  50 to  200
ug/1  have eventually proven fatal  to most of  the more sensitive  fish  spe-
cies,  with concentrations  much above 200  yg/1  being  rapidly fatal  to  most
fish species.   Thus there is a relatively narrow range of species sensitivi-
ty for fish.   A comparison of acute  toxicity results for  fishes  supports the

                                     B-3

-------
hypothesis  that the  toxicity of simple cyanide  solutions  is underestimated
by static tests, especially  when the cyanide concentrations in the test sol-
utions are not measured.
    A  number of  authors have  reported an  increase  in toxicity  of cyanide
with  reduction  in  dissolved oxygen below  the saturation  level  (Doudoroff,
1976;  Smith, et  al.  1978).   The tolerance  of  fishes to  cyanide  solutions
that are rapidly lethal  has  been observed  to decrease  with  a rise of temper-
ature.   Long-term  lethality tests,  however,  have  demonstrated that juvenile
fishes  are  more  susceptible  to  cyanide  with  a  reduction  in  temperature
(Smith,  et  al.  1978).  No pronounced relationship  has  been observed between
the  acute  toxicity  of  cyanide  to fishes  and alkalinity,  hardness,  or  pH
below about 8.3.
    Based on  Species  Mean Acute  Values  summarized  in  Table  3, the Freshwater
Final Acute  Value,  derived using the calculation  procedures described  in the
Guidelines,  is 52 pg/1.
    For  saltwater  species,  acute toxicity  data  are available for  three in-
vertebrate and  one  fish species  and range from 30 to 372   ug/1-   These few
values suggest  that free cyanide  is  very toxic to saltwater  species,  which
have about the same sensitivity as freshwater organisms.
Chronic Toxicity
    The long-term survival and growth of various  freshwater fish  species was
observed to be  seriously reduced at free cyanide concentrations of  about  20
to 50  vg/1  (Kimball,  et al.  1978;  Koenst,  et al. 1977) (Table 5).  Results
from only a  few full  and partial  life  cycle chronic  tests  with fishes  have
been reported  (Table  2).  Based on reduced  long-term survival  in  an  early
life stage test with  bluegills  and  reduced  reproduction  by brook  trout and
fathead  minnows  in a  partial  life  cycle  and life cycle  test,  the chronic
values were 14,  7.9, and 16  pg/1, respectively.
                                     8-4

-------
     Two freshwater  invertebrate  life cycle tests  (Table  2) were  conducted;
 one with  the  isopod, Asellus communis, and the other with the scud,  Gammarus
 pseudolimnaeus.   The chronic values were  34  and 18  yg/1, respectively.
     The Final  Acute-Chronic Ratio of 14.8 is  the  geometric  mean of  the  five
 acute-chronic  ratios (Table 3).   The Freshwater Final Acute Value  of 52  yg/1
 divided by the Final Acute-Chronic  Ratio of  14.8  results  in  the  Freshwater
 Final  Chronic  Value  for  free cyanide  (expressed as  CN) of 3.5 ug/1  (Table 3).
     No chronic data  are  available for  cyanide  and any saltwater  species.
 Plant  Effects
     Data  on the  toxicity of  free  cyanide  to one  freshwater and  two salt-
 water  species  of algae  are  presented  in  Table 4.  Apparently algae are not
 very sensitive to cyanide  when  compared  with other aquatic  organisms,  and
 adverse  effects  of cyanide  on plants  are unlikely  at concentrations protec-
 tive of acute  effects on most freshwater and  saltwater invertebrate  and fish
 species.
 Residues
     No  residue data were found for cyanide.
 Miscellaneous
    Table  5  contains no data  that  would alter the selection of 3.5 yg/1 as
 the  Final  Chronic Value.   In  fact,  there   are  some  pertinent   additional
 studies,  on  physiological  and behavioral  responses of fishes to  low levels
 of free cyanide, that are supportive of the calculated chronic value.
    Several  authors   (Neil,   1957;  Broderius,  1970;  Dixon,  1975;  Lesniak,
 1977;  Leduc, 1978; Oseid and  Smith,  1979; Rudy, et  al.  1979)  reported  ad-
 verse  effects  due to  cyanide  at  concentrations  as  low  as 10  yg/1.   In
 another study,  Kimball,  et  al. (1978)  reported that no  reproduction occurred
 among  adult bluegills when  exposed  for 289  days  to the  lowest  concentration
tested  (5.2  yg of HCN/1 =  5.4  yg  of free  cyanide as  CN/1).   During  this

                                     B-5

-------
period, however,  only a total  of  13 spawnings occurred in two  controls  and
no dose-response relationship was observed.  Because of  reservations  regard-
ing  the  spawning data,  the chronic  value  for bluegills  was  based  on  long
term fry  survival.   On  the other hand,  the most  sensitive  adverse  effect
caused by cyanide on  both  fathead minnows  and  brook  trout  was  reduced repro-
duction.   The freshwater Final  Chronic  Value of  3.5 ug/1,  based on fish  and
invertebrate  chronic  data,  appears  to be  supported  by these  miscellaneous
studies.
Summary
    All concentrations  herein for free cyanide  (sum  of cyanide  present  as
HCN  and CN~)  are expressed  as  CN.   The data used in  deriving  the criterion
are  predominantly from  flow-through  tests  in  which toxicant  concentrations
were measured.
    Data  on  the  acute  toxicity of  free cyanide  are  available  for   a  wide
variety of freshwater organisms that  are  involved  in diverse community func-
tions.  Except  for  the  more sensitive  invertebrate species, such  as  Daphnia
pulex  and Gammartis  pseudolimnaeus,   invertebrate  species  are  usually  more
tolerant  of cyanide  than are freshwater fish species, which have  most acute
values clustered between 50  to  200 ug/1.   A long-term survival  and two  life
cycle  tests  with  fish  gave  chronic  values  of  7.9,   14,  and  16  ug/1,
respectively.    Chronic  data  for  the  freshwater  invertebrate   species  were
more  variable,  with  Gammarus  pseudolimnaeus being  comparable  to fishes  in
sensitivity and isopods being considerably more tolerant.
    The acute toxicity  of  free cyanide to  saltwater organisms  is  comparable
to that observed for freshwater organisms,  but  no  data are available  con-
cerning chronic  toxicity.   For saltwater aauatic life no  criterion for  free
cyanide can be derived using the Guidelines.
                                      B-6

-------
    Plants  are much more  resistant to  cyanide than animals  and thus their
well-being  is  assured if more sensitive aquatic animals are protected.
                                   CRITERIA
    For  free cyanide (sum  of cyanide present  as  HCN and  CN~,  expressed as
CN) the  criterion to protect  freshwater aquatic  life  as  derived  using the
Guidelines  is  3.5 pg/1  as  a 24-hour  average,  and  the  concentration should
not exceed  52  wg/l at any time.
    The  available  data  for free  cyanide  (sum of cyanide  present as HCN and
CN~  expressed   as  CN)  indicate  that  acute  toxicity  to  saltwater  aquatic
life occurs at concentrations  as  low as  30  ^g/1  and  would occur  at lower
concentrations   among species  more  sensitive  than  those  tested.    If  the
acute-chronic  ratio  for saltwater  organisms  is similar  to that  for fresh-
water organisms,  chronic toxicity  would  occur  at  concentrations as  low as
2.0 yg/1  for the tested  species  and at  lower  concentrations  among species
that are more sensitive  than those tested.
                                     B-7

-------
                            Table 1.  Acute values for cyanide
Species
Method*
LC50/EC50
(UQ/D
Species Mean
Acute Value
(Uq/l)
FRESHWATER SPECIES
Snail,
Physa heterostropha
Snal 1,
Physa heterostropha
Cladoceran,
Daphnla pulex
Isopod,
Ase 1 1 us conmun 1 s
Scud,
Gamnarus pseudo 1 1 mnaeus
Midge,
Tanytarsus dlssimllls
Brook trout (sac fry),
Salvellnus fontlnalls
Brook trout (sac fry),
Salvellnus fontlnalls
Brook trout (sac fry),
Salvellnus fontlnalls
Brook trout (sac fry),
Salvellnus fontlnalls
Brook trout (swim-up fry),
Salvetlnus fontlnalls
Brook trout (swim-up fry),
Salvellnus fontlnalls
Brook trout (swim-up fry),
Salvellnus fontlnalls
Brook trout (swim-up fry).
s.
s,
s,
FT,
FT,
s,
FT.
FT,
FT,
FT,
FT,
FT,
FT,
FT,
U
U
U
M
M
M
H
M
M
M
M
H
M
H
432
431
83
2,326
167
2,240
105
342
507
252
84
54.4
86.5
104
431
83
2,326
167
2,240
Salvellnus fontlnalls
                                                                       Reference
                                                                       Patrick, et a I. 1968
                                                                       Cairns & Scheler,
                                                                       1958

                                                                       Lee,  1976
                                                                       Oseld  & Smith,  1979
                                                                       Oseld 4 Smith,  1979
                                                                       U.S. EPA,  1980a
                                                                       Smith, et al. 1978
                                                                       Smith, et al.  1978
                                                                       Smith, et al.  1978
                                                                       Smith, et al.  1978
                                                                       Smith, et al.  1978
                                                                       Smith, et al.  1978
                                                                       Smith, et al. 1978
                                                                       Smith, et al.  1978
                                                        B-8

-------
Table 1.  (Continued)
                                        LC50/EC50
Species                     Method*      (ug/l)

Brook trout (swim-up fry),  FT, M            90.3
Salvellnus fontlnalls

Brook trout (Juvenile),     FT, M            73.5
Salvellnus tontlnalls

Brook trout (Juvenile),     FT, M            83
Salvellnus fontlnalls

Brook trout (juvenile),     FT, M            75
Salvellnus fontlnalls

Brook trout (Juvenile),     FT, M            86.4
SaIve11nus font Ina11s

Brook trout (juvenile),     FT, M            91.9
Salvellnus fontlnalls

Brook trout (juvenile),     FT, M            99
SaIveI Inus font InaI Is

Brook trout (juvenile),     FT, M            96.7
Salvellnus tontlnalls

Brook trout (juvenile),     FT, M           112
SaIvelInus fontlnalIs

Brook trout (juvenile),     FT, M            52
SalvelInus fontlnalIs

Brook trout (juvenile),     FT, M            60.2
Salvellnus fontlnalls

Brook trout (juvenile),     FT, M            66.8
SalvelInus fontlnalIs

Brook trout (juvenile),     FT, M            71.4
Salvellnus fontlnalls

Brook trout (juvenile),     FT, M            97
Salvellnus fontlnalls
                                                      Species Mean
                                                       Acute Value
                                                                        Reference

                                                                        Smith, et al.  1978
                                                                        Smith, et al.  1978
                                                                        Smith, et al.  1978
                                                                        Smith, et al.  1978
                                                                        Smith, et al.  1978
                                                                        Smith, et al.  1978
                                                                        Smith, et al.  1978
                                                                        Smith, et al.  1978
                                                                        Smith, et al. 1978
                                                                        Smith, et al. 1978
                                                                        Smith, et al. 1978
                                                                        Smith, et al. 1978
                                                                        Smith, et al. 1978
                                                                        Smith, et al. 1978
                                                B-9

-------
Table  1.  (Continued)
Species
Brook trout • (Juvenl le) ,
Salvel Inus fontlnal Is
Brook trout (adult),
Salvel Inus font! nails
Rainbow trout (Juvenile),
Sal mo galrdnerl
Goldfish (juvenile),
Carasslus auratus
Fathead minnow (fry),
Plmephales promelas
Fathead minnow (fry),
Plmephales promelas
Fathead minnow (fry),
Plmephales prome las
Fathead minnow (fry),
Plmephales promelas
Fathead minnow (fry),
Plmephales promelas
Fathead minnow (juvenile),
Plmephales promelas
Fathead minnow (juvenile),
Plmephales promelas
Fathead minnow (juvenile),
Plmephales promelas
Fathead minnow (Juvenile),
Plmephales promelas
Fathead minnow (juvenile),
Plmephales promelas
Method*
FT,
FT.
FT,
FT,
FT,
FT,
FT,
FT,
FT,
FT,
FT,
FT,
FT,
FT,
M
M
M
M
M
M
M
M
M
M
M
M
M
M
Species Mean
LC50/EC50 Acute Value
Cug/l) (wo/1)
143
156 103
57 57
318 318
120
98.7
81.8
110
116
119
126
81.5
124
137
Reference
Smith, et
Cardwel 1,
1976
Smith, et
Cardwel 1,
1976
Smith, et
Smith,
Smith,
Smith,
Smith,
Smith,
Smith,
Smith,
Smith,
Smith,
et
et
et
et
et
et
et
et
et
al
et
al
et
al
al
al
al
al
al
al
al
al
al
. 1978
al.
. 1978
al.
. 1978
. 1978
. 1978
. 1978
. 1978
. 1978
. 1978
. 1978
. 1978
. 1978
                                            B-10

