# Update of Human Health Ambient Water Quality Criteria: Cyanide 57

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- 03 1 June 2015



# Update of Human Health Ambient Water Quality Criteria: Cyanide 57

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Office of Science and Technology Office of Water U.S. Environmental Protection Agency Washington, DC 20460Cyanide 57

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Table of Contents
1 Introduction: Background and Scope of Update

..................................................................... 2 2 Problem Formulation

............................................................................................................... 3 3 Criteria Formulas: Analysis Plan

.............................................................................................. 4 4 Exposure Factors

..................................................................................................................... 5 4.1 Body W eight

.................................................................................................................. 5 4.2 Drinking Water Intake

................................................................................................... 6 4.3 Fish Consumption Rate

................................................................................................ . 6 4.4 Bioaccumulation Factor

................................................................................................ 7 4.4.1 Approach

......................................................................................................... 7 4.4.2 Chemical

- specific BAFs

.................................................................................... 9 5 Hazard Identification and Dose Response

............................................................................... 9 5.1 Approach

....................................................................................................................... 9 5.2 Chemical

- spe cific Toxicity Value

................................................................................. 11 5.2.1 Reference Dose

.............................................................................................. 11 5.2.2 Cancer Slope Factor

....................................................................................... 12 6 Relative Source Contribution

................................................................................................ . 12 6.1 Approach

..................................................................................................................... 12 6.2 Chemical

- specific RSC

................................................................................................ . 13 7 Criteria Derivation: Analysis

.................................................................................................. 14 7.1 AWQC for Noncarcinogenic Toxicological Effects

...................................................... 15 7.2 AWQC for Carcinogenic Toxicological Effects

............................................................. 15 7.3 AWQC Summary

......................................................................................................... 16 8 Criteria Characterization

........................................................................................................ 17 9 Chemical Name and Synonyms

............................................................................................. 18 10 References

............................................................................................................................. 19

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1 Introduction: Background and Scope of Update EPA’s recommended ambient water quality criteria (AWQC) for human health are scientifically derived numeric values that EPA has determined will adequately protect human health from the adverse effects of pollutants in ambient water. Section 304(a)(1) of the Clean Water Act (CWA) requires EPA to develop and publish, and from time to time revise, recommended criteria for the protection of water quality that accurately reflect the latest scientific knowledge. Water quality criteria developed under section 304(a) are based solely on data and scientific judgments on the relationship between pollutant concentrations and environmental and human health effects. Section 304(a) criteria do not reflect cons ideration of economic impacts or the technological feasibility of meeting pollutant concentrations in ambient water. EPA’s recommended section 304(a) criteria provide technical information for states and authorized tribes a to consider and use in adopting w ater quality standards that ultimately provide the basis for assessing water body health and controlling discharges of pollutants into waters of the United States. Under the CWA and its implementing regulations, states and authorized tribes are required to adopt water quality criteria to protect the designated uses of waters (e.g., public water supply, aquatic life, recreational use, industrial use). EPA’s recommended water quality criteria do not substitute for the CWA or regulations, nor are they regulati ons themselves. Thus, EPA’s recommended criteria do not impose legally binding requirements. States and authorized tribes may adopt, where appropriate, other scientifically defensible water quality criteria that differ from these recommendations.
The water quality criteria that are the subject of this document are national AWQC recommendations for human health issued under CWA section 304(a). Unless expressly indicated otherwise, all references to “criteria,” “water quality criteria,” “ambient water quality criteria recommendations,” or similar variants thereof are references to national AWQC recommendations for human health. In this 2015 update, EPA has revised the human health criteria for cyanide to reflect the latest scientific information, including updated exposure fa ctors (body weight [BW], drinking water intake [DI] rate, and fish consumption rate [FCR]), bioaccumulation factors (BAFs), and human health toxicity value s ( reference dose [RfD] multiplied by relative source contribution [RSC] or 10 -6 d ivided by cancer slope factor [CSF]). Th e criteria continue to be based on EPA’s Methodology for Deriving Ambient Water Quality Criteria for the Protection of Human Health , which is referred to as the “2000 Methodology” in this document (USEPA 2000a) . EPA accepted written scientific views f rom the public on the draft updated human health criteria for this chemical (and 93 others) from May t hrough August 2014.

