CYANIDE in WATER and SOIL: Chemistry, Risk, and Management - Chapter 15 ppsx

15
Toxicity of Cyanide to
Aquatic-Dependent Wildlife
Jeremy M. Clark, Rick D. Cardwell, and Robert W. Gensemer
CONTENTS
15.1 Distribution of Cyanide in the Environment 286
15.2 Exposure Pathways 287
15.3 Mechanisms of Toxicity 287
15.4 Literature Review Methods and Scope 287
15.4.1 Data Quality Determination 288
15.4.2 Data Normalization 288
15.4.2.1 Normalization to mg/kg Body Weight 288
15.4.2.2 Normalization of Toxic Dose to Cyanide Ion 289
15.4.2.3 Endpoint Normalization 289
15.5 Data Analysis 289
15.6 Discussion 290
15.6.1 Route of Exposure — Mammals 290
15.6.2 Route of Exposure — Birds 303
15.6.3 Comparisons between Birds and Mammals 304
15.6.3.1 Drinking Water 304
15.6.3.2 Food 304
15.6.3.3 Direct Injection 304
15.6.4 Simple Cyanide versus Complex Cyanide Compounds 304
15.7 Bioaccumulation of Cyanide 305
15.8 Toxicity Thresholds for Cyanide 305
15.9 Summary and Conclusions 306
Acknowledgments 306
References 307
The U.S. Environmental Protection Agency’s (USEPA) ambient water quality criteria (AWQC) for
cyanide were developed in 1984 [1] and have been used extensively to develop local water quality
standards for protection of aquatic life. New knowledge on the relative toxicity of bioavailable

cyanide species, and the measurement of cyanide species [2] have prompted a reevaluation of the
However, AWQC for protection of aquatic life do not necessarily represent concentrations that would
be protective of the entire aquatic ecosystem. Consideration also should be given to the sensitivity of
wildlife species whose primary habitats are aquatic or are dependent on aquatic life as a food source.
Aquatic-dependent wildlife is comprised of waterfowl, shorebirds (e.g., sandpipers), and aquatic
mammals (e.g., otter, beaver).
285
© 2006 by Taylor & Francis Group, LLC
aquatic toxicity data that serve as the basis of the current national criteria [3; see also Chapter 14].
286 Cyanide in Water and Soil
Here, we review the toxicity of cyanide compounds to aquatic-dependent wildlife exposed via
drinking water and food. Our focus was to evaluate the bioavailability
1
of cyanide from different
exposure pathways and the degree to which toxicity changes when different cyanide compounds
pass from the intestinal tract into the bloodstream. More specifically, the purpose of this review is to
evaluate the following questions:
• What is the relative toxicity of cyanide compounds to aquatic-dependent wildlife?
• Does cyanide toxicity to birds and mammals differ materially by route of exposure
(e.g., drinking water versus dietary exposure)?
• What is the range of toxicity of cyanide compounds and do simple cyanide compounds
differ significantly from complex cyanides in toxicity?
• Does normalization of the toxic dose of a cyanide compound to free cyanide (HCN and
CN
−
) concentration provide a more accurate and comparable estimate of a toxicity
threshold or reference value?
• Which no-effect concentrations appear protective of birds and mammals generally, and
aquatic-dependent wildlife specifically?
Because toxicologic data for aquatic-dependent wildlife species are extremely limited, data for

birds and mammals commonly tested in the laboratory also were used. Testing of surrogate animal
species is standard practice in wildlife risk assessments, as relatively few species have been tested,
compared to the large number of bird and mammal species of concern [5].
15.1 DISTRIBUTION OF CYANIDE
IN THE ENVIRONMENT
Cyanide compounds are used for a wide variety of private and industrial processes and formed as
(SCN
−
) is produced in plants from the family Brassicaceae [2,6]
2
. Anthropogenic sources include
mining operations, manufacture of synthetic fabrics and plastics, pesticides, and production interme-
diates in agricultural chemical production [6,7]. Formation of cyanide compounds during treatment
onment include free cyanide, simple cyanides, metallocyanide complexes, thiocyanate, synthetic
Free cyanide (CN
−
and HCN) appears to be the primary toxic form in the aquatic environment
[8,9]. In aqueous solution below pH 9.2, the majority of free cyanide exists as hydrogen cyanide,
HCN [6]. Simple cyanides typically refer to water-soluble salts of free cyanide such as sodium or
potassium cyanide (NaCN and KCN), respectively. In water, NaCN and KCN completely dissociate
to produce free cyanide, which is a pH-dependent combination of CN
−
Metallocyanide salts produce variable fractions of free cyanide upon dissolution in water, the con-
centrations of which depend on pH and the metal’s affinity for the CN
−
ion (e.g., CdCN
−
, Cu(CN)
−
2

,
Ni(CN)
2−
4
, Zn(CN)
−
3
, Fe(CN)
4−
6
, etc.; see Chapters 2 and 5). Of the metal–cyanide complexes, iron–
cyanide complexes often predominate in surface waters because of the abundance of iron and the
high affinity of CN
−
for Fe
2+
and Fe
3+
(Chapter 5). Most environmentally important complexes
associated with mining and mineral extraction (e.g., gold) are classified as “weak acid dissociable”
(WAD) cyanides [10]. Exceptions are cobalt and iron cyanides, which are not quantified by the WAD
1
The term “bioavailability” is defined in this context as the degree to which a chemical can be taken up by an
organism, subsequently interacting with a biologically important site of action [4].
2
This family includes cauliflower, cabbage, and turnips.
© 2006 by Taylor & Francis Group, LLC
a result of certain chemical reactions (Chapter 4). In addition, they are formed naturally by certain
plants (Chapter 3); for example, cyanogenic glycosides are produced in cassava and thiocyanate
of municipal wastewater can also occur [2; and Chapter 25]. Chemical forms of cyanide in the envir-

nitriles, and organic cyanides (Chapter 2).
and HCN [9; and Chapter 5].
cyanide analytical method [2; and Chapters 5 and 7].
Toxicity of Cyanide to Aquatic-Dependent Wildlife 287
Biogenic sources of cyanide consist of various species of bacteria, algae, fungi, and higher plants
in many food plants and forage crops, and may represent the greatest sources of cyanide expos-
ure to terrestrial mammals [10]. In this regard, cassava (Manhot esculenta) has received the most
study because of its elevated content of organic cyanide compounds (glycosides) and because of its
importance as a major food staple in Asia, Africa, South America, and the Caribbean Islands [11].
15.2 EXPOSURE PATHWAYS
Animals may be exposed to cyanide or cyanide compounds via a number of pathways. They may
ingest food or water containing natural or anthropogenic cyanide. Toxicity from cyanide-producing
(cyanogenic) plants is believed to result from enzymatic release of HCN from the ingested organic
cyanide compound. Hydrocyanic acid is readily absorbed by the guts of birds and mammals [10].
Secondary poisoning
3
of terrestrial vertebrates from feeding on cyanide-poisoned invertebrates and
fish is unlikely, as free cyanide is neither bioaccumulated nor persistent in the environment [1,6,10].
Because secondary poisoning is unlikely, reported anthropogenic cyanide poisonings of wildlife are
usually acute events resulting from water exposure.
15.3 MECHANISMS OF TOXICITY
Toxicity in animals results from the binding of cyanide to the ferric heme form of cytochrome c
oxidase, which is the terminal oxidase in the mitochondrial respiratory chain [6]. This blocks electron
transfer from cytochrome c oxidase to molecular oxygen, thereby inhibiting cellular respiration. This
results in cellular hypoxia even in the presence of normal, oxygenated hemoglobin [6]. Hypoxia
concomitantly causes a shift from aerobic to anaerobic metabolism, resulting in lactate acidosis
that lowers blood pH, and depresses the central nervous system, leading to respiratory arrest and
death [6].
In vivo, the majority of cyanide not complexed with heme iron can be detoxified by combining
with thiosulfate to produce thiocyanate, which is excreted in the urine over a period of several

days [6]. More minor detoxification pathways include exhalation of HCN and conjugation with
cystene or hydroxocobalamin (vitamin B
12
) [6]. Cyanide is readily absorbed into the bloodstream
and binds to hemoglobin forming methemoglobin, which is considered one of the better indicators
of cytotoxicity [6].
15.4 LITERATURE REVIEW METHODS AND SCOPE
Studies on cyanide toxicity to animals were obtained using both literature databases and Internet
search strategies. The terms (wildlife, bird
∗
, avian, shorebird
∗
, waterfowl, amphibian
∗
, “marine
mammal,” “marine mammals”) and (toxic
∗
, ecotoxic
∗
, sensit
∗
) and (cyanid
∗
, metallocyanid
∗
,
organocyanid
∗
) were used to search literature databases: ASFA, BIOSIS, CC Search
®