-------
Table t.   (Continued)
Species
Fathead minnow (juveni
Ptmephales promelas
Fathead minnow (Juveni
Plmephales promelas
Fathead minnow (juveni
Plmephales promelas
Fathead minnow (juveni
Plmephales promelas
Fathead minnow (juveni
Plmephales promelas
Fathead minnow (juveni
Plmephales promelas
Fathead minnow (juveni
Plmephales promelas
Fathead minnow (juveni
Plmephales promelas
Fathead minnow (juveni
P 1 mepha 1 es promelas
Fathead minnow (juveni
Plmephales promelas
Fathead minnow (juveni
Plmephales promelas
Fathead minnow (juveni
Plmephales promelas
Fathead minnow (juveni
PI mepha tes promelas
Fathead minnow (juveni
Plmephales promelas
Method*
le),
le),
le),
le).
le).
le),
le).
le),
le).
le).
le),
le).
le).
le).
FT,
FT,
FT,
FT,
FT,
FT,
FT,
FT.
FT,
FT,
s.
FT,
FT.
FT,
M
M
M
M
M
M
M
M
M
M
U
M
M
M
LC50/EC50
(ug/n
131
105
119
131
122
161
188
175
163
169
230
120
113
128
Species Mean
Acute Value
(ug/l) Reference
Smith.
Smith,
Smith,
Smith,
Smith,
Smith,
Smith,
Smith,
Smith,
Smith,
et
et
et
et
et
et
et
et
et
et
Doudorof f
Broderlus
1977
Broderlus
1977
Broderlus
1977
al.
al.
al.
al.
al.
al.
al.
al.
al.
al.
1978
1978
1978
1978
1978
1978
1978
1978
1978
1978
, 1956
. et
, et
, et
al.
al.
al.
                                               B-ll

-------
Table  1.  (Continued)
Species Method*
Fathead minnow (Juvenile), FT, M
Plmephales promelas
Fathead minnow, S, M
Plmephales promelas
Fathead minnow, S, M
Plmephales promelas
Mosqultoflsh, S, U
Gambusla afflnls
Guppy (adult), FT, M
Poec Ilia ret 1 cu 1 ata
Blueglll (fry), FT, M
Lepomls macrochlrus
Blueglll (fry), FT, M
Lepomls macrochlrus
Blueglll (fry), FT, M
Lepomls macrochlrus
Bluegll 1 (fry), FT, M
Lepomls macrochlrus
Blueglll (juvenile), FT, M
Lepomls macrochlrus
Blueglll (juvenile), FT, M
Lepomls macrochlrus
Blueglll (Juvenile), FT, M
Lepomls macrochlrus
Blueglll (juvenile), FT, M
Lepomls macrochlrus
Blueglll (Juvenile), FT, M
Lepomls macrochlrus
Species Mean
LC50/EC50 Acute Value
(u^/l ) (ug/l) Reference
128 - Broderlus, et al.
1977
350 - Henderson, et al.
1961
230 125 Henderson, et al.
1961
639 639 Wat ten, et al.
1957
147 147 Anderson & Weber,
1975
364 - Smith, et al. 1978
232 - Smith, et al. 1978
279 - Smith, et al. 1978
273 - Smith, et al. 1978
81 - Smith, et al. 1978
85.7 - Smith, et al. 1978
74 - Smith, et al. 1978
100 - Smith, et al. 1978
107 - Smith, et al. 1978
                                      B-12

-------
Table I.  (Continued)
                                        LC50/EC50
Species                     Method*      (ug/1)

Blueglll (juvenile),        FT,  M            99
Lepomls macrochlrus

Blueglll (juvenile),        FT,  M           113
Lepomls macrochlrus

Blueglll (Juvenile),        FT,  M           121
Lepomls macrochlrus

Blueglll (juvenile),        FT,  M           126
Lepomls macrochlrus

Blueglll (juvenile),         S,  U           180
Lepomls macrochlrus

Blueglll,                    S,  U           ISO
Lepomls macrochlrus

Bluegill (juvenile),         S,  M           150
Lepomls macrochlrus

Blueglll (juvenile),         S,  M           160
Lepomls macrochlrus

Largemouth boss             FT,  M           102
(juvenlle),
Mlcropterus salmoIdes

Black crapple,              FT,  M           102
Pomoxls nlgromaculntus

Yellow perch (fry),         FT,  M           288
Perca flavescens

Yellow perch (fry),         FT,  M           330
Perca flavescens

Yellow perch (Juvenile),    FT,  M            88.9
Perca flavescens

Yellow perch (Juvenile),    FT,  M            93
Perca flavescens
Species Mean
 Acute Value
   (ug/l)
     137


     102



     102
Reference

Smith, et al. 1978
                  Smith, et al.  1978
                  Smith, et al. 1978
                  Smith, et al. 1978
Cairns & Scheler,
1958

Patrick, et al,
1968

Henderson, et al.
1961

Cairns & Scheler,
1963

Smith, et al. 1979
Smith, et al. 1979
                  Smith, et al. 1978
                  Smith, et al. 1978
                  Smith, et al. 1978
                  Smith, et al. 1978
                                                     B-13

-------
Table 1.   (Continued)
Species
Yellow parch (Juvenile),
Perca flavescens
Yellow perch (juvenile),
Perca flavescens
Yellow perch (Juvenile),
Perca flavescens
Yellow perch (juvenile),
Perca flavescens
Copepod,
Acartla clausl
Mysld shrimp,
Hysldopsls bah la
Mysld shrimp,
Mysldopsls btgelowt
Winter flounder,
Pseudop leuronectes
amer 1 cana

Method*
FT, M
FT, M
FT, M
FT, M
S, U
S, U
S, U
S, U
Species Mean
LC50/EC50 Acute Valve
(itfl/l) (ug/1)
74.7
94.7
101
107 125
SALTWATER SPECIES
30 30
93 93
124 124
372 372
Reference
Smith, et
Smith, et
Smith, et
Smith, et
U.S. EPA,
U.S. EPA,
U.S. EPA,
U.S. EPA,
al. 1978
al. 1978
al. 1978
al. 1978
1980b
19605
19806
1980b
* S = static,  FT  »  flow-through, U » unmeasured, M * measured
                                       B-14

-------
                      Table 2.   Chronic  values for cyanide
Species
Isopod,
Asellus communls
Scud,
Gammarus pseudol Imnaeus
Brook trout,
Salvellnus font! nails
Fathead minnow,
PI map hales promelas
B 1 ueg 1 1 1 ,
Lepomls macrochlrus

Test*
LC
LC
LC
LC
as
LlMltS
(tifl/l)
FRESHWATER SPE
29-40
16-21
5.6-11.0
13.3-20.2
9.3-19.8
Chronic
Value
CIES
34
18
7.6
16
14
Reference
Oseld & Smith, 1979
Oseid & Smith, 1979
Koenst, et al. 1977
Llnd, et al. 1977
Klmbal 1, et al. 1978
* LC - Ufa  cycle or partial life cycle;  ELS = early  life stage
                            Acute-Chronic Ratios
Species
Isopod,
Ase 1 1 us coomun 1 s
Scud,
Ganmarus pseudol Imnaeus
Brook trout,
Sa 1 ve 1 1 nus font 1 na 1 i s
Fathead minnow,
Plroephales promelas
Acute
Value
(uq/l)
2,326
167
103
141
Chronic
Value
tug/D
34
18
7.8
16
Ratio
68
9.3
13
8.8
                                              B-15

-------
TabU 2.   (Continued)
                            Acute-Chronic Ratios
            Species

            Bluegll I,
            Lepomls macrochlrus
Chronic
 Value
 (ua/D
  14
                                           B-16

-------
Table 3.   Species neon acute values and acute-chronic ratios for cyanide
ink*
15
14
13
12
11
10
9
8
7
6
5
4
3
Species
FRESHWATER
1 sopod,
Asel lus communls
Midge,
Tany tarsus dlssimllls
Mosqultoflsh,
Gambusla afflnls
Snail,
Physa heterostropha
Goldfish,
Carasslus auratus
Scud,
Gammarus pseudol Imnaeus
Guppy,
Poecl lla retlculata
Blueglll,
Lepomls macrochlrus
Fathead minnow,
Plmephales promelas
Yel low perch.
Per ca flavescens
Brook trout,
Salvellnus fontlnalls
Largemouth bass,
Mlcropterus sal mo Ides
Black cr apple,
Pomoxls nigromaculatus
Species Mean Species Mean
Acute Value Acute-Chronic
(ua/D Ratio
SPECIES
2,326 68
2,240
639
431
318
167 9.3
147
137 9.8
125 8.8
125
103 13
102
102
                                                         B-17

-------
Table 3.  (Continued)
Rank*      Species

   2       Cladoceran,
           Daphnla putex

   I       Rainbow trout,
           SaImo galrdnerI
Species Mean
Acute Value
   (ug/l)

       83
       57
Species Mean
Acute-Chronic
    Ratio
                          SALTWATER SPECIES
           Winter flounder,
           Pseudopleuronectes
           amerlcana

           Mysld shrimp,
           Mysldopsls blgelowl

           Mysld shrimp,
           Mysldopsls bah I a

           Copepod,
           Acartla clausl
      372
      124
       30
* Ranked from least sensitive to most sensitive based on species mean
  acute value.

  Freshwater Final Acute Value » 52 pg/l

  Final Acute-Chronic Ratio = 14.8

  Freshwater Final Chronic Value = (52 iig/O/M.8 - 3.5 ug/l
                                       B-18

-------
                       Table 4.   Plant values for cyanide
Species
Blue-green alga,
Mlcrocystls aeruglnosa
Green alga,
Prototheca zopfI

Green alga,
Chiorel la sp
    Effect

 FRESHWATER SPECIES

90* kill



 SALTWATER SPECIES
                    Result
                    (yg/l)
                     7,990
Respiration
Inhibition
                     3,000


Enzyme Inhibition   30,000
                                                               Reference
Fitzgerald, et al.
1952
Webster & Hackett,
1965

Nelson 4 Tolbert,
1970
                                             B-19

-------
TnbU  5.  Other data for cyanide

Species
Snai 1,
Gonlobasls 1 1 vescens
Snail,
Lymnaea emarglnata
Snal 1 (embryo),
Lymnaea spp.
Sna 1 1 ,
Physa Integra
Scud,
Gammarus pseudol Imnaeus

Cladoceran,
Daphnla magna
Mayfly,
Stenonema rubrum
Caddlsf ly,
Hydropsyche sp
Coho salmon,
Oncorhynchus klsutch
Chinook salmon (juvenile),
Oncorhynchus tshawytscha
Rainbow trout (juvenile),
Salmo galrdnerl
Rainbow trout (adult),
Sa Imo galrdner 1
Rainbow trout (adult),
Salmo galrdnerl

Duration
48 hrs
48 hrs
96 hrs
48 hrs
98 days
96 hrs
48 hrs
48 hrs
2 hrs
64 days
250 min
2 min
8 min

Effect
FRESHWATER SPECIES
LC50
LC50
LC50
LC50
Competition with
Asel lus affects
HCN toxlclty
LC50
LC50
LC50
Swimming speed
reduced
21% reduction In
blomass
Approximate median
survival time
Mean survival time
Mean survival time
Result
(U9/I)
760,000
3,300
51,900
1,350
9
160
500
2,000
10
20
200
2,000
300

Reference
Cairns, et al. 1976
Cairns, et al. 1976
Dowden & Bennett,
1965
Cairns, et al. 1976
Oseld 4 Smith, 1979
Dowden & Bennett,
1965
Roback, 1965
Roback, 1965
broderlus, 1970
Negllskl, 1973
Dep. Scl. Ind. Res.,
1956
Herbert i Merkens,
1952
Herbert i Merkens,
1952
                               B-20

-------
Table 5.  (Continued)
Species
Duration
Rainbow trout (adult),
Sal mo galrdner 1
Rainbow trout (adult),
Sal mo galrdnerl
Rainbow trout (adult),
Sal mo galrdner!
Rainbow trout (adult),
Sal mo galrdnerl
Rainbow trout (adult),
Sal mo galrdnerl
Rainbow trout (adult),
Sal mo galrdnerl
Rainbow trout (adult),
Salmo galrdnerl
Rainbow trout (adult),
Salmo galrdnerl
Rainbow trout (adult),
Salmo galrdnerl
Rainbow trout,
Salmo galrdnerl
Rainbow trout (Juvenile),
Salmo galrdner I
Rainbow trout (juvenile),
Salmo galrdnerl
Rainbow trout (juvenile),
Salmo galrdnerl
Rainbow trout (yearling),
Salmo galrdnerl
12 min
12 mln
24 min
72 mln
90 mln
2,525 mln
1,617 mln
3,600 mln
4,441 min
48 hrs
9 days
4 days
9 days
21 days
Mean survival time
Mean survival time
Mean survival time
Mean survival time
Mean survival time
Mean survival time
Mean survival time
Mean survival time
Mean survival time
LC50
Weight gain reduced
Increased respira-
tion rate
L I ver damage
(necroblosls)
65$ reduction in
weight gain
                Result
Effect          (uq/|)
                                                                 250
                                                                 200
                                                                  180
                                                                  160
                                                                  140
                                                                  100
                                                                  90
                                                                  80
                                                                   70
Reference