a Throughout this document, the term states means the 50 states, the District of Columbia, the Commonwealth of Puerto Rico, the Virgin Islands, Guam, American Samoa, and the Commonwealth of the Northern Mariana Islands. The term authorized tribe or tribe means an Indian tribe authorized for treatment in a manne r similar to a state under CWA s ection 518 for the purposes of s ection 303(c) water quality standards

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I t is important for s tates and authorized t ribes to consider any new or updated section 304(a) recommended criteria as part of their t riennial review process to ensure that state or tribal water quality standards reflect current science and protect applicable designated uses. These final 2015 updated section 304(a) human health criteria recommendations supersede EPA’s previous recommenda tions.
2 Problem Formulation Problem formulation provides a strategic framework for water quality criteria development by focusing on the most relevant endpoints and increasing the transparency of the effects assessment. The structure of this criteria docume nt is intended to be consistent with general concepts of effects assessments as described in EPA’s Framework for Human Health Risk Assessment to Inform Decision Making (USEPA 2014a)

. In developing AWQC, EPA currently follows the assessment method outlined in its 2000 Methodology (USEPA 2000a)

. The 2000 Methodology describes different approaches for addressing water and non

- water exposure pathways to derive human health AWQC depending on the toxicological endpoint of concern, the toxicological effect (non carcinogenic or carcinogenic ), and whether toxicity is considered a linear or threshold effect. Water sources of exposure include both co nsuming drinking water and eating fish or shellfish from inland and nearshore waters that have been exposed to pollutants in the water body

. For pollutants that exhibit a threshold of exposure before deleterious effects occur, as is the case for noncarcino gens and nonlinear carcinogens, EPA applies an RSC to account for other potential human exposures to the pollutant (USEPA 2000a)

. Other sources of exposure m ight include, but are not limited to, exposure to a particular pollutant from ocean fish or shellfish consumption (which is not includ ed in the FCR ), non

- fish food consumpt ion (e.g., consumption of fruits, vegetables, grains , meats, or poultry ), dermal exposure, and inhalation exposure. For substances for which the toxic ity endpoint is carcinogenicity based on a linear low

- dose extrapolation, only the exposures from drinking water and fish ingestion are reflected in human health AWQC; that is , non - water sources are not explicitly included and no RSC is applied (USEPA 2000a) . In these situations, AWQC are deri ved with respect to the incremental lifetime
cancer risk posed by the presence of a substance in water, rather than an individual’s total risk from all sources of exposure. The resulting criterion represent s the water concentration that is expected to incr ease an individual’s lifetime risk of ca ncer from exposure to the particular pollutant by no more than one chance in one million for the general population. EPA calculates AWQC at a 10 - 6 (one in one million) cancer risk level for the general population (USEPA 2000a)

. The 2000 Methodology re commends that states set human health criteria cancer risk levels for the target general population at either 10

- 5 or 10 - 6 and also notes that states and authorized t ribes can choose a more stringent risk level, such as 10

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. For substances that are carcin ogenic, EPA takes an integrated approach and considers both cancer and n oncancer effects when deriving AWQC (USEPA 2000a; USEPA 2000b)

. Where sufficient data are available, EPA derives AWQC using both c arcinogenic and noncarcinogenic toxicity endpoints and recommends the lower value fo r the AWQC. The AWQC might not utilize

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the value obtained from the cancer analysis if it is less protective than that derived from the noncancer endpoint

. 3 Criteria Formulas : Analysis Plan Human health AWQC for toxic pollutants are necessary to protect any designated uses related to ingestion of water and ingestion of aquatic organisms. These uses can include, but are not limited to, recreation in and on the water, consumption of fish or shellfish (including consumption associated with fishing or shellfish harvesting), and protecti on of drinking water supplies.
The derivation of human health AWQC requires information about both the toxicological endpoints of concern for water pollutants and the pathways of human exposure to those pollutants. EPA considers the following two primary pathways of huma n exposure to pollutants present in a particular water body when deriving human health 304(a) AWQC: (1) d irect ingestion of drinking water obtained from the water body and (2) c onsumption of fish or shellfish obtained from the water body. The equations for deriving human health AWQC for non carcinogenic effects and carcinogenic effects are presented as Eq s . 1 and 2. EPA d erives recommended human health AWQC based on the consumption of both water and aquatic organisms (Eq

