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

Toxicity of Cyanide to Aquatic-Dependent Wildlife 287Biogenic sources of cyanide consist of various species of bacteria, algae, fungi, and higher plants in many food plants and forage cr

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

aquatic toxicity data that serve as the basis of the current national criteria [3; see alsoChapter 14]

286 Cyanide in Water and Soil

Here, we review the toxicity of cyanide compounds to aquatic-dependent wildlife exposed viadrinking water and food Our focus was to evaluate the bioavailability1of cyanide from differentexposure pathways and the degree to which toxicity changes when different cyanide compoundspass from the intestinal tract into the bloodstream More specifically, the purpose of this review is toevaluate 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 compoundsdiffer 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, andaquatic-dependent wildlife specifically?

Because toxicologic data for aquatic-dependent wildlife species are extremely limited, data forbirds and mammals commonly tested in the laboratory also were used Testing of surrogate animalspecies 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 includemining operations, manufacture of synthetic fabrics and plastics, pesticides, and production interme-diates in agricultural chemical production [6,7] Formation of cyanide compounds during treatmentonment include free cyanide, simple cyanides, metallocyanide complexes, thiocyanate, syntheticFree 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 orpotassium 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 centrations of which depend on pH and the metal’s affinity for the CN−ion (e.g., CdCN−, Cu(CN)−

con-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 thehigh affinity of CN− for Fe2 + and Fe3 +(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.

a result of certain chemical reactions (Chapter 4) In addition, they are formed naturally by certainplants (Chapter 3); for example, cyanogenic glycosides are produced in cassava and thiocyanate

of municipal wastewater can also occur [2; andChapter 25] Chemical forms of cyanide in the

envir-nitriles, and organic cyanides (Chapter 2)

and HCN [9; andChapter 5]

cyanide analytical method [2; and Chapters 5 and7]

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 itsimportance 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 mayingest 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 organiccyanide compound Hydrocyanic acid is readily absorbed by the guts of birds and mammals [10].Secondary poisoning3of terrestrial vertebrates from feeding on cyanide-poisoned invertebrates andfish 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 areusually 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] Hypoxiaconcomitantly causes a shift from aerobic to anaerobic metabolism, resulting in lactate acidosisthat lowers blood pH, and depresses the central nervous system, leading to respiratory arrest anddeath [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 severaldays [6] More minor detoxification pathways include exhalation of HCN and conjugation withcystene or hydroxocobalamin (vitamin B12) [6] Cyanide is readily absorbed into the bloodstreamand 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 Internetsearch 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 searchengines were used to scan the Internet for relevant articles using the keywords and phrases Thesesearches 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 studiesaccording to the criteria described in the following section No data for marine aquatic-dependentwildlife were found

3 Secondary poisoning represents toxicity to organisms that consume a cyanide-containing plant or animal.producing and excreting cyanide compounds (Chapter 3) Elevated concentrations of cyanide occur

288 Cyanide in Water and Soil

Reported data were screened according to the following criteria In some instances, these teria could not be applied, and in some instances where data were accepted, qualifications wereidentified

cri-• 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 observableadverse effect level (NOAEL) calculated using an acceptable statistical method for eachendpoint measured

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 betweenstudies 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 mgtested 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

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-oldchicks and lasted for nine weeks, during which time the concentration of cyanide in the food remainedunchanged, 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 benchmarksfor wildlife They proposed using the animal’s average body weight for the test period to calculateaverage 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] notethat this method over- and under-estimates food consumption (and hence dose) for younger and olderchicks, respectively, but is an acceptable estimate of the average dose

Toxicity of Cyanide to Aquatic-Dependent Wildlife 289

CN molecular weight Percent CN

15.4.2.2 Normalization of Toxic Dose to Cyanide Ion

After normalizing dosages based on total chemical concentrations, the data were normalized for CNdose (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 hinderingcomparison The methodology used by the European Commission [15] was adopted; it estimatesNOAEL 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 assessmentfactors are not well researched and are thus uncertain, especially for fast-acting gases like the freeand 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 pathwaysare shown inFigure 15.1 Raw data are provided inTables 15.2to15.4 Data for birds are shownwith the mammalian data inFigure 15.2, and raw data are listed inTables 15.5to15.7

290 Cyanide in Water and Soil

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 acumulative distribution function of the ranked NOAELs Data points corresponding to specific cyanide exposurepathways are denoted by (

Normalized cyanide NOAELs ranged from 0.005 to 80 mg CN/kg BW The lowest estimatedno-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/kgrepresenting 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 ofNOAELs 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 thanthose 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 muchgreater 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 theranges 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 exposureroute on the relative toxicity of cyanide to mammals and birds, and then in terms of differencesbetween mammals and birds for each exposure route

Two studies examined effects of drinking water exposure to two different wildlife species from threesimple cyanide compounds [16,17] Ballantyne’s [17] study with rabbits calculated very similar

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 15.7andFigure 15.2)

ranged from 5.9 to 79.6 mg CN/kg BW (Table 15.3and Figure 15.2), and included the single birdfood 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 (Table 15.2), and those for birds rangedfrom 0.01 to 0.8 mg CN/kg BW (Table 15.5)

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

7 to 15 kg

7 to 15 kg

© 2006 by Taylor & Francis Group, LLC

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

food

measured in cassava tuber

16.1 kg

CN of cassava

gain

Unbounded NOAEL

unknown

consumption, blood chemistry, behavior, or organ histology

food

measured in cassava tuber

© 2006 by Taylor & Francis Group, LLC

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

© 2006 by Taylor & Francis Group, LLC

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

in detail

© 2006 by Taylor & Francis Group, LLC

female not significantly different Study design not described in detail

unknown

described in detail

(Sprague–Dawley)

Unknown/ 250

to 260 g

unknown

described in detail

unknown

described in detail

unknown

described in detail

unknown

described in detail

unknown

described in detail

30 g

Acetone cyanohydrin

© 2006 by Taylor & Francis Group, LLC

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

© 2006 by Taylor & Francis Group, LLC