Herbert 4 Merkens,
1952

Herbert 1 Merkens,
1952

Herbert & Merkens,
1952

Herbert 4 Merkens,
1952

Herbert 4 Merkens,
1952

Herbert 4 Merkens,
1952

Herbert 4 Merkens,
1952

Herbert 4 Merkens,
1952

Herbert & Merkens,
1952
                                                                  68     Brown, 1968
                                                                   10     Dixon,  1975
                                                                   10     Dixon, 1975
                                                                   10     Dixon, 1975
                                                                  20     Speyer, 1975
                                                                          B-21

-------
Tabla 5.  (Continued)
Species
Rainbow trout (yearling),
Sal mo galrdnerl
Rainbow trout (Juvenile),
Sa lino gairdner 1
Rainbow trout,
Sal mo galrdnerl
Rainbow trout.
Sal mo gairdnerl
Atlantic salmon,
Sal mo salar
Brook trout (fry),
Salvellnus fontlnalls
Brook trout (fry),
Salvellnus font) nails
Brook trout (fry),
Salvellnus fontlnalls
Brook trout (fry),
Sa 1 ve 1 1 nus font 1 na 1 Is
Brook trout (fry),
Sa 1 ve 1 1 nus f ont 1 na 1 1 s
Brook trout (fry),
Salvellnus fontlnalls
Brook trout (fry),
Sa 1 ve 1 1 nus font 1 na 1 Is
Brook trout (fry),
Salvellnus fontlnalls
Duration
21 days
20 days
IS days
18 days
58 days
15.2 mln
10.8 mln
11.7 mln
26 mln
58 mln
210 mln
130 hrs
27 days
Effect
75< reduction In
swimming abl 1 Ity
Abnormal oocyte
development
Production of
s per ma togon 1 a
reduced by 13J
Production of
sperma togon 1 a
reduced by 50$
Teratogenlc
effects to embryos
Death
Death
Death
Death
Death
Death
Death
lOOJt survival
Rasult
(ug/l)
20
10
10
30
10
8,640
4,290
2,130
853
392
217
50
20
Reference
Speyer, 1975
Lesnlak, 1977
Ruby, et al. 1979
Ruby, et al. 1979
Leduc, 1978
Karsten, 1934
Karsten, 1934
Karsten, 1934
Karsten, 1934
Karsten, 1934
Karsten, 1934
Karsten, 1934
Karsten, 1934
                                              3-22

-------
Table 5.  (Continued)
Species
Brook trout (Juvenile),
Salvellnus font Ina Its
Brook trout (juvenile),
Salvellnus fontlnalls
Brook trout (juvenile),
Salvellnus fontlnalls
Brook trout (juvenile),
Salvellnus fontlnalls
Brown trout (fry).
So lino trutta
Brown trout (fry).
Sal mo trutta
Brown trout (fry).
Sal mo trutta
Brown trout (fry),
Sal mo trutta
Brown trout (juvenile),
Salmo trutta
Brown trout (juvenile),
Salmo trutta
Brown trout (juvenile),
Salmo trutta
Brown trout (juvenile),
Salmo trutta
Fathead minnow,
Plmephales promelas
Fathead minnow (juvenile),
Plmephales promelas
Duration
3.6 days
40 days
25.5 mln
90 days
8.2 mln
8.9 mln
8.2 mln
140 mln
6.58 mln
15 mln
30.1 mln
5 hrs
48 hrs
5 days
Effect
Let ha I
Not lethal
75} reduction In
swimming endurance
Reduced growth
Death
Death
Death
Death
Geometric mean
time to death
Geometric mean
time to death
Geometric mean
time to death
Oxygen uptake
Inhibited
LC50
LC50
Result
(up/I)
80
50
10
33
8,030
4,140
2,070
217
1,006
510
320
25
240
120
Reference

Nell, 1957
Nell, 1957
Nell, 1957
Koenst, et al. 1977
Karsten, 1934
Karsten, 1934
Karsten, 1934
Karsten, 1934
Burdlck, et al. 1958
Burdlck, et al. 1958
Burdlck, et al. 1958
Carter, 1962
Black, et al. 1957
Cardwel 1, et al.
1976
                                            B-23

-------
TabU 5.  (ContlMi«l)
Specie*
Fathead minnow (juvenile),
Plmephales prcunelas
Fathead minnow (juvenile),
Plmephales promelas
Fathead minnow (embryo),
Plroephales promelas
Fathead minnow (embryo),
Plmephales promelas
Fathead minnow (embryo),
Plmephales promelas
Fathead minnow (embryo),
Plmaphalas promelas
Fathead minnow (embryo),
Plmephales promelas
Fathead minnow (embryo),
Plmephales promelas
Fathead minnow (embryo),
Plmephales promelas
Black-nosed dace,
Rhlnlchthyfi atratulus
Channel catfish (juvenile),
Ictalurus punctatus
Guppy (juvenile),
Poecllla ratlculata
Stickleback,
Gasterosteus aculeatus
Threesplne stickleback
(adult),
Gasterosteus aculeatus
Duration
28 days
56 days
96 hrs
96 hrs
96 hrs
96 hrs
95 hrs
96 hrs
96 hrs
24 hrs
26 hrs
120 hrs
90 mln
824 mln
Effect
Reduced growth In
length
Reduced growth In
length and weight
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
Threshold
concentration
Depressed respira-
tion rate to 32 %
of norrna 1
Median survival
time
Result
(HO/I)
35
62
347
272
201
123
186
200
206
220
161
236
1,040
134
Reference
Llnd, et al. 1977
Llnd, et al. 1977
Smith, et al. 1978
Smith, et al. 1978
Smith, et al. 1978
Smith, et al. 1978
Smith, et al. 1978
Smith, et al. 1978
Smith, et al. 1978
Llpschuetz & Cooper,
1955
Card we 1 1, et al.
1976
Chen, 1968
Jones, 1947
Broderlus, 1973
                                       B-24

-------
Table 5.  (Continued)
Species

Threesplne stickleback
(adult),
Gasterosteus aculeatus

Threesplne stickleback
(adult),
Gasterosteus aculeatus

Blueglll (juvenile),
Lepomls macrochlrus

Blueglll (juvenile),
Lepomls macrochlrus

Blueglll (Juvenile),
Lepomls macrochlrus

Blueglll (juvenile),
Lepomls macrochlrus

Blueglll (juvenile),
Lepomls macrochlrus

Bluegll I (juvenile),
Lepomls macrochlrus

BluegllI (juvenile),
Lepomls macrochlrus

Blueglll (juvenile),
Lepomls macrochlrus

BluegllI (juvenlle),
Lepomls macrochlrus

Blueglll (adult),
Lepomls macrochlrus

Blueglll (adult),
Lepomls macrochlrus

Blueglll (adult),
Lepomls macrochlrus
Duration
642 mln
412 mln
202 mln
260 mln
351 mln
258 mln
352 mln
655 mln
48 hrs
48 hrs
72 hrs
48 hrs
Effect
Median survival
time
Median survival
time
Median survival
time
Median survival
time
Median survival
time
Median survival
time
Median survival
time
Median survival
time
LC50
LC50
LC50
LC50
289 days     Survival reduced
289 days     No reproduction
                                  Result
                                  (pg/1)     Reference

                                     170     BrOder I us, 1973
                                     237     Broderlus, 1973
                                     198     Broderlus, 1973
                                     194     Broderlus, 1973
                                     165     Broderlus, 1973
                                     165     Broderlus, 1973
                                     144     Broderlus, 1973
                                     127     Broderlus, 1973
                                     134     Cardwell, et al.
                                             1976

                                     280     TurnbulI, et al.
                                             1954

                                     154     Doudoroff, et al.
                                             1966

                                     160     Cairns, et al. 1965
67.8   Klmball. et al. 1978
 5.4   Klmball, et al. 1978
                                                       B-25

-------
Tabie 5.  (Continued)
Species                      Duration
                 Effect
Sinai imouth bass
(Juvenlle),
Micropterus uoloniieui

Sinai iffiouth bass
(juvenile),
Mi croptorus ciolofiiieii!

Sinsi I mouth bass
(Juvenlle),
Micropterus doiosiieu!
SmalImouth  bass
(Juvenlle),
Mlcropterus do Iomleu I
 7.8 mm    Geometric mean
            time to death
12.4 mIn    Geometric mean
            time to death
15.4 win    Geoinetric mean
            time to death
Smal Imouth  bass                30.6 mln
(Juvenlle),
Mlcropterus dolornleu I

Smal Imouth  bass                42.8 mln
(juvenile),
Mlcropterus do IomIeuI
Smal Imouth  bass               133  mln
(Juvenlle),
Mlcropterus  dolorn leu I

Smal Imouth  bass               290  mln
(Juvenlle),
Mlcropterus  do lorn leu I

Largemouth  bass                 2  days
(Juvenlle),
Mlcropterus  sal mo Ides

Yellow  perch (embryo),         96  hrs
Perca flavescens
            Geometric mean
            time to death
            Geometric mean
            time to death
80.5 mln    Geometric mean
            time to death
            Geometric mean
            time to death
            Geometric mean
            time to death
            Significant
            Increases  In
            opercular  rate

            LC50
Result
(ltg/'i)     Reference

 i,980     Burdick, et  ai.  1958
 1,430     Burdick, at  ai.  1958
   978     Burdick, at  ai.  !958
   755     Burdick, et  al.  1958
   478     Burdick,  et  al.  1958
   338     Burdick,  et  al.  1958
   243     Burdick, et  al.  1958
    175     Burdick,  et  al.  1958
    40     Morgan  & Kuhn,  1974
   281     Smith,  et  al.  1978
                                                         B-26

-------
Table 5.  (Continued)
Species
Oyster,
Crassostrea sp.

Oyster,
Crassostrea sp.
Duration          Effect

          SALTWATER SPECIES
                              10 mln      Activity
                                          suppression

                               3 hrs      Activity
                                          Inhibition
                                                               Result
                                                               (ug/l)     Reference
                                      150     Usukl, 1965
                                  30,000     Usukl, 1965
                                                            B-27

-------
                                  REFERENCES

Anderson, P. and L. Weber.   1975.   Toxic  response  as  a quantitative function
of body size.  Toxicol. Appl. Pharmacol.  33: 471.

Black, H.H., et  al.   1957.   Industrial waste guide—by-product  coke.   Proc.
llth Ind. Waste Conf.   Purdue Univ.  41: 494.

Broderius, S.J.  1970.  Determination  of  molecular hydrocyanic  acid  in  water
and studies of the chemistry and  toxicity to fish  of  the nickelocyanide com-
plex.  M.S. thesis.  Oregon State University, Corvallis.

Broderius, S.J.  1973.  Determination  of  molecular hydrocyanic  acid  in  water
and  studies  of  the  chemistry  and  toxicity  to  fish  of metal-cyanide  com-
plexes.  Ph.D.  thesis.  Oregon State University,  Corvallis.

Broderius,  S.,  et  al.  1977.   Relative  toxicity  of   free  cyanide and  dis-
solved  sulfide  forms  to  the   fathead minnow,  Pimephales  promelas.   Jour.
Fish. Res. Board Can.   34: 2323.

Brown, V.M.   1968.   The  calculation  of  the acute toxicity  of mixtures  of
poisons to rainbow trout.   Water Res.  2:  723.

Burdick,  G.E., et  al.   1958.  Toxicity of cyanide to  brown trout  and  small-
mouth bass.  N.Y. Fish Game Jour.  5: 133.
                                     B-28

-------
Cairns,  J.,  Jr. and  A.  Scheier.  1958.   The  effect of periodic  low  oxygen
upon  toxicity  of various  chemicals  to aquatic  organisms.   Proc.  12th  Ind.
Waste Conf. Purdue Univ. Eng. Ext. Ser. No. 94, Eng. Bull.   42: 165.

Cairns,  0.,  Jr. and A.  Scheier.   1963.  Environmental effects  upon  cyanide
toxicity  to  fish.   Notulae  Naturae,  Acad.  Natural Sci.,  Philadelphia,  No.
361.