. 1) and based on the consumption of aquatic organisms alone (Eq

. 2). The use of one criterion over the other depends on the designated use of a particular water body or water bodies (i.e., drinking water source and/or fishable waters). EPA recommends applying organism

- only AWQ C (Eq. 2) to a water bod y where the designated use includes supporting fishable uses under section 101(a) of the CWA but the water body is not a drinking water supply source (e.g., non

- potable estuarine waters that support fish or shellfish for human consu mption) (USEPA 2000a)

. EPA recommen ds inclu ding the drinking water exposure pathway for ambient surface waters where drinking water is a designated use for the following reasons: (1) drinking water is a designated use for surface waters under the CWA , and therefore criteria are needed to en sure that this designated use can be protected and maintained; (2) although they are rare, some public water supplies provide drinking water from surface water sources without treatment; (3) even among the majority of water supplies that do treat surface w aters, existing treatments m ight not be effective for reducing levels of particular contaminants; and (4) in consideration of the Agency’s goals of pollution prevention, ambient waters should not be contaminated to a level where the burden of achieving hea lth objectives is shifted away from those responsible for pollutant discharges and placed on downstream users that must bear the costs of upgraded or supplemental water treatment (USEPA 2000a)

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The equations for deriving the criteria values are as follows (USEPA 2000a) : For consumption of water and organisms: AWQC (μg/L) = toxicity value (mg/kg

- d) × BW (kg) × 1 , 000 ( μg/mg ) b (Eq. 1) DI (L/d) + ∑ (FCR i (kg/d) × BAF i (L/kg)) 4 i=2 For consumption of organisms only: AWQC (μg/L) = toxicity value (mg/kg

- d) × BW (kg) × 1 , 000 ( μg/mg ) c (Eq. 2) ∑ (FCR i (kg/d) × BAF i (L/kg))

4 i=2 Where: A WQC = ambient water quality criteria toxicity value = RfD x RSC ( mg/kg

- d) for non carcinogenic effects
or 10 -6 /CSF ( kg

- d/mg) for carcinogenic effects d RSC = relative source contribution (applicable to only noncarcinogenic and nonlinear low

- dose extrapolation for carcinogenic effects) BW = body weight DI = drinking water intake ∑ 4

i=2 = summation of values for aquatic trophic levels (TLs), where the letter i stand s for the TLs to be considered, starting with TL2 and proceeding to TL4 FCR i = fish consumption rate for aquatic TLs 2, 3, and 4 BAF i = bioaccumulation factor for aquatic TLs 2, 3, and 4 EPA rounds AWQC to the number of significant figures in the least pre cise parameter as described in the 2000 Methodology (USEPA 2000a , s ection 2.7.3).
4 Exposure Factors
4.1 Body Weight EPA updated the default BW assumption to 80 .0 kg based on National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2006 as r eported in Table 8.1 of EPA’s Exposure Factors Handbook (USEPA 2011a) . The updated BW represents the mean weight for adults ages 21 and older. EPA’s previously recommended BW assumption for adults was 70 kg, which was based on the mean BW of adults from the NHANES III database (1988

– 1994) and a 1989 study conducted by the National Cancer Institute (USEPA 2000a)

.

b 1,000 μg/mg is used to convert the units of mass from milligrams to micrograms.

c 1,000 μg/mg is used to convert the units of mass from milligrams to micrograms. d 10 -6 or 1 in 1,000,000 risk level for the general population.

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4.2 Drinking Water Intake
EPA updated the default DI to 2.4 L/d, rounded from 2.414 L/ d, based on NHANES data from 2003 to 2006 as reported in EPA’s Exposure Factors Handbook (USEPA 2011a , Table 3

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. This rate represents the per capita estimate of combined direct and indirect community water e ingestion at the 90 th percentile for adults ages 21 and older

. EPA selected the per capita rate for the updated DI because it represents the average daily dose estimates ; that is , it includes both people who drank water during the survey period and those who did not , which is appropriate for a national

- scale assessment such as CWA section 304(a) national human health criteria development (USEPA 2011a , secti on 3.2.1 ).
EPA’s updated DI of 2.4 L/ d is consistent with the 2000 Methodology . In that document, EPA recommended a default DI of 2 L/d , which represented the per capita community water ingestion rate at the 86 th percentile for adults surveyed in the U .S. Department of Agriculture’s 1994