7 Editions,
Water Resources Abstracts, and Zoological Record in January–February 2003. Various search
engines were used to scan the Internet for relevant articles using the keywords and phrases. These
searches returned 224 records.
Records were retrieved and abstracts or titles screened to judge relevance and utility, yielding
49 records. Of these, 24 were available and reviewed, and 10 were accepted as adequate studies
according to the criteria described in the following section. No data for marine aquatic-dependent
wildlife were found.
3
Secondary poisoning represents toxicity to organisms that consume a cyanide-containing plant or animal.
© 2006 by Taylor & Francis Group, LLC
producing and excreting cyanide compounds (Chapter 3). Elevated concentrations of cyanide occur
288 Cyanide in Water and Soil
15.4.1 DATA QUALITY DETERMINATION
Reported data were screened according to the following criteria. In some instances, these cri-
teria could not be applied, and in some instances where data were accepted, qualifications were
identified.
• Primary publications were used when possible, rather than review papers.
• The complete study design had to be detailed in the paper.
• Multiple doses had to be tested with evidence of a satisfactory dose–response relationship.
• Studies had to report either a lethal dose for 50% of a population (LD50), or no observable
adverse effect level (NOAEL) calculated using an acceptable statistical method for each
endpoint measured.
15.4.2 DATA NORMALIZATION
Data were normalized from the units reported in the original study to dose in units of milligrams
[mg] of cyanide ion [CN] per kilogram [kg] body weight [BW] to facilitate comparison between
studies. The calculations performed are outlined below.
15.4.2.1 Normalization to mg/kg Body Weight
The concentration or doses of cyanide compound (CC) were converted to a standard dose of mg
tested compound (TC) per kg BW using the following equations:

• Dietary food concentration reported in ppm:
ppm (mg CC/kg food) ×average food consumption (kg food/day)
average body weight (kg BW)
= mg TC/kg BW/day
(15.1)
• Drinking water or injection concentration reported in mmol/kg:
mmol CC/kg ×(1 mol/1000 mmol) × molec. wt.(g/mol) × 1000 mg/g
= mg TC/kg BW (15.2)
In some subchronic and chronic tests, the doses tested changed during the study, requiring
an assumption about the average dose tested. For example, one study commenced with one-day-old
chicks and lasted for nine weeks, during which time the concentration of cyanide in the food remained
unchanged, but the ration consumed and, hence, dose changed with time [12]. Sample et al. [13]
proposed a solution for this situation in their derivation of widely-used toxicological benchmarks
for wildlife. They proposed using the animal’s average body weight for the test period to calculate
average food consumption using an accepted allometric equation from USEPA [14]:
food consumption rate (g/day) = 0.648(BW [g])
0.651
(15.3)
These values were expressed as kg food/day by multiplying by 0.001 g/kg. Sample et al. [13] note
that this method over- and under-estimates food consumption (and hence dose) for younger and older
chicks, respectively, but is an acceptable estimate of the average dose.
© 2006 by Taylor & Francis Group, LLC
Toxicity of Cyanide to Aquatic-Dependent Wildlife 289
TABLE 15.1
Cyanide Compounds Tested and Percentage Cyanide Contents Assumed
in Normalizing Doses to CN
Compound name Formula
Formula
weight
CN molecular

weight Percent CN
Acetone cyanohydrin C
4
H
7
NO 85.12 26.02 30.57
Acetonitrile C
2
H
3
N 41.06 26.02 63.37
Acrylonitrile C
3
H
3
N 53.07 26.02 49.03
CN of cassava NA NA 26.02 100
Hydrocyanic acid CHN 27.03 26.02 96.26
Malononitrile C
3
H
2
N
2
66.07 26.02 39.38
n-butyronitrile C
4
H
7
N 69.12 26.02 37.64

Potassium cyanide KCN 65.12 26.02 39.96
Propionitrile C
3
H
5
N 56.10 26.02 46.38
Sodium cyanide NaCN 49.01 26.02 53.09
Succinonitrile C
4
H
4
N
2
80.10 26.02 32.48
NA = not available.
15.4.2.2 Normalization of Toxic Dose to Cyanide Ion
After normalizing dosages based on total chemical concentrations, the data were normalized for CN
dose (mg CN/kg BW) by accounting for the percentage of cyanide in the test compound (Table 15.1).
Dosages normalized in these two manners were then compared.
15.4.2.3 Endpoint Normalization
The objective of this analysis was to express all test results in terms of NOAEL values normalized
to mg CN/kg BW. However, different studies reported toxicities in various ways, often hindering
comparison. The methodology used by the European Commission [15] was adopted; it estimates
NOAEL values by applying an uncertainty factor of 10 to the lowest observable adverse effect level
(LOAEL) for a chronic endpoint, and an uncertainty factor of 100 for an LD50. These assessment
factors are not well researched and are thus uncertain, especially for fast-acting gases like the free
and simple cyanide compounds, which appear to possess a single mode of action.
15.5 DATA ANALYSIS
Results are expressed as cumulative frequency distributions, which allowed interpretation of the data
in terms of:

• Relative sensitivity of birds versus mammals
• Relative toxicity of exposure routes
• No-effect levels protecting each organism group and exposure pathway
• Data variability
Normalized data for mammals exposed via drinking water (DW), food, and injection pathways
© 2006 by Taylor & Francis Group, LLC
are shown in Figure 15.1. Raw data are provided in Tables 15.2 to 15.4. Data for birds are shown
with the mammalian data in Figure 15.2, and raw data are listed in Tables 15.5 to 15.7.
290 Cyanide in Water and Soil
0.001 0.01 0.1 1 10 100
mg CN/kg BW
10
20
30
40
50
60
70
80
90
Cumulative percent
0
100
FIGURE 15.1 Toxicity of cyanide to mammals as a function of exposure pathway, with endpoints normalized
to NOAELs expressed as mg CN/kg BW (see text for details regarding normalization). Data are plotted using a
cumulative distribution function of the ranked NOAELs. Data points corresponding to specific cyanide exposure
pathways are denoted by (♦) for drinking water, () for food, and () for direct injection.
Normalized cyanide NOAELs ranged from 0.005 to 80 mg CN/kg BW. The lowest estimated
no-effect levels and, hence, the most sensitive endpoints were injection studies with mammals
(Figure 15.1). The latter exhibited no-effect concentrations ranging from 0.005 to 1.4 mg CN/kg