Cairns,  J.,  Jr., et al.   1965.   A comparison of the  sensitivity to  certain
chemicals  of  adult  zebra  danios  Brachydanio  rerio (Hamilton-Buchanan)  and
zebra  danio  eggs with  that  of  adult  bluegill  sunfish Lepomis  macrochirus
Raf.  Notulae Naturae, Acad,  Natural  Sci., Philadelphia, No. 381.

Cairns,  J., Jr.,  et  al.   1976.  Invertebrate  response  to  thermal shock  fol-
lowing  exposure to  acutely  sub-lethal concentrations  of  chemicals.   Arch.
Hydrobiol.  77: 164.

Cardwell,  R.,  et al.   1976.  Acute  toxicity of  selected toxicants  to  six
species  of  fish.  Ecol. Res.  Ser.  EPA  600/3-76-008.   Environ.  Res.  Lab.,
U.S. Environ.  Prot.  Agency, Duluth, MN.  117 p.

Carter, L.  1962.  Bioassay of trade  wastes.  Nature.  196:  1304.

Chen,  C.W.   1968.    A   kinetic  model  of  fish  toxicity  treshold.    Ph.D.
thesis.  University of California,  Berkeley.
                                     B-29

-------
Department  of Scientific  and  Industrial  Research.   1956.   Water  pollution
research 1955.  H.M. Stationery Off. London.

Dixon, O.G.   1975.  Some  effects  of chronic cyanide  poisoning on the growth,
respiration and liver tissue of rainbow  trout.   M.S.  thesis.   Concoraia Uni-
versity, Montreal.

Doudoroff,  P.   1956.   Some experiments  on the toxicity of  complex cyanides
to fish.  Sewage Ind.  Wastes.   28:  1020.

Doudoroff,  P.  1976.  Toxicity to fish of  cyanides  and related compounds:  A
review.  Ecol. Res. Series.  EPA  600/3-76-038.   Environ. Res. Lab., U.S.  En-
viron. Prot. Agency, Duluth, MN.   154 p.

Doudoroff, P., et al.   1966.  Acute toxicity  to  fish  of solutions containing
complex  metal  cyanides,   in relation to  concentrations of molecular  hydro-
cyanic acid.  Trans. Am.  Fish.  Soc.  95:  6.

Dowden,  B.F.  and  H.J.  Bennett.    1965.   Toxicity of  selected  chemicals  to
certain animals.   Jour.  Water  Pollut. Control  Fed.  37: 1308.

Fitzgerald, G.P., et al.   1952.   Studies on chemicals  with selective toxici-
ty to blue-green  algae.   Sewage Ind. Wastes.  24:  888.

Henderson,  C.,  et  al.    1961.   The effects  of  some  organic cyanides  (ni-
triles)  on  fish.   Proc.   15th  Ind.  Waste Conf. Purdue  Univ.  Eng.  Ext.  Ser.
No. 106. Eng. Bull.  45:  102.
                                     B-30

-------
Herbert, D.W.M.  and  J.C.  Merkens.   1952.  The toxicity  of  potassium cyanide
to trout.  Jour. Exp. Biol.  29: 632.

Izatt,  R.M.,  et  al.   1962.   Thermodynamics  of  metal-cyanide coordination.  I.
pK,   H°,  and   S°  values   as  a  function   of  temperature  for  hydrocyanic
acid dissociation in aqueous solution.  Inorg.  Chem.  1:  828.

Jones,  J.R.E.  1947.  The  oxygen consumption of Gasterosteus aculeatus  L.  in
toxic colutions.  Jour.  Exp. Biol.   23: 298.

Karsten, A.  1934.    Investigations  of the  effect  of cyanide on  Black  Hills
trout.  Black Hills Eng.  22: 145.

Kimball, G.,  et al.  1978.   Chronic  toxicity of  hydrogen  cyanide  to  blue-
gills.  Trans. Am.  Fish. Soc.  107:  341.

Koenst, W., et al.   1977.   Effect of  chronic exposure  of brook  trout to sub-
lethal concentrations of hydrogen cyanide.  Environ. Sci. Technol.  11:  883.

Leduc,  G.   1978.  Deleterious  effects  of  cyanide on early life stages  of
Atlantic salmon (Salmo salar).   Jour.  Fish.  Res. Board  Can.   35:  166.

Lee, D.  1976.   Development  of  an  invertebrate bioassay  to  screen  petroleum
refinery  effluents  discharged  into  freshwater.    Ph.D.  thesis.   Virginia
Polytechnic Inst. State  University,  Blacksburg.
                                     8-31

-------
Lesniak,  J.A.   1977.   A  histological  approach  to  tne  study of  sublethal



cyanide effects on rainbow  trout  ovaries.   M.S.  thesis.   Concordia  Universi-



ty, Montreal.







Lind, D.,  et  al.   1977.   Chronic effects of  hydrogen  cyanide  on  the fathead



minnow.   Jour. Water Pollut. Control Fed.  49: 262.








Lipschuetz, M.  and A.L.  Cooper.  1955.  Comparative toxicities of  potassium



cyanide  and potassium  cuprocyanide  to the  western blacknosed  dace  (Rhinich-



tys atratulus meleagris).  N.Y. Fish Game Jour.  2: 194.







Morgan,  W.S.G.  and P.C.  Kuhn.   1974.   A  method to monitor  the  effects  of



toxicants  upon breathing  rates  of  largemouth  bass   (Micropterus  salmoides



Lacepede).  Water Res.  8: 67.








Negilski,   D.S.  1973.   Individual   and  combined  effects  of  cyanide  penta-



chlorphenol and zinc  on  juvenile Chinook  salmon and  invertebrates  in  model



stream communities.  M.S. thesis.  Oregon State University, Corvallis.







Neil, J.H.  1957.   Some  effects of  potassium  cyanide on  speckled  trout  (Sal-



velinus  fontinalisj.   In:   Papers presented at 4th Ontario  Ind.  Waste  Conf.



Water Pollut. Adv.  Comm., Ontario Water Resour. Comm.,  Toronto,  p.  74-96.








Nelson,  E.B.  and  N.E.  Tolbert.  1970.   Glycolate  dihydrogenase in  green  al-



gae.  Arch. Biochem. Biophys.  141:  102.
                                     B-32

-------
Oseid,  D.  and L. Smith.   1979.   The effects of  hydrogen  cyanide  on Asellus



communis and  Ganvnarus pseudolimnaeus  and  changes  in  their  competitive  re-



sponse  when   exposed  simultaneously.   Bull.   Environ.   Comtam.  Toxicol.



21: 439.







Patrick, R.,  et  al.   1968.   The  relative sensitivity of diatoms, snails, and



fish to twenty  common constituents of industrial wastes.   Prog.  Fish-Cult.



30: 137.







Roback, S.S.   1965.   Environmental  requirments  of Trichoptera.   In:   Bio-



logical problems  in water pollution.  3rd  Seminar   (1962),  R.A.  Taft  Sanit.



t-.ig. Center, Cincinnati, Ohio.  p. 118-126.







Ruby,  S.M.,  et  al.   1979.   Inhibition  of  spermatogensis  in  rainbow  trout



during chronic cyanide poisoning.  Arch.  Environ. Contam. Toxicol.  8:  533.








Smith,  L.L.,  Jr.,  et al.   1978.   Acute  toxicity  of  hydrogen  cyanide  to



freshwater fishes.  Arch. Environ. Contam.  Toxicol.   7: 325.







Smith, L.L.,  Jr., et  al.  1979.   Acute  and  chronic toxicity of HCN to  fish



and  invertebrates.   Ecol.  Res.  Ser.  EPA-600/3-79-009.  Environ.  Res.  Lab.,



U.S. Environ.  Prot.  Agency, Duluth, MM.  115 p.







Speyer, M.R.   1975.   Some  effects  of cnronic  combined arsenic  and  cyanide



poisning  on  the physiology of  rainbow  trout.   M.S.  tnesis.   Concordia



University, Montreal.
                                     3-33

-------
Turnbull,  H.,  et  al.   1954.    Toxicity  of  various  refinery  materials  to
freshwater fish.   Ind. Eng. Chem.  46: 324.

U.S. EPA.  1980a.  Unpublished  laboratory data.   Environ.  Res.  Lab.,  Duluth,
Minnesota.

U.S. EPA.   1980b.   Unpublished  laboratory data.  Environ. Res.  Lab.,  Narra-
gansett, Rhode Island.

Usuki,   I.   1965.   A  comparison  of  the effects of  cyanide and azide  on  the
ciliary  activity  of   the  oyster gill.  Sci.  Rep.  Tohoku  University,  Fourth
Sci.  22: 137.

Wallen,  I.E.,  et al.   1957.   Toxicity to  Gambusia affim's of  certain  pure
chemicals in turbid waters.  Sewage Ind.  Wastes.   29: 695.

Webster,  D.A.  and   D.P.  Hackett.   1965.    Respiratory chain  of  colorless
algae.     I.   Chlorophyta  and   Euglenophyta.    Plant  Physiol.   Lancaster.
40: 1091.
                                     B-34

-------
Mammalian Toxicology and Human Health Effects



                           INTRODUCTION



     Cyanides are defined as hydrogen cyanide  (HCN) and  its  salts.



The  toxicological effects of  cyanides  are based upon their  poten-



tial for rapid conversion by mammals to HCN.   Various organic  com-



pounds containing the  cyanide  (CN)  moiety which may have a  poten-



tial for conversion  to HCN  in  vivo will not be considered in  this



document.  Cyanides have long been  feared  for  their high  lethality



and  their  fulminating  action.   At the  present  time, however,  cya-



nides do  not constitute an  important  or  widespread environmental



health problem.  Almost all examples of human  cyanide poisoning or



adverse environmental effects in  the past  have  involved occupation-



al exposures  or  relatively  localized  sources  of pollution.    Cya-



nides are  uncommon  in  U.S.  water supplies  and in the atmosphere.



Although some food plants clearly can cause acute  cyanide  poisoning



if ingested in sufficient amount, the evidence  associating cyanide



compounds in other plants with chronic  neuropathies is not convinc-



ing.



     Some evidence  suggests  that the uses  of  cyanide  in the  U.S.



are increasing, and, therefore, continued vigilance in the form of



monitoring is indicated.  However, a number of  properties  and char-



acteristics of cyanide  indicate  that it will probably remain  only a



potential pollutant  or  one of  secondary  concern.   For example,  cya-



nide has a low degree of persistence in the environment,  and it is



not  accumulated   or  stored  in  any mammalian  species   that  has



been studied.   In  keeping  with  the  latter,   a sizeable  body of
                               C-l

-------
experimental evidence  suggests that cyanide  has  an unusually  low



degree of  chronic  toxicity.   It does  not  appear  to be mutagenic,



teratogenic, or carcinogenic.



     No  new  evidence was  encountered  to  suggest  that the Public



Health Service  (PHS) drinking  water  standard for  cyanide set  in



1962  should  be  lowered  (National  Institute  Occupational Safety



Health (NIOSH), 1976).



                             EXPOSURE



     The  toxicological  effects of  cyanides  are  based upon their



potential for rapid conversion by mammals  to  HCN.



     Cyanide production in the U.S. is now over 700 million pounds



per year  and appears  to  be  increasing  steadily  (Towill,  et  al.



1978).  The sources and  industrial  uses of  cyanide  compounds in  the



United States  have  recently  been  reviewed  exhaustively  (NIOSH,



1976;  Towill, et al.  1978).   Briefly,  the major industrial users of



cyanide in the  U.S.  are  the producers of steel, plastics,  synthetic



fibers and chemicals, and the electroplating  and metallurgical  in-



dustries.  In  addition  to  these  industries (see  Table 1) , cyanide



wastes are discharged into the environment from the pyrolysis of a



number of synthetic  and natural materials  and from chemical,  bio-



logical,   and  clinical  laboratories.   Although wool,  silk, poly-



acrylonitrile,  nylon, polyurethane, and paper are all  said to lib-



erate  HCN  on  combustion,  the  amounts  vary widely with the condi-



tions. As yet  there  is  no  standardized fire toxicity test  protocol



in the U.S. (Terrill, et al.  1978).