– 1996 Continuing Survey of Food Intake by Individuals (CSFII) analysis (USEPA 2000a , section 4.3.2.1 ).
4.3 Fish Consumption Rate The updated FCR for the general adult population is 22.0 g/d, or 0.0220 kg/d (USEPA 2014b , Table 9a ). This FCR represents the 90 th percentile per capita consumption rate of fish from inland and nearshore waters for U.S. adults ages 21 years and older based on NHANES data from 2003

– 2010. The 95 percent confidence interval (CI) of the 90 th percentile per capita FCR is 19.1 g/d and 25.4 g/d. This updated FCR replaces EPA’s previously recommended default FCR of 17.5 g/d, which represented an estimate of the 90 th percentile per capita consumption rate of fish from inland and nearshore waters for U.S. adults ages 21 years and older. That de fault FCR was based on USDA’s CSFII 1994

– 1996 data (USEPA 2002a)

. As recommended in the 2000 Methodology, EPA updated the AWQC to reflect trophic level - (TL -) specific FCRs to better represent human dietary consumption of fish. An organism’s trophic position in the aquatic food web can have an important effect on the magnitude of bioaccumulation of certain chemicals. The TL

- specific FCRs are numbered 2, 3, and 4, and they account for different categories of fish and shellfish species based on their position in the aquatic food web: TL2 accounts for benthic filter feeders; TL3 accounts for forage fish; and TL4 accounts for predatory f ish (USEPA 2000a)

. EPA used the fol lowing TL

- specific FCRs to derive the updated AWQC: TL2 = 7.6 g/d (0.0076 kg/d ) (95 percent CI [6.4, 9.1] g/d ); TL3 = 8.6 g/d (0.0086 kg/d) (95 percent CI [7.2, 10.2] g/d ) ; and TL4 = 5 .1 g/d (0.005 1 kg/d) (95 percent CI [4.0, 6.4] g/d )

. Each TL

- specific FC R represent s the 90 th percentile per capita consumption rate of fish and shellfish from inland and nearshore waters from that particular TL for U.S. adult s ages 21 years and older (USEPA 2014b ,

e Community water includes direct and indirect use of tap water for household uses and excludes bottled water and other sources (USEPA 2011a, section 3.3.1.2 ). Direct ingestion is defined as direct consumption of water as a beverage, while indirect ingestion includes water added during food preparation (e.g., cooking, rehydration of beverages) but not water intrinsic to purchased foods (USEPA 2011a, section 3.1 ).

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Tables 16a, 17a, and 18a ) . The sum of these three TL

- specific FCRs is 21.3 g/d, which is within the 95 perce nt CI of the overall FCR of 22.0 g/d. EPA recommends using the TL

- specific FCRs when deriving AWQC; however, the overall FCR rate (22.0 g/d) may be used if a simplified approach is preferred.
4.4 Bioaccumulation Factor
4.4.1 Approach Several attributes of the bioacc umulation process are important to understand when deriving national BAFs for use in developing national recommended section 304(a) AWQC. First, the term bioaccumulation refers to the uptake and retention of a chemical by an aquatic organism from all surrounding media, such as water, food, and sediment. The term bioconcentration refers to the uptake and retention of a chemical by an aquatic organism from water only. For some chemicals (particularly those that are highly persistent and hydrophobic), the magn itude of bioaccumulation by aquatic organisms can be substantially greater than the magnitude of bioconcentration. Thus, an assessment of bioconcentration alone might underestimate the extent of accumulation in aquatic biota for those chemicals. Accordingl y, the EPA guidelines presented in the 2000 Methodology emphasize using, when possible, measured or estimated BAFs, which account for chemical accumulation in aquatic organisms from all potential exposure routes (USEPA 2000a)

. EPA estimated BAFs for this updated AWQC using EPA’s 2000 Method ology (USEPA 2000a) and its Technic al Support Document, Volume 2: Development of National Bioaccumulation Factors (Technical Support Document, Volume 2) (USEPA 2003a) . Specifically, these documents provide a framework for identifying alternative procedures to derive national TL

- specific BAFs for a chemical based on the chemical’s properties (e.g., ionization and hydrophobicity), metabolism, and biomagnification potenti al (USEPA 2000a; USEPA 2003a)