representing injection studies with complex cyanides fell into the upper portion of the dataset;
although the lowest NOAEL for a complex cyanide was 0.027 mg CN/kg BW, the majority of
NOAELs for complex cyanides were greater than 0.13 mg CN/kg BW (Table 15.4 and Figure 15.1).
Only one avian injection study was found with a NOAEL of 0.16 mg CN/kg BW based on mortality,
Dietary exposures of complex cyanides appeared much less toxic to birds and mammals than
those with simple cyanides. The estimated NOAELs for complex cyanides introduced via the diet
studies. The remaining avian food ingestion studies used sodium cyanide, which exhibited much
greater toxicity with estimated NOAELs ranging from 0.014 to 0.11 mg CN/kg BW (Table 15.6).
NOAELs estimated from drinking water studies for both birds and mammals fell within the
ranges of most other NOAELs except for mammalian food ingestion studies (Figure 15.2). Estimated
15.6 DISCUSSION
Data presented in the previous section will be discussed first in terms of the influence of exposure
route on the relative toxicity of cyanide to mammals and birds, and then in terms of differences
between mammals and birds for each exposure route.
15.6.1 ROUTE OF EXPOSURE —MAMMALS
Two studies examined effects of drinking water exposure to two different wildlife species from three
simple cyanide compounds [16,17]. Ballantyne’s [17] study with rabbits calculated very similar
© 2006 by Taylor & Francis Group, LLC
BW, although the majority (approximately 85%) was below 0.1 mg CN/kg BW (Table 15.4). Data
which ranks it within the upper range of estimated mammalian NOAELs (Table 15.7 and Figure 15.2).
ranged from 5.9 to 79.6 mg CN/kg BW (Table 15.3 and Figure 15.2), and included the single bird
food ingestion study with cassava (Table 15.6) along with all of the mammalian food ingestion
NOAELs for mammals ranged from 0.02 to 4.3 mg CN/kg BW (Table15.2), and those for birds ranged
from 0.01 to 0.8 mg CN/kg BW (Table 15.5).
Toxicity of Cyanide to Aquatic-Dependent Wildlife 291
TABLE 15.2
Toxicity of Cyanide to Mammals Exposed via Drinking Water
Reference Species
Age/
body

weight
Cyanide
compound
tested
Exposure
type Endpoint Effect
Concentration
as reported
Concentration
normalized to
NOAEL mg
compound/kg
BW
Concentration
normalized to
NOAEL mg
CN/kg BW Comments
[17] Oryctolagus cuniculus
(Rabbit)
Unknown/
unknown
KCN Water gavage Mortality LD50 0.09 mmol/kg 0.059 0.023 Study design not
described in
detail
[17] Oryctolagus cuniculus
(Rabbit)
Unknown/
unknown
HCN Water gavage Mortality LD50 0.092 mmol/kg
0.025 0.024 Study design not

described in
detail
[17] Oryctolagus cuniculus
(Rabbit)
Unknown/
unknown
NaCN Water gavage Mortality LD50 0.104 mmol/kg 0.051 0.027 Study design not
described in
detail
[17] Oryctolagus cuniculus
(Rabbit)
Unknown/
unknown
KCN Water gavage Mortality LD50 0.115 mmol/kg 0.075 0.030 Study design not
described in
detail
[17] Oryctolagus cuniculus
(Rabbit)
Unknown/
unknown
NaCN Water gavage Mortality LD50 0.117 mmol/kg 0.057 0.030 Study design not
described in
detail
[17] Oryctolagus cuniculus
(Rabbit)
Unknown/
unknown
HCN Water gavage Mortality LD50 0.156 mmol/kg
0.042 0.041 Study design not
described in

detail
[16] Canis latrans (Coyote) Unknown/
7to15kg
NaCN Water gavage Mortality NOAEL 4 mg/kg
4 2.124
[16] Canis latrans (Coyote) Unknown/
7to15kg
NaCN Water gavage Mortality LOAEL 8 mg/kg
8 4.247
© 2006 by Taylor & Francis Group, LLC
292 Cyanide in Water and Soil
TABLE 15.3
Toxicity of Cyanide to Mammals Exposed via Food Ingestion
Reference Species
Age/
body
weight
Cyanide
compound
tested
Exposure
type Endpoint Effect
Concentration
as reported
Concentration
normalized to
NOAEL mg
compound/kg
BW
Concentration

normalized to
NOAEL mg CN/kg
BW Comments
[19] Cricetomys gambianus
Waterhouse
Rat (African giant)
Weaning/
87 g
HCN Dietary
(concentration
in cassava
parts)
Growth rate NOAEL 110 mg/kg*
food
6 5.917 HCN
measured in
cassava
tuber
[18] Sus sp. (Pig) Unknown
16.1 kg
CN of
cassava
Dietary Mortality Unbounded
NOAEL
400 ppm 17.25 17.250
[18] Sus sp. (Pig) Unknown/
16.1 kg
CN of
cassava
Dietary Daily weight

gain
Unbounded
NOAEL
400 ppm 17.25 17.250
[19] Cricetomys gambianus
Waterhouse
Rat (African giant)
Weaning/
87 g
HCN Dietary
(concentration
in cassava
parts)
Mortality Unbounded
NOAEL
597 mg/kg*
food
33 32.236 HCN
measured in
cassava peel
[32] Canis familiaris (Dog) Unknown/
unknown
NaCN Dietary Food
consumption,
blood
chemistry,
behavior, or
organ
histology
NOAEL 150 mg/kg 150 79.635 As cited by

[6]
[19] Cricetomys gambianus
Waterhouse
Rat (African giant)
Weaning/
87 g
HCN Dietary
(concentration
in cassava
parts)
Growth rate LOAEL 150 mg/kg*
food
8 8.068 HCN
measured in
cassava
tuber
© 2006 by Taylor & Francis Group, LLC
Toxicity of Cyanide to Aquatic-Dependent Wildlife 293
TABLE 15.4
Toxicity of Cyanide to Mammals Exposed via Direct Injection
Reference Species
Age/
body
weight
Cyanide
compound
tested
Exposure
type Endpoint Effect
Concentration

as reported
Concentration
normalized to
NOAEL mg
compound/kg
BW
Concentration
normalized to
NOAEL mg CN/kg
BW Comments
[17] Oryctolagus cuniculus
(Rabbit)
Unknown/
unknown
HCN Intramuscular Mortality LD50 0.018 mmol/kg
0.005 0.005 Female value used,
male not
significantly
different. Study
design not
described in detail
[17] Oryctolagus cuniculus
(Rabbit)
Unknown/
unknown
HCN Intravenous Mortality LD50 0.022 mmol/kg 0.006 0.006 Study design not
described in detail
[21] Oryctolagus cuniculus
(Rabbit)
Unknown/

unknown
HCN IV injection Mortality LD50 0.66 mg/kg
0.007 0.006
[17] Oryctolagus cuniculus
(Rabbit)
Unknown/
unknown
NaCN Intravenous Mortality LD50 0.025 mmol/kg
0.012 0.007 Study design not
described in detail
[17] Oryctolagus cuniculus
(Rabbit)
Unknown/
unknown
KCN Intravenous Mortality LD50 0.029 mmol/kg
0.019 0.008 Study design not
described in detail
[21] Felis catus (Cat) Unknown/
unknown
HCN IV injection Mortality LD50 0.81 mg/kg 0.008 0.008
[21] Rattus norvegicus (Rat) Unknown/
unknown
HCN IV injection Mortality LD50 0.81 mg/kg
0.008 0.008
[17] Oryctolagus cuniculus
(Rabbit)
Unknown/
unknown
NaCN Intramuscular Mortality LD50 0.033 mmol/kg 0.016 0.009 Male value used,
female not

significantly
different. Study
design not
described in detail
© 2006 by Taylor & Francis Group, LLC
294 Cyanide in Water and Soil
TABLE 15.4
Continued
Reference Species
Age/
body
weight
Cyanide
compound
tested
Exposure
Type Endpoint Effect
Concentration
as reported
Concentration
normalized to
NOAEL mg
compound/kg
BW
Concentration
normalized to
NOAEL mg CN/kg
BW Comments
[21] Mus musculus (Mouse) Unknown/
unknown