     Despite numerous  potential sources of pollution, cyanide  is



relatively uncommon  in most  U.S. water supplies.   A survey of  969
                               C-2

-------
                                                              TABLE 1
                                                                             *
                                                     Inorganib Cyanide Wastes
Source and
I II
Bureau of
III IV
the Census regions
V VI
Total
VII VIII IX
                                                 Annual waste production (Ib/year)

Cyanides from               fi           e           t           f.          t.          r.           t.           e.          c,           i,
   electroplating 2.78  x  10  6.07  x  10  6.86  x  10   0.96 x 10° 1.04 x 10  0.49 x 10° 0.77  x  10  0.15 x 10  2.20 x 10  21.32 x 10

E'aint sludge
   cyanides       1,000       9,900       13,800       2,900      3,850      2,150      3,350       550         7,300      44,900
   sludge         0.92  x  106  8.12  x  106  11.32 x 106 2.40 x 106 3.16 x 106 1.76 x 106 2.74  x  106  0.44 x 106 5.97 x 106 36.83 x 106

I'aint residue               ccc           cccccct
   cyanides       0.18  x  10  0.57  x  10  0.62  x  10   0.23 x 103 0.47 x 10  0.20 x 10D 0.30  x  10  0.13 x 10  0.41 x 10  3.11 x 10

   old paint      13 x  106    41  x  106    44  x  106    16 x 106   34 x 106   14 x 106   21  x  106    9  x  106    29 x 106   221 x 106

                                                         Stored  wastes  (lb)

Sodium (;yanide                1,400                                                                16                    1,416
Calcium cyanide                                                                       180                   25           205
('oppet cyanide                  100                                                                32                      132
L'otassium cyanide                                               2                                                           2
liilvt-r cyanide                                                                                    16         10            26
Potass iuin
   ferr icyanide                                                 4                                                           4
pot ,jiia iuin
   fecrocyanide                                                            12                                              12
 Souice:  Ottinger, et  al.  1973.



                                                                    C-3

-------
U-,S. public  water  supply systems in 1970 revealed no cyanide con-



centrations  above  the  mandatory limit (McCabe, et  al.  1970).    In



2,595 water  samples, the highest cyanide concentration  found was 8



ppb  and  the  average  concentration was  0.09  ppb  (Towill,  et al.



1978).   In part, this must be ascribed to the volatility of undis-



sociated hydrogen  cyanide  which would be the  predominant  form  in



all  but highly  alkaline  waters.   Also,  in part, cyanide ion would



have a decided  tendency  to  be  "fixed"  in the form of insoluble or



undissociable complexes by trace metals.   Cyanide  may complex irre-



versibly with heavy metals in water supplies and  thereby be biolo-



gically inactivated  in terms  of toxicity attributable  to cyanide.



Conversely,  some  cyanide  complexes,  such  as  nitroprusside,  are



readily dissociable  and  elicit  toxic  responses directly attribut-



able to the  release  of cyanide  in  vivo.   In view of  the increased



production and  uses  of  cyanide  in  the  U.S.,  however, continued



vigilance in the form of monitoring is certainly  indicated, parti-



cularly in the  proximity of known potential sources  of pollution.



Techniques for  monitoring  have been  reviewed  elsewhere  (NIOSH,



1976; Towill, et al. 1978).



Ingestion from Water



     As noted above, cyanide is an uncommon pollutant in most U.S.



water supplies,  and documented examples of levels in  excess of the



1962, U.S. Public  Health Service  limits  (U.S.  PHS,  1962)  are ex-



tremely rare. No  human cases of illness  or death  due  to cyanide in



water  supplies  are  known.   The lack of  such  documentation,  of



course, cannot be accepted complacently.  It  is entirely possible



that pulse discharges of  industrial wastes result  in  high localized
                               C-4

-------
concentrations which  have  escaped detection, but general  recogni-



tion of the high toxicity of cyanide has made its removal  standard



practice  in  most  industries  (Reed,  et al.   1971).   Fortunately,



known methods for  cyanide removal  including  alkaline chlorination,



hypochlorite  treatment,  reaction  with  aldehydes,  electrolytic



decomposition,  exposure to  ionizing  radiation,  and  heating are



effective and relatively economical  (Lawes,  1972; Watson,  1973).



     A  few  accidents  have  resulted in massive fish  kills,  some



livestock deaths,  and environmental damage.   Cyanide, unknowingly



released from a  sewage  plant  in  Oak Ridge,  Tenn.,  was responsible



for the death of 4r800 fish  in Melton Hill Lake near  the sewage out-



fall (The Oak Ridger, 1975).  About 1,500 drums (30 and 55 gallon)



containing cyanides  disposed  of near  Byron,  Illinois  resulted  in



long-range environmental damage  and livestock death.  Surface  water



runoff  from  the  area contained  up  to  365  ppm cyanide  (Towill,  et



al. 1978).



Ingestion from Food



     Except  for  certain  naturally occurring  organonitriles   in



plants, it is uncommon to find cyanide in foods in the U.S.   Addi-



tionally, there  is no data  available  indicating  bioconcentration  of



cyanide.  The  U.S.  EPA Duluth laboratory states  that the bioconcen-



tration factor  will  be  very close to  zero  (Stephan,  1980).   For



criterion calculation purposes, however, a tissue content approach-



ing that of  the  surrounding medium is assumed.   In  higher plants



the major group  of organonitriles are the  cyanogenic  glycosides,



and at  least  20 distinct compounds  are  known.   Perhaps  the  best



known of this group  is  the  compound amygdalin, which  is  found  in
                               C-5

-------
many parts of  the  cherry laurel and the seeds of cherries,  plums,
peaches, apricots, apples,  and  pears.   Amygdalin is the chief  in-
gredient in Laetrile.  Both Laetrile and amygdalin-containing fruit
pits have been  implicated  as  causes of acute cyanide poisoning  in
humans  (Braico, et al.  1979;  Gosselin, et al. 1976).  The release
of free cyanide from cyanogenic glycosides can be effected by acid
hydrolysis or  most  rapidly by /^-glucosidases, enzymes present  in
plants  and  in  the intestinal microflora of mammals  but  found  in
only trace amounts in animal  tissues (Conchie, et al. 1959).
     Another naturally occurring group  of organonitriles are  called
the pseudocyanogenic glycosides of  which  the  best known example  is
cycasin from the Cycadaceae.  As  implied by the name, cyanide  re-
lease from these compounds is  unlikely  to occur in vivo  since alka-
line hydrolysis is  required (Miller,  1973).   Cycasin and related
glycosides are  highly  toxic and  their ingestion along with  food-
stuffs  has  been  implicated  in  a  variety of  so-called "tropical
neuropathies"  and  amblyopias  (Osuntokun,  1968).    Although   these
neurological disturbances have frequently been cited  in  the litera-
ture (Towill, et al.  1978) as examples  of "chronic cyanide poison-
ing," the evidence for  that extrapolation is  indirect  and inconclu-
sive.   The  failure  of  repeated attempts  to  produce similar syn-
dromes with pure hydrogen cyanide or its salts  (see following dis-
cussion),  strongly  suggests  that   the  neuropathies  produced   by
cycasin-containing foods are  due  to other unrecognized toxins,  to
the cycasin per se,  or  to uncharacterized toxic metabolites,  rather
than to cyanide.
                               C-6

-------
     Other organonitrlies found in plants  include  the  lathyrogenic



compounds, such  as ^-glutamyl-^-cyanoalanine,  the glucosinolates



such  as  glucobrassicin,  and  the  cyanopyridine  alkaloids such  as



ricinine  and  indoleacetonitrile  (Towill, et  al.  1978).   Although



many of  these  are  toxic to  mammals,  no evidence links their  toxi-



city to cyanide poisoning.



Inhalation



     Hydrogen  cyanide  vapor  is  absorbed rapidly through  the  lungs



{Gettler and St. George,  1934).  Because HCN has a pKa of 9.2 and



exists primarily as  the acid  under biological conditions, absorp-



tion  across  the alveolar membrane should  be rapid  (Wolfsie and



Shaffer, 1959).  Human  inhalation  of  270 ppm HCN  vapor  brings  death



immediately, while 135  ppm  is fatal  after  30 minutes  (Dudley,  et



al. 1942).



     Cyanide absorption following  inhalation of  very low concentra-



tions  is  indicated by  the  observation  that smokers  have  higher



thiocyanate levels  in  plasma  and  other  biological fluids than  do



nonsmokers (Wilson  and  Matthews, 1966).   Cyanide  levels usually are



not significantly different in smokers as compared with nonsmokers



(Pettigrew and Fell, 1973; Wilson  and  Matthews,  1966), since cya-



nide absorbed  from  inhaled  tobacco smoke  is rapidly  converted  to



thiocyanate  (Johnstone and  Plimmer,  1959;  Pettigrew and   Fell,



1973).  Inhalation  of cyanide  salt dusts is also dangerous because



the cyanide will dissolve  on  contact with  moist mucous  membranes



and be  absorbed  into  the bloodstream  (Davison,  1969;  Knowles and



Bain,  1968).

-------
     The  so-called  distinctive  odor of bitter almonds ascribed  to



HCN does not necessarily serve as a warning of exposure.   The  abil-



ity  to  smell hydrogen cyanide  appears  to be a genetically deter-



mined trait.   Individuals  vary  widely from being unable  to detect



the  odor  to being extremely  sensitive  to it (Kirk and  Stenhouse,



1953).



Dermal



     Hydrogen cyanide, in either liquid or vapor  form, is absorbed



through the  skin  (Drinker,  1932;  Potter,  1950;  Tovo, 1955; Walton



and Witherspoon,  1926).   Absorption  is  probably increased if  the



skin is cut, abraded, or  moist.   Many  accidents  involving skin con-



tamination  also  involve  inhalation exposure; the contribution  due



to skin absorption  in  these cases  is  difficult to assess.  Potter



(1950) described a case  in  which liquid HCN  ran over  the  bare hand



of a worker wearing a fresh air  respirator.   Cyanide  inhalation  was



prevented, but the worker collapsed into deep unconsciousness  with-



in five minutes, suggesting significant percutaneous  absorption.



                       PHARMACOKINETICS



Absorption



     Probably the common commercial inorganic cyanides are rapidly



absorbed from  the  stomach  and duodenum.   Certainly,  the   human  ex-



perience in  regard to  the rapidly  lethal  effects  (Gosselin, et  al.



1976) of ingested cyanides  is in accord with  the above, but experi-



mental studies  which actually define quantitatively  the rates  of



penetration  are not available.



     Hydrogen cyanide  is a  weak acid with a  pKa of 9.2.   Thus,  the



acid milieu  of  the  stomach would  greatly favor  the   undissociated
                               C-8

-------
species, HCN, which should  further hasten absorption.  Even  at  the



physiological pH of 7.4,  however,  cyanide would  exist  predominantly



as the unionized moiety  which would serve to  facilitate  its  trans-



fer among various body compartments (see previous discussion).   In



accord with the theory of nonionic diffusion  cyanide  would be pre-



dicted to accumulate in  body compartments which are at a higher  pH



{more alkaline) than blood.   At present,  no evidence can be cited



to substantiate directly that prediction.



     It has long been common knowledge that  hydrogen cyanide  gas  or



vapors  are  rapidly  absorbed  via  the lungs,  producing  reactions



within a  few  seconds  and  death within minutes (Gosselin,  et al.



1976).  Hydrogen cyanide has been used as the instrument of execu-



tion for convicted  criminals  in some  states of the U.S.  primarily



because of its  rapid lethal effects on inhalation of high concen-



trations.



     Hydrogen cyanide gas or solutions are absorbed  through the in-



tact skin much  more  readily than are  the ionized  salts  which are



less  lipid  soluble  (Wolfsie  and Shaffer,  1959).    Absorption   is



probably increased in both cases if  the skin has been  cut or abrad-



ed.   Alleged  cases of human  skin absorptions,  however,  are often



complicated by the  possibility of concomitant  inhalation of cyanide



gas.   Again,  quantitative estimates of the  rate of penetration  of



skin by various forms of cyanide are not available.



Distribution



     Cyanide  is distributed  to all  organs  and  tissues via  the



blood,  where  its concentration in  red  cells  is greater than that  in



plasma by a factor of  two  to  three.   Presumably,  the accumulation
                               C-9

-------
Qf cyanide  in  erythrocytes  is a reflection of its binding  to met-



hemoglobin.  Methemoglobin  is found  normally in the blood  of non-



smokers  at  concentrations as high as  2  percent  of the total cir-



culating pigment  (Smith  and Olson, 1973).   However,  there may  be



other  factors  as  yet unrecognized which favor the accumulation  of



cyanide  in red cells.  Cyanide may also  accumulate locally  in body



cells  because  of  binding  to  metalloproteins or  enzymes  such  as



catalase or cytochrome c oxidase (Smith,  et al.   1977).  The possi-



bility  of  concentration  differences  due  to  pH  gradients  between



body compartments was mentioned  above.   Certainly, one would pre-



dict that cyanide would readily cross the placenta, but again quan-



titative data are lacking.



Metabolism



     By  far,  the  major pathway  for  the  metabolic detoxication  of



cyanide  involves  its conversion  to thiocyanate via the  enzyme rho-



danese  (de Duve, et  al. 1955).   Rhodanese  is  widely distributed  in



the  body,  but  the  highest  activity  is  found  in  mammalian liver



(Table 2).   The rate  of the  rhodanese reaction in vivo  is limited  by



the availability of  the endogenous  sulfur-containing substrate, the



identity of  which is still  unknown.   Thiosulfate can  serve  as a



substrate for  rhodanese  with  a  high degree  of  efficiency both  in



vivo  and in vitro   (Chen  and Rose,  1952; Himwich  and Saunders,




1948).