. EPA’s appro ach for developing national BAFs represents the long

- term average bioaccumulation potential of a pollutant in aquatic organisms that are commonly consumed by humans across the United States. National BAFs are not intended to reflect fluctuations in bioaccu mulation over short periods (e.g., a few days) because human health AWQC are generally designed to protect humans from long

- term (lifetime) exposures to waterborne chemicals (USEPA 2003a)

. EPA followed the approach described in Fi gure 3

- 1 of the Technical Support Document, Volume 2 (USEPA 2003a) . EPA used peer

- reviewed, publicly available information to classify each chemical using this framework to derive the most appropriate BAFs according to EPA’s 2000 Methodology (USEPA 2000a) . The fram ework provides six alternatives, or procedures, resulting in up to four possible methods for each chemical, based on the chemical’s properties. These four methods follow:

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• BAF Method. This method uses measured BAFs derived from data obtained from field stud ies. Field

- measured BAFs were normalized by adjusting for the water

- dissolved portions of the chemical and the lipid fraction of fish tissue for each species, as well as the fraction of the total concentration of chemical in water that is freely dissolved. EPA averaged multiple field BAFs using a geometric mean of the normalized BAFs by species and TL ; then EPA further averaged the BAFs across species to compute TL baseline BAFs. The national

- level BAF adjusts the TL baseline BAFs by national default values for lipid content, dissolved and particulate organic carbon content, and the n

- octanol

- water partition coefficient (K ow ). EPA chose the recommended 50 th percentile dissolved and particulate organic carbon content for the national

- level default values, as described in section 6.3 of the Technical Support Document, Volume 2 (USEPA 2003a)

. • BSAF Method. This method uses biota

- sediment accumulation factors (BSAFs) to estimate BAFs. EPA did not use measured BSAFs to calculate national BAFs because the two major compilations of these data

— EPA’s Biota

- Sediment Accumulation Factor Data Set, Version 1.0 (USEPA 2015a) , and the U.S. Army Corps of Engineers’ BSAF database (USACE 2015)

— have not been peer

- reviewed.

• BCF Method. This method uses BAFs estimated from laboratory

- measured bioconcentration factors (BCFs) with or without adjustment by a food chain multiplier. Similar to field BAFs, laboratory

- measured BCFs are normalized with the lipid fraction and the fraction of the total concentration of chemical in water that is freely dissolved, then multiplied by the food chain multiplier where applicable. Multiple values are averaged using a geometric mean across species and then across TL to compute baseline BAFs. The national

- level BAF adjusts the TL baseline BAFs by national default values for lipid content, dissolved and particulate organic carbon content, and the K ow . EPA chose the recommended 50 th percentile dissolved and particulate organic carbon content for the national

- level default values, as described in section 6.3 of the Technical Support Document, Volume 2 (USEPA 2003a)

. • K ow Method. This method predicts BAFs based on a chemical’s K ow , with or without adjustment using a food chain multiplier, as described in section 5.4 of the Technical Support Document, Volume 2 (USEPA 2003a)

. Following the decision framework presented in Figure 3

- 1 of the Technical Support Document, Volume 2 (USEPA 2003a) , EPA selected one of the six procedures to develop a national

- level BAF for this chemical. For a given procedure, EPA selected the method that provided BAF estimates for all three TL s (TL2

– TL4) in the following priority:
1. BAF estimates using the BAF method (i.e., based on field

- measured BAFs) if possible. 2. BAF estimates using the BCF method if (a) the BAF method did not produce estimates for all three TL s and (b) the BCF method produced nation al

- level BAF estimates for all three TL s. 3. BAF estimates using the K ow method if (a) Procedure 1 or 3 was applicable (see Figure 3- 1 of the Technical Support Document, Volume 2 [ USEPA 2003a ] ) and (b) the BAF and BCF methods did not produce BAF estimates for all three TL s.