HCN IV injection Mortality LD50 0.99 mg/kg
0.010 0.010
[17] Oryctolagus cuniculus
(Rabbit)
Unknown/
unknown
HCN Transocular
injection
Mortality LD50 0.039 mmol/kg 0.010 0.010 Study design not
described in detail
[17] Oryctolagus cuniculus
(Rabbit)
Unknown/
unknown
KCN Intramuscular Mortality LD50 0.047 mmol/kg
0.031 0.012 Male value used,
female not
significantly
different. Study
design not described
in detail
[21] Macaca mulatta (Monkey) Unknown/
unknown
HCN IV injection Mortality LD50 1.3 mg/kg
0.013 0.013
[21] Canis familiaris (Dog) Unknown/
unknown
HCN IV injection Mortality LD50 1.34 mg/kg
0.013 0.013
[21] Cavia porcellus (Guinea Pig) Unknown/

unknown
HCN IV injection Mortality LD50 1.43 mg/kg
0.014 0.014
[17] Oryctolagus cuniculus
(Rabbit)
Unknown/
unknown
KCN IP injection Mortality LD50 0.055 mmol/kg
0.036 0.014 Study design not
described in detail
[17] Oryctolagus cuniculus
(Rabbit)
Unknown/
unknown
NaCN IP injection Mortality LD50 0.057 mmol/kg
0.028 0.015 Female value used,
male not
significantly
different. Study
design not described
in detail
© 2006 by Taylor & Francis Group, LLC
Toxicity of Cyanide to Aquatic-Dependent Wildlife 295
[17] Oryctolagus cuniculus
(Rabbit)
Unknown/
unknown
HCN IP injection Mortality LD50 0.064 mmol/kg 0.017 0.017 Male value used,
female not
significantly

different. Study
design not
described in
detail
[17] Rattus norvegicus (Rat) Unknown/
unknown
HCN IP injection Mortality LD50 0.083 mmol/kg 0.022 0.022 Male value used,
female not
significantly
different. Study
design not
described in
detail
[17] Rattus norvegicus (Rat) Unknown/
unknown
KCN IP injection Mortality LD50 0.085 mmol/kg 0.055 0.022 Study design not
described in
detail
[33] Rattus norvegicus (Rat)
(Sprague–Dawley)
Unknown/ 250
to 260 g
KCN IP injection Mortality LD50 0.088 mmol/kg 0.057 0.023
[17] Mus musculus (Mouse) Unknown/
unknown
NaCN IP injection Mortality LD50 0.093 mmol/kg 0.046 0.024 Study design not
described in
detail
[17] Rattus norvegicus (Rat) Unknown/
unknown

NaCN IP injection Mortality LD50 0.096 mmol/kg 0.047 0.025 Study design not
described in
detail
[17] Cavia porcellus (Guinea Pig) Unknown/
unknown
HCN IP injection Mortality LD50 0.098 mmol/kg 0.027 0.025 Study design not
described in
detail
[17] Mus musculus (Mouse) Unknown/
unknown
KCN IP injection Mortality LD50 0.099 mmol/kg 0.065 0.026 Study design not
described in
detail
[17] Cavia porcellus (Guinea Pig) Unknown/
unknown
KCN IP injection Mortality LD50 0.1 mmol/kg 0.065 0.026 Study design not
described in
detail
[22] Mus musculus (CD-1 mouse) Unknown/
30 g
Acetone
cyanohydrin
IP injection Mortality LD50 8.7 mg/kg 0.087
0.027
© 2006 by Taylor & Francis Group, LLC
296 Cyanide in Water and Soil
TABLE 15.4
Continued
Reference Species
Age/

body
weight
Cyanide
compound
tested
Exposure
type Endpoint Effect
Concentration
as reported
Concentration
normalized to
NOAEL mg
compound/kg
BW
Concentration
normalized to
NOAEL mg CN/kg
BW Comments
[17] Mus musculus (Mouse) Unknown/
unknown
HCN IP injection Mortality LD50 0.103 mmol/kg
0.028 0.027 Study design not
described in
detail
[17] Oryctolagus cuniculus
(Rabbit)
Unknown/
unknown
NaCN Transocular
injection

Mortality LD50 0.103 mmol/kg 0.050 0.027 Study design not
described in
detail
[34] Canis familiaris (Dog) Unknown/
unknown
NaCN Subcutaneous
injection
Mortality LD50 5.36 mg/kg 0.054 0.028 As reported by
[16]
[17] Cavia porcellus (Guinea Pig) Unknown/
unknown
NaCN IP injection Mortality LD50 0.112 mmol/kg
0.055 0.029 Study design not
described in
detail
[17] Oryctolagus cuniculus
(Rabbit)
Unknown/
unknown
KCN Transocular
injection
Mortality LD50 0.121 mmol/kg 0.079 0.031 Study design not
described in
detail
[17] Oryctolagus cuniculus
(Rabbit)
Unknown/
unknown
HCN Percutaneous
injection

Mortality LD50 0.26 mmol/kg 0.071 0.068 Study design not
described in
detail
[22] Mus musculus (CD-1 mouse) Unknown/
30 g
Malononitrile IP injection Mortality LD50 18 mg/kg
0.18 0.071
[17] Oryctolagus cuniculus
(Rabbit)
Unknown/
unknown
NaCN Percutaneous
injection
Mortality LD50 0.298 mmol/kg 0.146 0.078 Study design not
described in
detail
[17] Oryctolagus cuniculus
(Rabbit)
Unknown/
unknown
KCN Percutaneous
injection
Mortality LD50 0.343 mmol/kg 0.223 0.089 Study design not
described in
detail
© 2006 by Taylor & Francis Group, LLC
Toxicity of Cyanide to Aquatic-Dependent Wildlife 297
[22] Mus musculus (CD-1 mouse) Unknown/
30 g
Propionitrile IP injection Mortality LD50 28 mg/kg 0.28 0.130

[22] Mus musculus (CD-1 mouse) Unknown/
30 g
n-Butyronitrile IP injection Mortality LD50 38 mg/kg
0.38 0.143
[22] Mus musculus (CD-1 mouse) Unknown/
30 g
Succinonitrile IP injection Mortality LD50 62 mg/kg 0.62 0.201
[22] Mus musculus (CD-1 mouse) Unknown/
30 g
Acrylonitrile IP injection Mortality LD50 46 mg/kg 0.46 0.226
[20] Rattus norvegicus (Rat)
(Wistar)
Adult/ 275 to
325 g
KCN Injection Mortality NOAEL 2.5 mg/kg BW 2.5 0.999
[22] Mus musculus (CD-1 mouse) Unknown/
30 g
Acetonitrile IP injection Mortality LD50 175 mg/kg 1.75 1.109
[20] Rattus norvegicus (Rat)
(Wistar)
Adult/ 275 to
325 g
KCN Injection Mortality LOAEL 3.5 mg/kg BW 3.5 1.398
© 2006 by Taylor & Francis Group, LLC
298 Cyanide in Water and Soil
0.001 0.01 0.1 1 10 100
mg CN/kg BW
20
30
40