     Alternative  minor  metabolic pathways  for  cyanide metabolism



include  conjugation  with cysteine  to  form 2-iminothiazolidene-4-



carboxylic acid,  a  reaction  that  is  said  to proceed nonenzymati-



cally  (Figure  1).    In rats  given a total  dose  of 30  mg  over  an
                               C-LO

-------
                             TABLE 2

Rhodanese Activity In Tissues Of The Dog,  Rhesus Monkey, Rabbit,  And Rat
               (mg CN converted  to SCN~ per gram of  tissue)
Dog
Tissue
Suprarenals
whole

cor tex
medulla
Liver

iii ain
cor tex
caudate nucleus
midbrain
cere be 11 ura
medulla
Spinal cord
cervical
lumbar
sacral
Heart
Kidney
Tcstes
Epidydymis
Ovar Ics
Lung
Spleen
Muscle
Intest i ne
duodenum
jejunum
Eye
Optic nerve
Rhesus Monkey
Number Number
Range3 of Range3 of
observations observations

2.14-
(5.46,
2.86-
0.27-
0.78-
(4.91,

0.34-
0.27-
0.52-
0.21-
0. 38-

0.15-
0.12-
0.16-
0.11-
0.42-
0.32-
0.29
0.42
0.16-
0. 10-
0.03-

O.OS-
0.04
0.02
0. 35

3.60
4.50)
5.62
1.12
1.46
6.28)

0.92
1.06
1.35
1.22
1.52

1.08
0.84
1.41
0. 14
0.74
0.41


0.17
0. 14
0.19

0. 11




6

2
2
7


7
7
6
7
7

7
4
4
6
6
5
1
1
3
2
6

3
1
1
1

0.14-1




.35



10.98-15.16
(5.

0.27
0.34-0
0. 22-0
0.33
0.49-D

0.56-0
0.20-0
0.23-0
0.48-0
2.46-3
0.38-0


0. 11-0
0.12-0
0.23-0





98)


.50
.80

.85

.57
.42
.28
.82
.58
.46


.21
.34
.57






3



4


1
2
2
1
2

2
2
2
3
4
3


2
2
3






1.



7.


1.
0.
1.
0.
0.

0.
0.
0.

6.
0.

0.
0.
0.
0.





Rabbit
Rat
Number Number
Range of Range o£
observations observations

24-3.



98-18


41-1.
13-0.
17-1.
63-1.
91

89-0.
35-1.
59-1.

20-7.
32-0.

30
40
20
18






94



.92


44
18
39
24


90
74
10

69
36











2



9


2
2
2
2
1

2
2
3

3
2

1
1
1
1






0.27-0.41 2



14.24-28.38 9


0.70-0.72 2

0.73-1.13 2



0.16-0.18 2
0.23-0.27 2
0.56-0.74 2

10.44-11.08 2
1.24-1.61 2










                           Oil

-------
                                                     TABLE 2  (Cont.)
                                   Dog
Rhesus Monkey
                                                                                   Rabbit
                                                                                                             Rat
Tissue
Salivary gland, parotid
Lymph node
Pancreas
Thy 10 id
Anterior pituitary
Whole blood
Ery throcy tes
ljlasma
Range3
0
0
0
0
0
0
0
0
.05-0.
.08-0.
.14-0.
.05-0.
.26
.01-0.
.01-0.
.01
36
13
28
94
02
02
Number Number Number Number
of Range3 of Range of Range ol
observations observations observations observations
3 0.99
2
4 0.12-0.44
3
I
2
2
1
1
2


Figures in parentheses are single observations falling outside  the  normal  range.
SOULCC-:  Adapted from tiimwich and Saunders,  1948.
                                                              C-12

-------
                           NITRILES
           CN-
             minor path
2-imino-thiazolidine-
  4-carboxylic acid
      HCN
  in expired air
 Major path
*  CNS- -
,CN- pool
  Excretion
                            CO,
^. cyanocobalarmn
    HCNO    HCOOH
        metabolism of
        one-carbon
        compounds
                some excreted
                  in urine
                           FIGURE 1

               Fate  of  Cyanide  Ion  in the Body

                    Source:   Williams, 1959
                              C-13

-------
eight-day period, this pathway accounts for no more than 15  percent



of the  total cyanide  (Wood  and  Cooley, 1956).  A very  small  frac-



tion of  the  total cyanide  is  bound by hydroxocobalamin, probably



less than 1 percent (Brink, et al.  1950).  A  small amount (about  1



to 2 percent)  is excreted unchanged as HCN via the \lungs (Friedberg



and Schwarzkopf, 1969).   By  reactions  that are not well  understood,



cyanide gains access to  metabolic pathways for one-carbon compounds



and is converted to formate and  to  carbon dioxide.



Excretion



     As estimated  in  rats  given 30 mg  sodium cyanide  intraperi-



toneally over a period of eight  days,  80  percent of the  total cya-



nide is excreted in the urine in the  form of  thiocyanate (Wood and



Cooley, 1956).   Because  the  fate of cyanide  is largely  determined



by a single metabolic pathway, one  would  predict that  it would fit



a relatively simple  pharmacokinetic model,  e.g., first order kinet-



ics in plasma,  but such  detailed  analyses have not  been  made.  Cya-



nide does not appear  to  accumulate significantly  in  any body com-



partment with repeated doses or  chronic exposures.



     Because the liver contains  the highest activity of  rhodanese,



it is possible  that pre-existing liver disease might slow the rate



of cyanide metabolism, but no studies  appear  to address  this ques-



tion.   No inhibitors of  rhodanese are known  which  are active in



vivo.



                             EFFECTS



Acute,  Subacute, and Chronic Toxicity



     Hydrogen cyanide and its alkali  metal salts  are  chemicals of



high inherent lethality to man and  other mammals.   The mean lethal
                              C-14

-------
dose of these substances by mouth  in human adults is in the range of
50 to 200 mg  (1 to 3 mg/kg), and death is rarely delayed  more  than
an hour  (Gosselin, et  al.  1976).   In respiratory exposures  to hy-
drogen cyanide gas, death occurs in 10  to  60 minutes at approximate
ambient  concentrations of  0.1 to  0.3 mg/1  (or  100  to  300  ppm)
(Table 3).  In nonfatal poisonings recovery is generally  rapid and
complete.
     The acute effects of cyanide  poisoning  in all obligate aerobic
species can be ascribed directly or indirectly to a single specific
biochemical lesion,  namely the inhibition of cytochrome  c oxidase
(Gosselin, et al.  1976).   Inhibition of  this  terminal enzyme com-
plex  in  the  respiratory electron  transport  chain  of mitochondria
impairs both oxidative  metabolism  and the  associated process  of ox-
idative  phosphorylation  (Lehninger,  1975).    The  ensuing syndrome
has  been well  characterized  in   man  and  in laboratory animals
{Gosselin, et al.  1976).   In its  major features  cyanide  poisoning
resembles the effects of acute  hypoxia  whether the latter  is  due to
airway obstruction or  to  the  absence  of  oxygen  (anoxic  hypoxia),
carbon monoxide poisoning  (anemic  hypoxia),  or shock (stagnant or
hypokinetic hypoxia), all of which result in  a decreased  supply of
oxygen to peripheral tissues.
     Cyanide poisoning differs from other types of hypoxia in that
the oxygen tension in peripheral tissues usually remains  normal or
may even be elevated (Brobeck,  1973).   This paradoxical difference
arises because the effect of cyanide  is to block the utilization of
oxygen by aerobic cells, a  novel  condition  referred  to  as  histo-
toxic  hypoxia.     The  organ  systems  most   profoundly   affected,
                              C-15

-------
                                                TABLE 3

                   Human Response To Inhaled Cyanide And Cyanide-Containing Compounds
       Compound
Cyanogen
                         Cyanide  concentration
                      Response
16
Nasal and eye irritation after
  6 to 8 rain
                                                                                                    Reference

Hydrogen cyanide
(mg/liter )
0.3
0.2
0.15
0.12-0.15
(ppm)
270
181
135
110-135

Immediately fatal
Fatal after 10-mln exposure
Fatal after 30-min exposure
Fatal after % to 1 hr or
later, or dangerous to life

Prentiss, 1937
Prentiss, 1937
Prentiss, 1937
Fassett, 1963
McNerney and
  Schrenk,1960
Cyanogen chloride





Cyanogen bromide





0.40
0.120
0.005

0.0025

0.40
0.035
0.006



159
48
2

I

92
8
1.4



Fatal after 10-win exposure
Fatal after 30-min exposure
Intolerable concentration,
10-min exposure
Lowest irritant concentration,
10-min exposure
Fatal after 10-min exposure
Intolerable concentration
Greatly irritating to
conjunctiva and the mucous
membranes of the respiratory
system
Prentiss, 1937
Fassett, 1963
Fassett, 1963

Fassett, 1963

Prentiss, 1937
Prentiss, 1937
Prentiss, 1937



                                                    C-16

-------
however, are the same as those impaired in any hypoxia irrespective



of etiology, namely  the  brain and the heart because of  their  high



dependence on oxidative metabolism.  Two signs associated with cya-



nide poisoning  in man  (Gosselin,  et  al. 1976)  follow  from  the  pre-



ceding:  (1) the failure to utilize  molecular  oxygen  in  peripheral



tissues results in abnormally high concentrations of  oxyhemoglobin



in the venous return which accounts  for a  flush or  brick-red  color



of the skin; and  (2)  attempts to compensate for the  inhibition of



oxidative metabolism leads to increased demands on glycolysis  which



accounts for a metabolic (lactic) acidosis.



     A special but less unique effect  of cyanide is stimulation of



the chemoreceptors of  the  carotid body which elicits a  character-



istic pattern of  reflex  activity (Heymans and Neil, 1958).   Since



the nature of these chemoreceptors is  unknown,  it is  possible  that



the effect of cyanide on them  is  due  also in some way to  the  inhibi-



tion of  cytochrome c  oxidase.    Stimulation  of the  carotid   body



chemoreceptors by cyanide results in an immediate, well-sustained,



and marked  augmentation  of the  respiration.   Circulatory  effects



which often  accompany  the  increase  in ventilation include  a  tran-



sient rise in blood  pressure  which  is probably secondary to a re-



flex sympathetic  discharge.   The rise in  blood pressure is often



accompanied by a bradycardia  which  some  authorities insist is not



due to  the  common baroreceptor  reflex via  the vagus  nerves.   The



pressor response is  followed  by  a fall in blood pressure to hypo-



tensive levels  from  which  the victim may not  recover (Heymans and



Neil,  1958).
                               C-17

-------
     The other prominent effect of cyanide on the respiration  is a



direct depression or fatal arrest which is the result of an action



of cyanide  at the level of  the  brain  stem nuclei responsible for



the control of breathing.  In poisoned victims, the heart beat in-



variably outlasts breathing movements.  The cardiac irregularities



often noted may be secondary to respiratory embarrassment, but di-



rect histotoxic effects of cyanide on myocardial cells are an even



more likely mechanism.



     Massive  oral doses  or  concentrated  respiratory exposures may



result  in   a  sudden unconsciousness  which  may  simply  represent



fainting secondary  to  the  delayed drop  in blood  pressure  noted



previously.  Presumably, the histotoxic hypoxia triggers a massive



peripheral  vasodilation  resulting in  orthostatic  hypotension and



collapse.   The  sequence  of  events is  slower on  exposure  to  lower



concentrations (Table 3) and victims may experience anxiety, confu-



sion, vertigo, and giddiness before loss of consciousness.  Uncon-



sciousness   is followed  by asphyxial  convulsions which may be vio-



lent and generalized.  Opisthotonus,  trismus, and incontinence are



common.  The  seizures may be followed by a brief period of paraly-



sis or rigidity and by death from apnea (Gosselin, et al.  1976).



     Despite  the high lethality of large single doses or acute re-



spiratory exposures  to  high vapor concentrations of  cyanide,  re-



peated sublethal doses  do not result  in cumulative adverse effects.