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In cases where the procedure called for the BAF method but there were fewer than three TL estimates and the K ow method did not apply (i.e., Procedures 2, 4, 5, and 6), EPA used the BAF method estimate for the reported TL s by averaging the estimates using a geometric mean when there were two BAFs and us ing the single estimate when only one was available. EPA did not mix values from the BAF and BCF methods. If the BAF method did not have sufficient reliable data for any TL s, EPA used the BCF method estimates in the same manner. If none of the four methods provided sufficient data, or if none were appropriate for the procedure, EPA used the BCF from the previously recommended 2 002/2003 criteria (USEPA 2002b; USEPA 2003b)

. EPA primarily used field

- measured BAFs and laboratory

- measured BCFs available from peer

reviewed, publicly available databases (Arnot and Gobas 2006; E nvironment Canada 2006) to develop national BAFs. If field

- measured BAFs and laboratory

- measured BCFs were not available from those sources, EPA selected K ow values from peer

- reviewed sources (i.e., Agency for Toxic Substances and Disease Registry [ATSD R] preferentially, followed by U.S. Department of Health and Human Services ’ Hazardous Substances Data Bank ) for use in calculating national BAFs using the K ow method described in EPA’s Technical Support Document, Volume 2 (USEPA 200 3a) . For those chemicals for which the K ow method was not applicable based on the Technical Support Document, Volume 2 (USEPA 2003a) , EPA performed open literature searches of peer

- reviewed journal articles to find field

- measur ed BAFs or laboratory

- measured BCFs.
4.4.2 Chemical

- specific BAFs EPA selected a national BCF value of 1 L/kg for cyanide

. EPA followed the framework for selection of methods for deriving national BAF s in Fig ure 3

- 1 of the Technical Support Document, Volume 2 (USEPA 2003a) to select a procedure for estimating national BAFs for cyanide. Based on the characteristics this chemical, EPA selected Procedure 5 for deriving a national BAF value. Cyanide has the following characteristics:

• Inorg anic chemical

• Biomagnification unlikely (ATSDR 2006)
EPA was not able to locate peer

- reviewed, field

- measured BAFs or lab

- measured BCFs for all three TL s (2, 3, and 4) . Therefore, EPA is using the national BCF value of 1 L/kg from EPA’s National Recommended Water Quality Criteria for the Protection of Human Health for c yanide (USEPA 2003b)

. 5 Hazard Identification and Dose Response
5.1 Approach EPA considered all available toxicity values for both noncarcinogenic and carcinogenic toxicological effects to develop this updated AWQC for cyanide . As described in the 2000 Methodology (USEPA 2000a) , where data are available EPA derives AWQC for both

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noncarcinogenic and carcinogenic effe cts and recommends the more protective value for the AWQC. (S ee section 7, Criteria Derivation: Analysis .) For noncarcinogenic toxicological effects, EPA uses a chronic

- duration oral RfD to derive human health AWQC. An RfD is an estimate (with uncertainty spanning perhaps an order of magnitude) of a daily oral exposure of the human population to a substance that is likely to be without an appreciable risk of deleterious effects during a lifetime. An RfD is typically derived from a laboratory animal dosing s tudy in which a no

- observed

- adverse

- effect level (NOAEL), lowest

observed

- adverse

- effect level (LOAEL), or benchmark dose can be obtained. Uncertainty factors are applied to reflect the limitations of the data (USEPA 2000a)

. For carcinogenic toxicological effects, EPA uses an oral CSF to de rive human health AWQC . The oral CSF is an upper bound, approximating a 95 percent confidence limit, on the increased cancer risk from a lifetime oral exposure to a stressor. For this update, EPA conducted a systematic search of eight peer - reviewed, publicly available sources to obtain the toxicity value (RfD or CSF) for use in developing AWQC

. EPA’s primary source of toxicity values for developing human health AWQC is its Integrated Risk Information System (IRIS) program (USEPA 2015b)

. EPA also systematically searched for toxicological assessments from the following EPA program offices, other national and international programs, and state programs:

• EPA , Office of Pesticide Programs (USEPA 2015c)

• EPA, Office of Pollution Prevention and Toxics (USEPA 2015d)

• EPA, Office of Water (USEPA 2015e)

• EPA, Office of Solid Waste and Emergency Response (USEPA 2015f)

• U.S. Department of Health and Human Services , Agency for Toxic Substances and Disease Reg istry (ATSDR 2015)

• Health Canada (HC 2015)

• California Environmental Protection Agency, Office of Environmental Health Hazard Assessment (CalEPA 2014)
After identifying and documenting all available toxicity values, EPA followed a systematic process to select the toxicity value s used to derive the AWQC for noncarcinogenic and carcinogenic effects. EPA selected IRIS toxicity value s to derive the updated AWQC if any of the following conditions were met:
1. EPA’s IRIS toxicological assessment was the only available sourc e of a toxicity value. 2. EPA’s IRIS toxicological assessment was the most current source of a toxicity value. 3. EPA’s IRIS program was reassessing the chemical in question and had published the draft Toxicological Review for public review and comment, discussion at a public meeting, and subsequent expert peer review

. f

f Equivalent to Step 4 in the July 2013 EPA Process for Developing IRIS Health Assessments. Available online at http://www.epa.gov/iris/ process.htm

.