50
60
70
80
90
10
Cumulative percent
100
0
FIGURE 15.2 Toxicity of cyanide to birds and mammals as a function of exposure pathway, with endpoints
normalized to NOAELs expressed as mg CN/kg BW (see text for details regarding normalization). Data are
plotted using a cumulative distribution function of the ranked NOAELs. Data points corresponding to specific
organisms and cyanide exposure pathwaysaredenotedby() for mammals by drinking water, () for mammals
by food, () for mammals by direct injection, () for birds by drinking water, (•) for birds by food, and ()
for birds by direct injection.
LD50s for drinking water exposure of HCN, NaCN, and KCN: estimated NOAELs ranged from
and LOAEL for mortality (2.1 and 4.2 mg CN/ kg BW, respectively), that overlapped the LD50 range
for rabbits (LD50s of 2.3 to 4.1 mg CN/kg BW). However, the coyote NOAEL was 100 times higher
than the rabbit NOAELs (Table 15.2).
None of the three studies that examined cyanide toxicity via ingestion [6,18,19] indicated that
complex cyanides in food were as toxic as simple cyanides in drinking water or administered by
injection. Tewe and Pessu [18] fed pigs a diet of cassava for 72 days that contained up to 400 ppm
cyanide, including both free and bound cyanide with additional KCN added. Because the pigs
grew significantly during the study period, the methods of Sample et al. [13] were used to estimate
the average dose tested. The average weight of the pigs was 32 kg, and the food consumption
given in the paper (i.e., 1.38 kg food/day) was used to calculate a dose of 17.25 mg CN/kg BW
test concentrations compared to the control animal responses. Tewe’s [19] study, with African giant
rats fed various parts of cassava containing differing cyanide concentrations (0, 110, 150, 597 mg
HCN/kg cassava) for 16 weeks, disclosed no mortality at the highest concentration (597 mg HCN/kg
cassava, or 32 mg CN/kg BW; Table 15.3), but reduced growth rate was observed at the mid and

highest concentration (NOAEL of 5.9 mg CN/kg BW and LOAEL of 8.1 mg CN/kg BW). There was
a discrepancy in the paper regarding the cyanide concentration units; the tables in the text reported
mg/g, but the abstract and Eisler [6] reported them in mg/kg. As mg/kg was used in another Tewe
study of cyanide concentrations in cassava [18], we assumed mg/kg to be the correct units. One
other study reported by Eisler [6] investigated the effects of 30 days cyanide food ingestion by dogs.
No sublethal effects on food ingestion were observed at 80 mg CN/kg BW, which was assumed to
represent the NOAEL (Table 15.3).
The greatest number of studies and endpoints of cyanide toxicity to mammals represented
LD50s arising from injected doses. Ballantyne [17] studied four species (rat, mouse, rabbit, guinea
pig), five different injection routes (intravenous, intramuscular, intraperitoneal, percutaneous, and
transocular), and three simple cyanide compounds (HCN, NaCN, and KCN). This study observed
LD50s ranging from 0.5 to 9 mg CN/kg BW (estimated NOAELs of 0.005 to 0.089 mg CN/kg BW;
© 2006 by Taylor & Francis Group, LLC
0.023 to 0.041 mg CN/kg BW (Table 15.2). Sterner’s [16] study with coyotes observed a NOAEL
(Table 15.3). No significant mortality or weight gain differences were observed at these highest
Table 15.4).
Toxicity of Cyanide to Aquatic-Dependent Wildlife 299
TABLE 15.5
Toxicity of Cyanide to Birds Exposed via Drinking Water
Reference Species
Age/
body
weight
Cyanide
compound
tested
Exposure
type Endpoint Effect
Concentration
as reported

Concentration
normalized to
NOAEL mg
compound/kg
BW
Concentration
normalized to
NOAEL mg CN/kg
BW
[23] Anas platyrhynchos
(Mallard)
Young adult
females/1000 g
KCN Water
gavage
Liver and
brain ATP
levels
Unbounded
LOAEL
0.25 mg/kg 0.025 0.010
[23] Anas platyrhynchos
(Mallard)
Young adult
females/1000 g
KCN Water
gavage
Mortality Unbounded
NOAEL
2 mg/kg 2 0.799

[23] Anas platyrhynchos
(Mallard)
Young adult
females/
1000 g
KCN Water
gavage
Heart ATP
levels
Unbounded
NOAEL
mg/kg 2 0.799
© 2006 by Taylor & Francis Group, LLC
300 Cyanide in Water and Soil
TABLE 15.6
Toxicity of Cyanide to Birds Exposed via Food Ingestion
Reference Species
Age/
body
weight
Cyanide
compound
tested
Exposure
type Endpoint Effect
Concentration
as reported
Concentration
normalized to
NOAEL mg

compound/kg
BW
Concentration
normalized to
NOAEL mg CN/kg
BW Comments
[25] Anas platyrhynchos
(Mallard)
6-month old/
1260 g
NaCN Gelatin capsule Mortality LD50 2.7 mg/kg 0.027 0.014
[24] Falco sparverius
(American kestrel)
Unknown/
118 g
NaCN Gelatin capsule Mortality LD50 4 mg/kg 0.04 0.021 Good study with
different species,
no control birds
reported
[24] Coragyps atratus
(Black vulture)
Unknown/
2215 g
NaCN Gelatin capsule Mortality LD50 4.8 mg/kg 0.048 0.025 Good study with
different species,
no control birds
reported
[24] Otus asio
(Eastern screech-
owl)

Unknown/
185 g
NaCN Gelatin capsule Mortality LD50 8.6 mg/kg 0.086 0.046 Good study with
different species,
no control birds
reported
[24] Coturnix japonica
(Japanese quail)
Reproductively
active/130 g
NaCN Gelatin capsule Mortality LD50 9.4 mg/kg 0.094 0.050 Good study with
different species,
no control birds
reported, value
used with male
and female data
combined
© 2006 by Taylor & Francis Group, LLC
Toxicity of Cyanide to Aquatic-Dependent Wildlife 301
[24] Sturnus vulgaris
(Starling)
Unknown/
75 g
NaCN Gelatin capsule Mortality LD50 17 mg/kg 0.17 0.090 Good study with
different
species, no
control birds
reported, value
used with male
and female data

combined
[24] Gallus domesticus
(Chicken)
Unknown/
1610 g
NaCN Gelatin capsule Mortality LD50 21 mg/kg 0.21 0.111 Good study with
different
species, no
control birds
reported
[12] Gallus domesticus
(Chick (Broiler))
1 day/ 32 g CN of cassava Dietary
(concentration in
cassava added to
food)
Mortality Unbounded
NOAEL
83 ppm 6.024 6.024 Cassava added to
food, difficult to
calculate dose.
Average BW
used in EPA
food
consumption
equation for
birds = 38.47 g
food/day
© 2006 by Taylor & Francis Group, LLC
302 Cyanide in Water and Soil

TABLE 15.7
Toxicity of Cyanide to Birds Exposed via Direct Injection
Reference Species
Age/
body
weight
Cyanide
compound
tested
Exposure
type Endpoint Effect
Concentration
as reported
Concentration
normalized to
NOAEL mg
compound/kg
BW
Concentration
normalized to
NOAEL mg CN/kg
BW Comments
[26] Columba livia
(Rock Dove)
KCN IV or
intramuscular
injection
Mortality LOAEL 4 mg/kg 0.4 0.160 As reported by [24]
© 2006 by Taylor & Francis Group, LLC
Toxicity of Cyanide to Aquatic-Dependent Wildlife 303