Thus, cyanide is  an  example of a chemical which  has  a high acute



toxicity, but an unusually low  degree  of subacute  or chronic toxic-



ity.   Hertting, et al.  (1960)  administered doses  (0.5 to  2 mg/kg)



of sodium  cyanide  once  or  twice  each  day to dogs.   This usually
                               C-18

-------
resulted in acute toxic signs from which the  animals recovered com-
pletely  within  half an hour.   This regimen was  continued over a
period  of  15 months  with  no evident  pathophysiologic  changes  in
organ function or permanent alteration  in intermediary metabolism.
Similarly, rats  tolerated  the  equivalent of  an acute oral LD   of
potassium cyanide each day for  25 days  when it  was mixed with their
regular diet (Hayes, 1967).
     Workers at American Cyanamid  (1959) fed to beagle dogs a diet
containing 150 ppm  sodium  cyanide  for  30 days  without observing a
significant  effect  on  their  food  consumption,  hematologic  para-
meters, behavioral characteristics, or  microscopic changes  in their
organs  or  tissues.   Howard and Hanzal  (1955)  fed  a diet that had
been fumigated with  cyanide gas  and contained the equivalent of 100
to 300 ppm hydrogen  cyanide to  rats for two years, also with essen-
tially  negative  findings.   The  conclusion seems  inescapable that
cyanide, in  substantial but sublethal  intermittent  doses,  can be
tolerated for long periods of time  and perhaps indefinitely.
     It seems reasonable to assume that continuous exposure to some
as yet  undefined, but low concentration of  hydrogen cyanide gas,
could lead inevitably  to  an exhaustion of  the  reserve capacity of
mammals to inactivate and  detoxify cyanide.  The rate at which cya-
nide can be inactivated during acute exposure has been measured in
guinea pigs.   By continuously infusing cyanide solutions intraven-
ously at different  rates,  Lendle  (1964) showed that  at  a  rate of
0.076 mg/kg~ /min"  about  90 percent of the  single  lethal  dose as
determined by "bolus" injection could be detoxified  over the course
of an hour.  When the  rate of  administration was  slowed,  multiple
                              C-19

-------
lethal doses could be tolerated.  Extrapolation to a dose  rate  that



could be  tolerated  indefinitely,  however,  does not seem  justified



with such a highly artificial model system.



Synergism and/or Antagonism



     Since cyanide  acts  by inhibiting cytochrome c oxidase, it  is



reasonable to presume  that any  other  established inhibitor of the



same enzyme would have toxic effects  synergistic  with  (or  additive



to) those of cyanide.  An established example of such a  substance



is sulfide which  is  encountered as hydrogen sulfide gas or as the



alkali metal  salts  (Smith and  Gosselin,  1979).    Sulfide is  even



more potent  than  is cyanide as an  inhibitor  of  cytochrome c  oxi-



dase,  and similarities between  sulfide and cyanide  inhibition  sug-



gest that they act by similar mechanisms  (Nicholls,  1975;  Smith, et



al. 1977). No  specific experimental studies can  be  cited,  however,



on the combined effects  of cyanide and sulfide in either  in vitro



or in vivo systems.



     The  only other  established inhibitor  of cytochrome c oxidase



is  azide  (given  either   as  hydrazoic acid  or  its  alkali  metal



salts).    Azide  is a  much weaker inhibitor  of cytochrome c oxidase



than is cyanide or  sulfide,  and it appears  to act by a different



inhibitory mechanism  (Smith,  et  al.   L977).   Again,  no   specific



studies can be cited to establish whether azide has synergistic or



additive effects in combination with cyanide.



     Although cyanide produces  the cellular equivalent of  hypoxia,



there  is  no  reason  to suppose  that other  causes of hypoxia would



have effects  additive to or synergistic with those o£ cyanide.   By



coincidence one cause  of anemic hypoxia  (Brobeck,  1973), namely,
                              C-20

-------
methemoglobinemia, is a specific antagonist to cyanide  (see  follow-



ing).  Oxygen  has  no  effect on cyanide inhibition of cytochrome c



oxidase  in  vitro,  and  it  does not reverse  the  course of  cyanide



poisoning in vivo.   Since  cyanide  blocks  the  utilization of  molecu-



lar oxygen in peripheral tissues,  its  effects on  oxygen tension are



opposite in direction to those  of  "true"  hypoxia.  Since cytochrome



c oxidase has  a  very  high  affinity for molecular oxygen, it seems



unlikely that  the  oxygen  tension  in peripheral tissues in  cyanide



poisoning is ever  a limiting parameter.



     Cyanide poisoning is specifically antagonized by any chemical



agent capable  of rapidly  generating methemoglobin in vivo  such as



sodium nitrite,  hydroxylamine, amyl nitrite, and a large number of



aromatic amino- and nitro-compounds such  as aniline, p-aminopropio-



phenone, and nitrobenzene  (Smith  and  Olson,  1973).   Methemoglobin



binds cyanide tightly in the form  of the  biologically inactive com-



plex, cyanmethemoglobin.  From a  therapeutic standpoint  there are



several disadvantages to the induction of methemoglobinemia  despite



its established efficacy.   Cyanmethemoglobin is a dissociable com-



plex, and eventually  the dissociation of free cyanide  from it may



result in a  recurrence  of  symptoms.  The procedure  is  limited by



the  concentration  of  methemoglobin that  can be  tolerated  by the



victim,  and  the chemicals used  to  generate methemoglobin have toxic



side effects of  their own (Gosselin, et al.  1976).



     A second therapeutically useful approach to the antagonism of



cyanide   poisoning  is to  provide   an  exogenous substrate  for  the



enzyme rhodanese,  which converts  cyanide  to  the  considerably less



toxic form of thiocyanate.   The endogeneous substrate for rhodanese
                              C-21

-------
is  not  known,  but  p-toluene  thiosulf onate (CH-,CgH4-S02-S~) is 4.5



times  more  active  than  thiosulfate  as   a   substrate   in   vitro



(Sorbo, 1953).   Ethyl thiosulfate (C,H[--S-SO.,-0~) ,  ethyl xanthate
                                     £ J     J


(C2H5OCS2~), diethyl  dithiocarbamate ((C-Hc)2NCS2~)/  hydrosulfite



(S204~) and  colloidal sulfur  are all inactive  as  substrates for



rhodanese  (Sorbo,  1953).   It  is  probable   that  other  sulfur com-



pounds as yet untested can also serve as substrates for rhodanese.



     A variety of  cobalt  compounds  effectively antagonize cyanide



poisoning,  presumably by  reacting  chemically with  free  cyanide,



e.g., cobaltous chloride, hydroxocobolamine, and cobalt EDTA.  The



latter two  compounds have been  used in humans  (Gosselin,  et al.



1976).  Although oxygen  alone  has no effect on cyanide poisoning,



it  is  said  to  potentiate  the  anti-cyanide actions  of thiosulfate



and particularly the  thiosulfate-nitrite combination  (Way,  et al.



1966).



Teratogenicity, Mutagenicity, and Carcinogenicity



     Data are not available on teratogenic, mutagenic, or carcino-



genic effects of cyanide,  nor  do  there  appear to be any published



studies with analagous compounds  from which one might postulate the



possible adverse effects of long-term, low-level  exposure.  As pre-



viously indicated,  a number of studies designed to show chronic or



cumulative adverse  effects yielded  only negative findings.   It is



possible  that  cyanide has anti-neoplastic  activity;  at  least one



study  (Perry,  1935)  reported a low  therapeutic  index for cyanide



against rat sarcomas.



     In contrast, thiocyanate,  the major product  of cyanide detoxi-



fication  in vivo,  has  produced developmental  abnormalities in the
                              C-22

-------
chick  (Nowinski  and Pandra, 1946)  and  ascidian embryo  (Ortolan!,
1969)  at  high concentrations.   Unfortunately,  these studies with
thiocyanate cannot  be extrapolated  to man, nor can those of Hrizu,
et al.  (1973), who  reported a  cytostatic effect of thiocyanate on
human KB cells in culture as well as an  increased survival rate in
mice  inoculated  with  Ehrlich  ascites  tumor cells.    Again,  the
amounts  used  preclude  any  meaningful extrapolation  to human pa-
tients.  Thus, there  is no  evidence that chronic exposure to cya-
nide results  in teratogenic, mutagenic, or carcinogenic effects.
                              C-23

-------
                    CRITERION FORMULATION



Existing Guidelines and Standards



     The  U.S.  Public Health  Service Drinking Water  Standards of



1962 established 0.2 rag  CN~/1  as  the  acceptable criterion for water



supplies.  In addition  to defining the 0.2 mg/1 criterion for cya-



nide, the PHS  set forth an "objective"  to  achieve concentrations



below 0.01 mg CN~/1 in water "because proper treatment will reduce



cyanide levels to 0.01 mg/1 or less"  (U.S. PHS, 1962).  The Canadi-



an government has adopted criterion and objective concentrations of



0.2 mg CN~/1  and 0.02 mg CN~/1, respectively.   The latter figure



represents  the  lower limit  of detection by  colorimetric  methods



(Health and Welfare, Canada, 1977).



     The U.S. PHS criterion was  based on cyanide toxicity to fish



and not to man.   Obviously,  a disparity exists between the exposure



condition for  man and  for  fish.   The cited  human experience in-



volved discrete single doses by mouth whereas  the fish data are de-



rived from continuous  total body exposure.   The  latter conditions



are not a very realistic model from which to assess the human haz-



ard.  Even chronic occupational  exposures  of  men to hydrogen cya-



nide gas allows for respite at the end of each working day.



Current Levels of Exposure



     Since cyanide  is encountered  only  infrequently in water sup-



plies or in  the  atmosphere  and  since  long-term and large-scale mon-



itoring has not been conducted,  insufficient data exist to estimate



current levels of exposure of the general population.   A number of



factors contribute  to  the  rapid  disappearance of cyanide from wa-



ter.  Bacteria and protozoa may degrade cyanide by converting it to
                               C-24

-------
carbon dioxide  and  ammonia (Leduc,  et al. 1973).  Cyanide  is  con-



verted to  cyanate during  chlorination of water  supplies  (Rosehart



and Chu,  1974).   An alkaline pH favors the oxidation by  chlorine,



whereas  an acid pH  favors  volatilization of HCN  into  the  atmos-



phere.  As cited, cyanide concentrations above 8 ppb  were  not found



in a survey of 2,595 water  samples collected  throughout the  United



States (Towill, et al.  1978).  Thus,  these concentrations  were  well



below the  objective  levels  established by  the PHS.



Special Groups at Risk



     Although  it  was speculated that  the  elderly and the  debili-



tated individuals in our population may be at  special risk with re-



spect to cyanide, no experimental or  epidemiological  studies can be



cited to prove the point.



Basis and  Derivation of Criteria



     As shown in Table 4, the criterion of 0.2 mg CN~/1 (200 pg/1)



allows for safety factors ranging from 41 to  2,100.   El Ghawabi,  et



al. (1975)  studied  the  effects  of  chronic cyanide exposure  in the



electroplating sections of three Egyptian factories.   A total of 36



male employees with  exposures up to 15 years were studied and  com-



pared with a  control group of 20 normal,  nonsmoking males.   Only



minimal differences with respect to thyroid gland size and function



were found.  The El Ghawabi study was given considerable weight in



formulating  the  NIOSH  recommendations for  occupational  exposure



which gives a safety factor of 41 when applied to drinking water  by



the usual  extrapolations  (Table 4).    Finally,  a safety  factor  of



2,100 is obtained using the results  of a two-year chronic  feeding



study in rats.  When fed  at the rate of 12 mg/kg per day over  the
                               C-25

-------
                                              TABLE 4

                             Basis and Derivation of Cyanide Criterion
Exposure Route Species Calculated Margin.of
Levels Daily Exposure Safety
9.2 mg/m3 Inhalation Han 60.6 «gb 152
2.5 mg/m3 Inhalation Man 16.5 mgb 41
12 rag/kg Oral Rat 840 mgc 2100
Investigator
t
El Ghawabi, et al. 1975
NIOSII, 1976
Howard and
Hanzal, 1955
aNOAEL
 Based on 100% retention and on alveolar exchange of 6.6m  for 8 hours.

cRat  data   converted  to  human   equivalent  assuming   food  consumption  of   60  g/kg   for   rats   and   70
 kg human.

 Daily   exposure   compared  with   0.4   rag/day  exposure   from  the  consumption   of  2   1   water   containing
 0.2 mg/1.
                                                C-26

-------
 equivalent  of  a  lifetime,  these  rats  showed  no  overt  signs of cya-

 nide  poisoning,  and hematological values  were  normal.   Gross  and

 microscopic examinations of tissues revealed no abnormalities.  The

 only  abnormality found was an elevation  of  thiocyanate levels  in

 the liver and  kidneys.  Consequently, the ADI for man  is derived by

 taking   the no-observable-adverse-effeet  level  in  mammals  (12

 nig/kg/day)  multiplied  by the weight of  the average man  (70 kg)  and

 dividing by a  safety factor of 100.  This safety factor  was derived

 by methods  discussed  in the Federal Register  (44  FR 15980).   Thus,

     ADI =  12  mg/kg/day x  70 kg -f 100 =  8.4 mg/day.