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4. The toxicity value from a more current toxicological assessment from a source other than EPA IRIS was based on the same principal study and was numerically the same as
an older EPA IRIS toxicity v alue

. 5. A more current toxicological assessment from a source other than EPA IRIS was available, but it did not include the relevant toxicity value (chronic

- duration oral RfD or CSF)

. 6. A more current toxicological assessment from a source other than EPA IRIS was available, but it did not introduce new science (e.g., the toxicity value was not based on a newer principal study) or use a more current modeling approach compared to an older EPA IRIS toxicological assessment.

EPA selected the toxicity value from a p eer - reviewed, publicly available source other than EPA IRIS to derive the upd a ted AWQC if any of the following conditions were met:
1. The chemical is currently used as a pesticide , and EPA Office of Pesticide Programs had a toxicity value that was used in pesticide registration decision

- making

. 2. A toxicological assessment from a source other than EPA IRIS was the only available source of a toxicity value. 3. A more current toxicological assessment from a source other than EPA IRIS introduced
n ew science (e.g., the toxicity value was based on a newer principal study) or used a more current modeling approach compared to an older EPA IRIS toxicological assessment.

5.2 Chemical

- specific Toxicity Value
5.2.1 Reference Dose EPA selected an RfD of 6 × 10 –4 mg/k g- d (0.0006 mg/kg

- d) for free cyanide based on a 2010 EPA IRIS assessment for hydrogen cyanide and cyanide salts (USEPA 2010a)

. EPA IRIS states that the “use of the RfD for free cyanide to calculate RfDs of other cyanide compounds may be merited , but the ability of the individual cyanogenic species to dissociate and release free cyanide in aqueous solution (and at physiological pHs) should be taken into consideration. If dissociation of the compound is expected, then liberated cations should be c onsidered for potential toxicity independent of CN
– . Also, some metallocyanides, such as copper cyanide, have chemical

specific data and are not included in this (IRIS) analysis” (USEPA 2010a)

. EPA’s IRIS program identified a study by the Natio nal Toxicology Program (NTP 1993) as the critical study and decreased cauda epididymis weight as the critical effect in male rats exposed to cyanide in drinking water (USEPA 2010a)

. The lower

- bound confidence limit on the benchmark dose ( BMDL 1SD ) is 1.9 mg/kg -d. In deriving the RfD, EPA’s IRIS program applied a composite uncertainty factor of 3000 to account for interspecies extrapolation (10), intraspecies variation (10), subchr onic

- to

- chronic exposure extrapolation (10), and database deficiencies (3) (USEPA 2010a)

.

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EPA identified two other RfD sources through the systematic search described in section 5 : a 2006 ATSDR assessment (ATSDR 2006) and a 1997 California EPA assessment (CalEPA 1997)

. Based on the selection process described in section 5, the IRIS RfD is preferred for use in AWQC development at this time. T he 2010 EPA IRIS assessment is the most current RfD source.
5.2.2 Cancer Slope Factor Under the 2005 E PA Guidelines for Carcinogen Risk Assessment (USEPA 2005) , t here is “inadequate information to assess the carcinogenic potential” of cyanide (USEPA 2010b)

. EPA identified no CSF source through the systematic search described in section 5.
6 Relative Source Contribution
6.1 Approach Th e RSC component of the AWQC calculation allows a percentage of the RfD’s exposure to be attributed to the consumption of ambient water and fish and shellfish from inland and nearshore waters when there are other potential exposure sources. The RSC describes the portion of the RfD available for AWQC

- related sources (USEPA 2000a) ; the remainder of the RfD is allocated to other sources of the pollutant. The rationale for this approach is that for pollutants exhibiting threshold effects, the objective of the AWQC is to ensure that an individual’s total exposure from all sources does not exceed that threshold level. Exposures outside the RSC include, but are not limited to, exposure to a particular pollutant from ocean fish and shellfish consumption (which is not included in the FCR ), non