Our review suggested that cyanide’s toxicity is remarkably similar when simple cyanide
compounds were injected. Most of the estimated NOAELs (83%) ranged between 0.005 and
LOAEL for lethality to be 1 and 1.4 mg CN/kg BW, respectively. They also measured various energy
metabolites in the brain and found that all returned to control levels within 6 to 24 h after the initial
adverse effect. McNamara [21] injected HCN into seven different mammals and derived LD50s
ranging from 0.6 to 1.4 mg CN/kg BW (estimated NOAELs of 0.006 and 0.014 mg CN/kg BW).
Complex organic cyanides are less toxic than simple cyanides when injected into mammals.
Willhite and Smith [22] investigated toxicity to rats of seven aliphatic nitriles (organic chemicals
with the general formula of R–CN). Five of the seven compounds had the least toxic LD50s of
all injection studies (13 to 110 mg CN/kg BW, estimated NOAELs of 0.13 to 1.1 mg CN/kg BW)
(Figure 15.1, Table 15.4). There was one exception: the estimated NOAEL for acetone cyanohydrin
(0.027 mg CN/kg BW) fell within the upper range of the mammalian injection data.
The injection study endpoints (mostly estimated from LD50s) overlap the drinking water
NOAELs, while food consumption NOAELs are greater (i.e., less toxic) than the other routes of
exposure (Figure 15.1). A trend of increased tolerance, increased metabolism, and reduced bioavail-
ability can be seen proceeding from the injection to water ingestion to dietary exposure pathways.
However, this generalization should be viewed with caution owing to the paucity of food ingestion
and drinking water data compared to injection data.
15.6.2 ROUTE OF EXPOSURE —BIRDS
The avian drinking water data were obtained from a single study, and the results fall within the toxicity
range reported for mammals exposed via drinking water. Young adult female mallards were dosed
with a single gavage of potassium cyanide, and mortality and ATP concentrations were measured
in the liver, brain, and heart [23]. A significant decrease in liver and brain ATP concentrations was
observed at the lowest dose (0.1 mg CN/kg BW, estimated NOAEL of 0.01 mg CN/kg BW), with no
significant effect on heart ATP concentrations or mortality at the highest dose (0.8 mg CN/kg BW)
Three studies investigated aviantoxicityvia food ingestion, and most NOAELs were considerably
studies with single gelatin capsules given to the birds to derive LD50 values [24,25], and one 9-week
study with cassava added to food [12]. The study by Henny et al. [25] used 6-week old mallards, while
the age of the birds in the Wiemeyer et al. [24] study was not reported. However, the LD50 values
were within an order of magnitude (0.027 to 0.21 mg CN/kg BW, estimated NOAELs from 0.014

to 0.11 mg CN/kg BW) for the seven different species when only simple cyanide exposures were
fed complex cyanides in the form of cassava. This long-term study by Gomez et al. [12] started
with one-day-old chicks fed cassava-amended feed for nine weeks. They observed no mortality with
feed containing the highest dose of 83 mg CN/kg food. However, because body weight and food
consumption were not reported daily and changed over time, the dose was estimated by the methods
described in Section 15.4.2.1. Accordingly, the four-week body weight was calculated to be 530 g and
food consumption was calculated to be 38.5 g food/day. The latter value might be slightly less than
the birds were actually consuming, as the average consumption for the first four weeks was reported
in the paper as 36.8 g/day and 101 g/day for the next five weeks. Because this unbounded
4
NOAEL
(6.02 mg CN/kg BW) falls in the range of the LD50s for the other birds (Figure 15.2, Table 15.6),
4
Unbounded refers to NOAELs that are not accompanied by an estimate of the corresponding LOAEL, or LOAELs
unaccompanied by the NOAEL. The true values of NOAELs estimated using unbounded LOAELs are more uncertain
than bounded values.
© 2006 by Taylor & Francis Group, LLC
0.1 mg CN/kg BW (Figure 15.1). The rest ranged between 0.1 and 1.1 mg CN/kg BW (Figure 15.1,
lower than those reported for mammals exposed via diet (Figure 15.2). These included two acute
Table 15.4). For example, MacMillan [20] injected KCN into mice and observed a NOAEL and
(Table 15.5). All ATP concentrations returned to normal by 24 h postexposure.
considered (Figure 15.2, Table 15.6). In contrast, dietary cyanide was much less toxic to birds when
304 Cyanide in Water and Soil
it can be inferred that the cyanide found in the cassava remains bound in the gastrointestinal tract and
has limited bioavailability. This is consistent with mammalian data as discussed in the next section.
To illustrate the variability inherent in the exposure equations, the use of the lowest body weight and
calculated food ingestion rate produced an unbounded NOAEL of 16 mg CN/kg BW (versus 6.02
based on the average).
The only studies available concerning birds dosed via direct injection were not available for direct
review, and so we relied on secondary citations. One study [26] reported by Wiemeyer et al. [24]

identified the minimum lethal dose of KCN injected into rock doves as being 4 mg/kg (1.6 mg CN/kg
BW). This was assumed to be a LOAEL, which was divided by 10 to estimate the NOAEL of
Overall, the estimated NOAELs for birds exposed via all exposure pathways ranged from 0.01
with the lowest being a NOAEL for drinking water reporting no effect on liver and brain ATP
concentrations. A consistent trend in the data is the small range of LD50 values reported in the
Wiemeyer et al. [24] study of different bird species exposed via diet to sodium cyanide. These LD50s
ranged from 2.7 to 21 mg NaCN/kg BW (estimated NOAELs of 0.014 to 0.11 mg CN/kg BW).
15.6.3 COMPARISONS BETWEEN BIRDS AND MAMMALS
15.6.3.1 Drinking Water
Differences in sensitivity between birds and mammals exposed to cyanide in drinking water are
difficult to ascertain from the data analyzed here, as all bird NOAELs and LOAELs were unbounded
and, hence, more uncertain than bounded values. Also, the majority of mammalian data wasestimated
from LD50s and, hence, used the uncertain 100-fold assessment factor. Nevertheless, these data
suggest that sublethal effects to birds and mammals occur at similar cyanide concentrations. For
mammals, the majority of the estimated NOAELs ranged from 0.02 to 0.04 mg CN/kg BW and for
birds from 0.01 to 0.8 mg CN/kg BW (Figure 15.2).
15.6.3.2 Food
Greater differences were observed between birds and mammals in terms of dietary cyanide toxicity,
with birds possibly being more sensitive. Avian NOAELs for simple cyanides ranged from 0.014
to 0.11 mg CN/kg BW, and those for mammals were higher (Figure 15.2). In one case, however,
sensitivities appeared similar. A NOAEL from the single chronic avian study, which used feed
amended with cassava (6.0 mg CN/kg BW for mortality based on a calculated exposure using median
15.6.3.3 Direct Injection
Because only one bird injection study was identified, few conclusions can be drawn concerning the
relative sensitivity of birds and mammals to cyanide via injection. The single avian study fell within
the least sensitive 10 to 20% of mammal tests reported (Figure 15.2).
15.6.4 SIMPLE CYANIDE VERSUS COMPLEX CYANIDE COMPOUNDS
Compared to injection studies with simple cyanide compounds (HCN, KCN, NaCN), the majority
of the estimated mammalian NOAELs for complex cyanides were 5 to 100 times higher. The study
with complex cyanides used aliphatic nitriles [22]. Presumably, cyanide in these compounds may be