     The  equation for calculating the criterion for the  cyanide

 content of  water  given an  Acceptable  Daily Intake is

     2X +   [Jo.0065)   (X0  = ADI

Where

     2 = amount of drinking water, I/day

     X = cyanide  concentration in water, mg/1

     0.0065 =  amount of fish consumed, kg/day

     F = bioconcentration  factor, mg  cyanide/kg  fish  per
         mg cyanide/1 water

     ADI =  limit  on daily  exposure for a 70 kg person =8.4 mg/day

          2X + (0.0065) (1)X = 8.4

                           X = 4.19 mg/1 (or £2  4.2 mg/1)

     Thus,  the current and recommended  criterion (0.2 mg/1)  has  a

margin of safety  of 21.0 (4. 2 -f- 0.2).

     No new additional evidence was encountered  to suggest  that  the

1962 PHS  Drinking Water Standard  for cyanide  should be  lowered.

The concentration of 0.2 mg/1 or less is easily  achieved by proper

treatment and  concentrations  in  excess  of that  amount have been
                               C-27

-------
encountered only on rare occasions in U.S.  water  supplies.  The ex-
perience since 1962 suggests that 0.2 mg CN~/1 is a safe criterion
for man.
     Although a case could be made for using the  epidemiologic data
(El Ghawari,  et al.  1975)  or the  rat  feeding  study  (Howard and
Hanzal, 1955)  to  derive alternative  higher  criteria,  such an ap-
proach is not recommended at this  time.  The  epidemiologic data was
obtained on a very limited number  of individuals  exposed  by inhala-
tion rather than oral administration, on which there was a statis-
tically significant biological  effect.   In the  rat feeding study,
cyanide was  added  to  the chow by  fumigation.   Consequently,  some
uncertainty exists concerning the actual dose levels.  The current
PHS drinking water  standard  represents  a  body of human experience
which has proven both  protective and achievable.   At  this time, the
epidemiologic data  and  animal  toxicity studies  are  not  of suffi-
ciently high quality to justify  a  water  quality criterion above the
PHS standard.
                               C-28

-------
                            REFERENCES

American Cyanamid Co.  1959.  Report  on  sodium cyanide:  30-Day re-
peated feedings to dogs.  Central Med. Dept.

Braico,  K.T.,  et al.   1979.   Laetrile  intoxication:  Report  of  a
fatal case.  New England Jour. Med.   300:  238.
Brink,  N.G. ,  et  al.   1950.   Vitamin B12:  The  identification  of
vitamin  B,~ as  a  cyano-cobalt  coordination  complex.    Science.
112: 354.
Brobeck, T.R.  1973.   Best and  Taylor's  Physiological Basis  of Med-
ical Practice.  9th ed.  Williams and Wilkins Co., Baltimore.

Chen, K.K. and C.L. Rose.   1952.   Nitrite and thiosulfate  therapy
in cyanide poisoning.   Jour. Am. Med. Assoc.  149: 113.

Conchie, J. ,  et  al.   1959.  Mammalian glycosidases distribution  in
the body.  Biochem. Jour.  71: 318.

Davison, V.  1969.  Cyanide poisoning.  Occup. Health.  21: 306.

de  Duve,  C. ,  et  al.    1955.    Tissue   fractionation studies:  6.
Intracellular distribution patterns of enzymes in  rat-liver  tissue.
Biochem. Jour.  60: 604.
                              C-29

-------
Drinker, P.   1932.   Hydrocyanic  acid  gas poisoning by absorption



through the skin.  Jour. Ind. Hyg.  14: 1.







Dudley, B.C.,  et al.   1942.  Toxicology  of acrylonitrile  (vinyl



cyanide):  II. Studies of effects  of  daily inhalation.   Jour. Ind.



Hyg. Toxicol.  24: 255.







El Ghawabi, S.H., et al.  1975.  Chronic cyanide exposure:   a  clini-



cal,  radioisotope,  and  laboratory study.    Br.  Jour.  Ind. Med.



32: 215.







Fassett, D.W.  1963.  Cyanides and Nitriles.   In;  D.W.  Fassett and



D.D.  Irish,  (eds.)   Industrial Hygiene  and Toxicology.   2nd ed.



John Wiley and Sons, Inc.,  New York.   2: 1991.







Friedberg, K.D.  and H.A. Schwarzkopf.   1969.  Blausaureexhalation



bei der  Cyanidvergiftung  (The  exhalation of  hydrocyanic  acid  in



cyanide poisoning).   Arch.  Toxicol.  24: 235.







Gettler,  A.O.  and  A.V.  St.  George.    1934.   Cyanide poisoning.



Jour.  Clin. Pathol.   4: 429.







Gosselin,  R.E.,  et  al.  1976.  Clincial  Toxicology of Comraerical



Products.   4th ed.  Williams and Wilkins Co., Baltimore, Maryland.







Hayes, W.T.,  Jr.   1967.  The  90-dose LD5Q and a chronicity factor  as



measures of toxicity.  Toxicol. Appl. Pharmacol.  11:  327.
                               C-30

-------
Health and Welfare, Canada.  1977.  Cyanide-drinking water criteria



review.  Document  furnished by Dr.  Peter Toft.







Hertting, G.,  et  al.   1960.   Untersuchungen uber die  Folgen  einer



chronischen Verabreichung  akut toxicher Dosen  von Natriumcyanid  an



Hunden.  Acta. Pharmacol.  Toxicol.   17: 27.







Heymans, C. and E. Neil.   1958.   Cardiovascular Reflexes  of Chemo-



receptor Origin.  In;  Reflexogenic Areas of the Cardiovascular Sys-



tem.  J.A. Churchill, Ltd., London.  p. 176.







Himwich, W.A.  and  J.P.  Saunders.   1948.   Enzymatic conversion  of



cyanide to thiocyanate.  Am. Jour.  Physiol.  153: 348.







Howard, J.W. and R.F. Hanzal.  1955.  Chronic  toxicity for  rats  of



food  treated  with hydrogen  cyanide.    Jour.  Agric.   Food  Chem.



3: 325.







Hrizu, D., et al.   1973.   Cytostatic effects  of potassium  sulfocya-



nate  in  vivo and  in  vitro.   Arch.  Roum.  Pathol.  Exp. Microbiol.



32: 155.







Johnstone, R.A.W. and J.R. Plimmer.  1959.  The chemical  constitu-



tents of tobacco and  tobacco smoke.  Chem. Rev.  59: 885.







Kirk, R.L. and N.S. Stenhouse.   1953.   Ability to smell  solutions



of potassium cyanide.  Nature.  171: 698.
                               C-31

-------
Knowles, E.L.  and  J.T.B.  Bain.   1968.   Medical cover required  in
large  scale  production of  cyanides  and hydrocyanic  acid.   Chem.
Ind.  8: 232.

Lawes, B.C.  1972.   Control of cyanides  in plating shop effluents:
What's on the shelf now?  Plating.  59:  394.

Leduc, G. , et al.  1973.  Use  of  sodium cyanide  as  a  fish eradicant
in some Quebec lakes.  Natur.  Can.  100: 1.

Lehninger, A,L.  1975.  Biochemistry.   2nd ed.   Worth Publishers,
Inc., New York.

Lendle, L.  1964.  Werkungsbedungungen von blausaure  und schwefel-
wasserstoff  und moglichreiten  der  vergiftungsbehandlung.    Jap.
Jour. Pharmacol.  14: 215.

McCabe, L.J., et al.  1970.  Survey of community water supply sys-
tems.  Jour. Am. Water Works Assoc.  62: 670.

McNerney, J.M. and  H.H.  Schrenk.   1960.   The  acute  toxicity  of cya-
nogen.  Am. Ind. Hyg. Assoc. Jour.  21:  121.

Miller, L.P.  1973.   Glycosides.   In;  Phytochemistry.  Vol.  I.  Van
Nostrand Reinhold Co., New York.   p. 297.
                               C-32

-------
National Institute for Occupational Safety and Health.  1976.  Cri-
teria for recommended standard...Occupational exposure  to  hydrogen
cyanide and cyanide salts (NaCN, KCN and Ca(CN)2).   NIOSH Publ.  No.
77-108.   Dep.  Health  Edu.  Welfare.    U.S.  Gov.   Printing  Off.,
Washington, O.C.

Nicholls, P.  1975.  The effect of sulfide on  cytochrome aa.,.   Iso-
steric and  allosteric  shifts of the reduced  peak.   Biochem.  Bio-
phys. Acta.  396:  24.

Nowinski, W.W. and J. Pandra.   1946.  Influence of  sodium  thiocya-
nate on the development of the  chick embryo.  Nature.   157:  414.

Ortolani, G.   1969.   The action of sodium thiocyanate  (NaSCN)  on
the  embryonic  development of  the  ascidians.    Acta Embryol. Exp.
27-34.

Osuntokun,  B.O.   1968.   An  ataxic  neuropathy in  Nigeria.   Brain.
91: 215.

Ottinger, R.S.,  et al.   1973.   Recommended methods for  reduction,
neutralization,  recovery, or disposal of  hazardous waste. Vol  1.
EPA-670/2-73-053-a, U.S. EPA, Washington, D.C.

Perry, I.H.   1935.   The effect  of  prolonged  cyanide  treatment  on
body and tumor growth in rats.   Am. Jour. Cancer.    25:  592.
                               C-33

-------
rettigrew,  A.R.  and G.S. Fell.   1973.   Microdiffusion method  for



estimation  of  cyanide in whole  blood and  its  application to  the



study  of  conversion  of cyanide   to  thiocyanate.    Clin.   Chem.



19: 466.







Potter, A.L.   1950.   The successful treatment of  two  recent  cases



of cyanide poisoning.  Br. Jour. Ind. Med.   7: 125.







Prentiss, A.M.   1937.   Systemic Toxic Agents.   In:  Chemicals  in



War.  McGraw-Hill Book Co., Inc./ New York.  p. 170.







Reed, A.K., et al.   1971.   An investigation of techniques for  re-



moval of  cyanide  from electroplating wastes.  Rep.  No.  12010  EIE



11/71.  U.S. Gov. Printing Off., Washington, D.C.







Rosehart, R.G.  and R. Chu.   1974.   Cyanide destruction  in mine



wastewater.   Water Pollut. Res. Can.  85.







Smith, L. , et  al.  1977.  The effect of methemoglobin on the inhibi-



tion  of  cytochrome  c oxidase by cyanide,  sulfide  or  azide.   Bio-



chem. Pharmacol.   26: 2247.







Smith, R.P.  and R.E. Gosselin.  1979.  Hydrogen sulfide poisoning.



Jour. Occup. Med.  21: 93.







Smith, R.P.  and M.V.  Olson.   1973.   Drug-induced methemoglobinemia.



Semin. Hematol.  10: 253.
                               C-34

-------
Sorbo,  B.H.    1953.    On the  substrate  specificity  of  rhodanese.



Acta Chem. Scand.  7:  32.







Stephan, C.E.   1980.   Memorandum  to  J. Stara.   U.S.  EPA.   May 5.







Terrill, J.B.,  et al.   1978.   Toxic  gases  from fires.   Science.



200: 1343.







The Oak Ridger.  1975.   State says cyanide caused  lake  fishkill.



Oak Ridge, Tennessee.   September  5.







Tovo,  S.    1955.   Poisoning  due  to  KCM absorbed  through  skin.



Mineria Med.  75: 158.







Towill, L.E.,  et al.   1978.   Reviews of  the environmental effects



of pollutants:  V. Cyanide.  U.S.  EPA.  NTIS-PB  289-920.







U.S. Public Health Service.  1962.   Drinking water standards.   PHS



Publ. No. 956.   U.S. Gov. Printing Off., Washington,  D.C.







Walton, D.C. and M.G. Witherspoon.   1926.  Skin absorption of cer-



tain gases.  Jour. Pharmacol.  Exp. Ther.  26: 315.







Watson, M.R.    1973.   Cyanide  Removal from Water.   In;  Pollution



Control  in  Metal Finishing.   Noyes  Data Corp., Park  Ridge,  New



Jersey,  p. 147.
                               C-35

-------
Way, J.L., et al.  1966.   Effect of  oxygen  in  cyanide  intoxication:



I. Prophylactic protection.   Jour. Pharmacol.  Exp. Ther.  153: 331.








Williams,  R.T.    1959.   Detoxication  Mechanisms.   2nd  ed.   John



Wiley and Sons,  Inc., New York.








Wilson, J. and D.M. Matthews.   1966.  Metabolic  interrelationships



between cyanide,  thiocyanate,  and vitamin  B,- i-n smokers and non-



smokers.  Clin.  Sci.  31: 1.







Wolfsie,  J.H.  and C.B.  Shaffer.  1959.   Hydrogen cyanide.   Jour.



Occup. Med.  1:  281.







Wood, J.L. and S.L. Cooley.   1956.   Detoxication  of  cyanide by cys-



tine.  Jour. Biol. Chem.  218:  449.
                               C-36

-------