bound more tightly and, hence, dissociate less readily to HCN than the simple cyanide compounds.
Nitrile complexes are known to be comparatively innocuous in the environment, low in chemical
reactivity, and biodegradable [6].
© 2006 by Taylor & Francis Group, LLC
to 6 mg CN/kg BW (Figure 15.2). Toxicity data for all exposure routes were within the same range,
0.16 mg CN/kg BW (Table 15.7).
weight and food ingestion; Table 15.6) was similar to the lowest NOAEL for mammals fed cassava
(5.9 mg CN/kg BW; Table 15.3).
Toxicity of Cyanide to Aquatic-Dependent Wildlife 305
the toxicities of cyanide to birds and mammals from food amended with a simple cyanide versus
complex cyanide compounds (i.e., cassava). Most of the cyanide found in cassava is part of a larger
molecule that Tewe [19] and Eisler [6] refer to as cyanogenic glucoside. Its toxicity is likely due to the
enzymatic release of HCN [6], but the rate of release of free cyanide from the cyanogenic glucosides
has not been reported. Comparing the two bird studies, the unbounded NOAEL for mortality of birds
consuming cassava for an extended period of time was about 50 times higher (i.e., less toxic) than the
suggests simple cyanides are more toxic, the available mammalian data do not confirm this. In the
mammalian studies, the NOAEL for a study of a simple cyanide compound was more than twice that
of cyanide in cassava. A possible explanation for the apparent contradiction in these results may be
differential volatilization of HCN from the cassava feed owing to different methods of preparation,
or different amounts of feed not immediately consumed.
15.7 BIOACCUMULATION OF CYANIDE
Acute toxicity is the principal hazard posed by cyanide poisoning in wildlife. Cyanide does not
bioaccumulate in animals [1] because sublethal doses are rapidly metabolized and excreted [10].
Therefore, sublethal effects are short-lived if present at all. In addition, cyanide does not appear
to be persistent in the environment. Cyanides are lost from the water column due to precipitation
are usually complexed by trace metals, precipitated, metabolized by microorganisms, or volatilized
(e.g., eagles, osprey, mink) consuming aquatic animals exposedto cyanide are expected to be minimal
15.8 TOXICITY THRESHOLDS FOR CYANIDE
Eisler’s [6] review of cyanide toxicity data suggested that free cyanide concentrations of
<100 mg CN/kg diet for birds and <1000 mg CN/kg diet fresh weight for mammals would be

protective of those organisms. The avian threshold was based on two dietary studies [12,27], and
two drinking water studies [28,29]. The data of Gomez et al. [12] are at the high end (lesser toxicity)
of the rest of the estimated doses for birds. It is possible that the cyanide in cassava used in the
Gomez et al. [12] study was less bioavailable than the cyanide compounds used in the other avian
food studies, resulting in an estimated safe concentration that may be too high for birds exposed to
simple or free cyanide compounds. The original papers of Allen [28] and Clark and Hothem [29]
were not readily available and thus were not reviewed. However, review of these works by Eisler [6]
indicates that they suggested that <50 mg/l total cyanide would be safe for waterfowl when exposed
via drinking water.
One avian drinking water study, dosed young adult female mallards with a single gavage of
potassium cyanide, and measured mortality, and liver, brain, and heart ATP concentrations [23], as
discussed previously. The researchers found a significant decrease in liver and brain ATP concentra-
tions at the lowest dose given (0.1 mg CN/kg BW, estimated NOAEL of 0.01 mg CN/kg BW), and no
significant effect on heart ATP concentrations, or mortality at the highest dose (0.8 mg CN/kg BW).
However, all ATP concentrations returned to normal by 24 h postexposure. This suggests that there
may be short-term sublethal effects to birds at concentrations less than 50 mg/l total cyanide.
Eisler’s [6] mammalian threshold of <1000 mg/kg food fresh weight is based on one study [30]
with 1000 mg KCN/kg food added to the diet of weaning African giant rats (Cricetomys gambianus)
for 12 weeks. This study wasnot included in our analysis because it examinedonlyone dose. Eisler [6]
reported that Tewe observed reduced food intake and body weight at this one concentration. Another
study by Tewe [19] examined effects on giant rats fed cyanide-amended cassava. This study reported
© 2006 by Taylor & Francis Group, LLC
In contrast to the injection studies, no clear differences were apparent (Figure 15.2) between
NOAELs for birds acutely exposed to gelatin capsules containing NaCN (Table 15.6). Although this
and sedimentation, microbial degradation, and volatilization [6; and Chapter 9]. In soils, cyanides
[6; and Chapter 10]. Because cyanide does not bioaccumulate and is not persistent, risks to wildlife
(Chapter 17).
306 Cyanide in Water and Soil
a NOAEL and LOAEL based on a body weight endpoint at 110 and 150 mg/kg food, significantly
lower than the 1000 mg/kg food value used by Eisler [6]. No mortality was reported for cassava with

HCN added at 600 mg/kg food. Therefore, the 1000 mg/kg value proposed by Eisler [6] may be too
high to protect all mammals from the effects of dietary cyanide exposure.
From our review, doses of less than 0.01 mg CN/kg BW would be fully protective of birds and
mammals exposedtocyanide via both drinking waterandfood. While this is orders of magnitudemore
conservative than the 1000 mg/kg threshold suggested by Eisler [6], athresholdof0.01mgCN/kgBW
includes both water and dietary exposure pathways, and is consistent with sensitivity distributions
also suggest that this threshold — when converted to equivalent aqueous concentrations (µg CN/l)
using allometric equations — is also consistent with AWQC for protection of aquatic organisms [31].
Given that all vertebrate organisms share the same mode of action for acute cyanide mortality [1,6],
consistent toxicity thresholds from aqueous exposure are to be expected, and help confirm our more
conservative tissue threshold (0.01 mg CN/kg BW) for protection of aquatic-dependent wildlife.
15.9 SUMMARY AND CONCLUSIONS
• Estimated NOAELs for cyanide in animals range from 0.005 to 80 mg CN/kg BW for birds
and mammals exposed to all cyanide compounds via food, drinking water, and injection.
• Injection studies with mammals were the most sensitive with reported NOAELs ranging
from 0.005 to 1.1 mg CN/kg BW; however, the majority (about 85%) was below 0.1 mg
CN/kg BW. Data points from injection studies with complex cyanides were less sensitive,
with the majority of values exceeding 0.13 mg CN/kg BW.
• Both birds and mammals exhibit similar toxicity to cyanide when exposed via drinking
water; NOAELs for mammals range from 0.02 to 2.1 mg CN/kg BW, and NOAELs for
birds range from 0.01 to 0.8 mg CN/kg BW. These values overlap strongly with injection-
based NOAELs, suggesting a consistent toxicity of simple cyanides regardless of exposure
pathway.
• The highest (least toxic) estimated NOAELs range from 6 to 80 mg CN/kg BW, from a
single study of birds fed complex cyanides contained in food (cassava), and from all of the
mammal food cyanide ingestion studies with complex cyanides. Presumably, the complex
cyanide compounds dissociate less to HCN than the simple cyanide compounds.
• Acute toxicity appears to be the principal hazard posed by cyanide poisoning in wildlife.
Cyanide does not appear to bioaccumulate in animals because sublethal doses are rapidly
metabolized and excreted. Because cyanide does not bioaccumulate, effects to wildlife

(e.g., eagles, osprey, mink) consuming aquatic animals exposed to cyanide are projected
to be insignificant.
• From our review, doses of less than 0.01 mg CN/kg BW are expected to be protective
of birds and mammals exposed to cyanide via drinking water and food. While this is
conservative, a threshold of 0.01 mg CN/kg BW protects from both water and dietary
exposure pathways, and is consistent with sensitivity distributions for the most toxic simple
cyanides regardless of exposure pathway.
ACKNOWLEDGMENTS
This review was conducted in part with support from the Water Environment Research Foundation
(WERF), Project #01-ECO-1. We thank the WERF project coordinator, Margaret Stewart, and the
project subcommittee (Walter Berry, Phillip Dorn, Joseph Gorsuch, Jim Pletl, and Mary Reiley)
© 2006 by Taylor & Francis Group, LLC
for the most toxic simple cyanides regardless of exposure pathway (Figure 15.2). Ongoing studies
Toxicity of Cyanide to Aquatic-Dependent Wildlife 307
for their review of the manuscript. We also thank Joe Volosin for assistance with graphics, and Diane
Gensemer for proofreading and copyediting.
REFERENCES
1. USEPA, Ambient water quality criteria for cyanide — 1984, Report EPA 440/5-84-028, U.S.
Environmental Protection Agency, Washington, DC, 1985.
2. Kavanaugh, M.C., Deeb, R.A., Markowitz, D., Dzombak, D.A., Zheng, A., Theis, T.L., Young, T.C.,
and Luthy, R.G., Cyanide formation and fate in complex effluents and its relation to water quality criteria,
Report 98-HHE-5, Water Environment Research Foundation, Alexandria, VA, 2003.
3. Gensemer, R.W., DeForest, D., Coyner, A., Clark, J., Cardwell, R.D., Dzombak, D.A., Higgins, C., and
Santore, R.C., Reassessment of cyanide criteria for the protection of aquatic life and wildlife: phase I
annual progress report (01-ECO-1), Water Environment Research Foundation, Alexandria, VA, 2003.
4. Newman, M.C. and Jagoe, C.H., Ligands and the bioavailability of metals in aquatic environments,
in Bioavailability: Physical, Chemical, and Biological Interactions, Hammelink, J.L., Landrum, P.F.,
Bergman, H.L., and Benson, W.H., Eds., Lewis Publishers, Boca Raton, FL, 1994, p. 39.
5. USEPA, Screening level ecological risk assessment protocol for hazardous waste combustion facilities,
Report EPA 530-D-99-001A, U.S. Environmental Protection Agency, Washington, DC, 1999.

6. Eisler, R., Cyanide hazards to fish, wildlife, and invertebrates: a synoptic review, Biological Report
85(1.23), U.S. Fish and Wildlife Service, Washington, DC, 1991, p. 55.
7. Eisler, R., Clark, D.R., Wiemeyer, S.N., and Henny, C.J., Sodium cyanide hazards to fish and other
wildlife from gold mining operations, in Environmental Impacts of Mining Activities: Emphasis on
Mitigation and Remedial Measures, Azcue, J.M., Ed., Springer-Verlag, Berlin, 1999, p. 55.
8. Doudoroff, P., Leduc, G., and Schneider, C.R., Acute toxicity to fish of solutions containing complex
metal cyanides, in relation to concentrations of molecular hydrocyanic acid, T. Am. Fish. Soc., 95, 6,
1966.
9. Doudoroff, P., Toxicity to fish of cyanides and related compounds, Report EPA-600/3-76-038, U.S.
Environmental Protection Agency, Cincinnati, OH, 1976.
10. Hill, E.F. and Henry, P.F.P., Cyanide, in Noninfectious Diseases in Wildlife, Hoff, G.L., Ed., Iowa State
University Press, Ames, Iowa, 1996, p. 99.
11. Padmaja, G., The culprit in cassava toxicity: cyanogens or low protein?, Consultative Group on
12. Gomez, G., Aparico, M.A., and Willhite, C.C., Relationship between dietary cassava cyanide levels and
broiler performance, Nutr. Rep. Int., 37, 63, 1988.
13. Sample, B.E., Opresko, D.M., and Suter II, G.W., Toxicological benchmarks for wildlife: 1996 revi-
sion, Report ES/ER/TM-86/R3, U.S. Department of Energy, Office of Environmental Management,
Oak Ridge, TN, 1996.
14. USEPA, Wildlife exposure factorshandbook, Report EPA/600/R-93/187, U.S. Environmental Protection
Agency, Office of Research and Development, Washington DC, 1993.
15. European Commission, Technical guidance document in support of commission directive 93/67/EEC on
risk assessment for new notified substances and commission regulation (EC) No. 1488/94 on risk assess-
ment for existing substances, Office of Official Publication of the European Communities, Brussels,
Luxembourg, 1996.
16. Sterner, W.S., Effects of sodium cyanide and diphacinone in coyotes (Canis latrans): applications as
predacides in livestock toxic collars., B. Environ. Contam. Tox., 23, 211, 1979.
17. Ballantyne, B., The influence of exposure route and species on the acute lethal toxicity and tissue
concentrations of cyanide, in Developments in the Science and Practice of Toxicology, Hayes, A.W.,
Schnell, R.C., and Miya, T.S., Eds., Elsevier, Amsterdam, 1983, p. 583.
18. Tewe, O.O. and Pessu, E., Performance and nutrient utilization in growing pigs fed cassava peel rations

containing different cyanide levels, Nutr. Rep. Int., 26, 51, 1982.
19. Tewe, O.O., Effect of cassava-based diets varyingin cyanide content on the performance and physiopath-
ology of the African giant rat (Cricetomys gambianus Waterhouse), Anim. Feed Sci. Tech., 11, 1,
1984.
© 2006 by Taylor & Francis Group, LLC
International Agricultural Research, News Letter, 3, www.worldbank.org/html/cgiar/newsletter/Oct96/
6cgnews.html, 1996.
308 Cyanide in Water and Soil
20. MacMillan, V.H., Cerebral energy metabolism in cyanide encephalopathy, J. Cerebr. Blood F. Met.,9,
156, 1989.
21. McNamara, B.P., Estimates of the toxicity of hydrocyanic acid vapors in man, Report EB-TR-76023,
U.S. Department of the Army, Edgewood Arsenal, Aberdeen Proving Ground, MD, 1976.
22. Willhite, C.C. and Smith, R.P., The role of cyanide liberation in the acute toxicity of aliphatic nitriles,
Toxicol. Appl. Pharmacol., 59, 589, 1981.
23. Ma,J.andPristos, C.A., Tissue-specific bioenergetic effects and increasedenzymaticactivities following
acute sublethal peroral exposure to cyanide in the mallard duck, Toxicol. Appl. Pharm., 142, 297, 1997.
24. Wiemeyer, S.N., Hill, E.F., Carpenter, J.W., and Krynitsky, A.J., Acute oral toxicity of sodium cyanide
in birds, J. Wildlife Dis., 59, 589, 1986.
25. Henny, C.J., Hallock, R.J., and Hill, E.F., Cyanide and migratory birds at gold mines in Nevada, USA,
Ecotoxicology, 3, 45, 1994.
26. Spector, W.S., Acute toxicities of solids, liquids, and gasses to laboratory animals, in Handbook of
Toxicology, Vol. 1, WB Saunders Company, Philadelphia, PA, 1956, p. 408.
27. Gomez, G., Valdivieso, M., Santos, J., and Hoyos, C., Evaluation of cassava root meal prepared form
low- or high-cyanide containing cultivars in pig and broiler diets, Nutr. Rep. Int., 28, 693, 1983.
28. Allen, C.H., Mitigating impacts to wildlife at FMC Gold Company’s Paradise Peak mine, in Proceedings
of Nevada Wildlife/Mining Workshop, Reno, NV, March 27–29, 1990.
29. Clark, D.R. and Hothem, R.L., Mammal mortality at Arizona, California, and Nevada gold mines using
cyanide extraction, California Fish Game, 77, 61, 1991.
30. Tewe, O.O., Effect of dietary cyanide on the performance, metabolism and pathology of the African rat
(Cricetomys gambianus Waterhouse), Nutr. Rep. Intl, 26, 529, 1982.

31. Gensemer, R.W., Volosin, J., Clark, J.M., and Cardwell, R.D., Are ambient water quality criteria for
cyanide protective of aquatic-dependent wildlife?, in Proceedings of Fourth SETAC World Congress,
Society of Environmental Chemistry and Toxicology, Portland, OR, USA, 2004, p. 258.
32. USEPA, Ambient water quality criteria for cyanide, Report EPA 440/5-80-037, U.S. Environmental
Protection Agency, Office of Water, Washington DC, 1980.
33. Keinston, R.C., Cabellon, J.S., and Yarbrough, K.S., Pyridoxal 5

-phosphate as an antidote for cyanide,
spermine, gentamicin, and dophamine toxicity: an in vivo rat study, Toxicol. Appl. Pharm., 88, 433,
1987.
34. Chen, K.K. and Rose, C.L., Nitrite and thiosulfate therapy in cyanide poisoning, JAMA, 149, 113, 1952.
© 2006 by Taylor & Francis Group, LLC