- fish food consumption (e.g., fruits, vegetables, grains, meats, poultry), dermal exposure, and respiratory exposure.
EPA derived a n RSC for each chemical included in this 2015 update by using the Exposure Decision Tree approach described in the 2000 Methodology (USEPA 2000a)

. To u s e th at approach, EPA compiled information for each chemical on its uses, chemical and physical properties, occurrences in other potential sources (e.g., air, food), and releases to the environment, as well as regulatory restrictions on other sources that are spe cific to the chemical (e.g., air quality standards, food tolerance levels) . The ATSDR “Toxicological Profiles” (ATSDR 201 5) were the primary sources for this information. EPA used t he Hazardous Substance Data Bank (HSDB) (USDHHS 2015) from the National Library of Medicine’s Toxicology Data Network (TOXNET) as the primary source for chemicals without ATSDR Toxicological Profiles. Both sources are peer - reviewed compilations of chemical information.
EPA used a dditional references , including the following, to obtain specific types of information and to supplement the information from ATSDR and the HSDB :

• EPA ’s Six

- Year Review s (drinking water data) (USEPA 2009a; USEPA 2009b)

. • FDA Total Di et Study (USFDA 2015)

. • FDA Everything Added t o Food in the United States (USFDA 2013)

. • EPA National Lake Fish Tissue Study (USEPA 2009c)

. • EPA Toxic Release Inventory (USEPA 2015g)

.

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• International Bottled Water Association Standards of Quality (IBWA 2012)

. • NOAA Mussel Watch (NOAA 2014)

. • A dditional sources as needed.

T o determine the RSC to be used in the AWQC calculation , EPA then used the information compiled for each chemical to address the questio ns posed in the Exposure Decision Tree

. Some of the important items evaluated in the Exposure Decision Tree follow:

• T he adequacy of the data available for each relevant exposure source and pathway

. • T he availability of sufficient information to characterize the likelihood of exposure to relevant sources

. • W hether there are significant known or potential uses/sources other than the source of concern (i.e., ambient water and fish/seafood from those waters)

. • W hether information o n each source is available to make a characterization of exposure
. In cases where there is a lack of environmental or exposure data, or both, the Exposure Decision Tree approach results in a recommended RSC of 20 percent. This 20 percent value for the RSC may be replaced where sufficient data are available to develop a scientifically defensible alternative value. When appropriate, if scientific data demonstrating that sources and routes of exposure other than water and fish from inland and nearshore waters are not anticipated for the pollutant in question, the RSC may be raised to 80 percent based on the available data (USEPA 2000a)

. 6.2 Chemical

- specific RSC Cyanide is used in some pesticide formulations and as an adjuvant or intensifier for defoliation and weed control (ATSDR 2006)

. Cyanide itself is not registered as a pesticide (USE PA 2015c)

. The physical properties and uses of this chemical indicate that the general population might be exposed to it primarily through ingestion of food and water and , to a lesser degree, air (ATSDR 2006)

. The vapor pressure of cyanide (630 mm Hg at 20 °C) indicates that volatilization is an important fate process for this chemical (ATSDR 2006) . Recent data from EPA’s Toxic Release Inventory indicate that almost 135,000 pounds of hydrogen cyanide were released to the air in 2013 (USEPA 2015g) . Some cyanide compounds are listed as hazardous air pollutants (USEPA 2013)

. Cyanide has also been detected in cigarette smoke, automobile exhaust, and house and building fire sm oke (ATSDR 2006) . Therefore, based on the chemical’s physical properties and prevalence, air is a potentially significant source of exposure to it

.

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Cyanide is regulated under the Safe Drinking Water Act , and EPA’s drinking water standard (maximum contaminant level) is 200 μg/L (as free cyanide) (USEPA 2014c) . Cyanide has been detected in treated drinking water (ATSDR 2006) , and it was detected in EPA ’ s Six

- Year Reviews (USEPA 2009a; USEPA 2009b) . The Standard of Quality for bottled water for cyanide is 100 μg/L (IBWA 2012)

. Therefore, finished drinking water is a potentially significant source of exposure to cyanide. Cyanide has been detected in food (ATSDR 2006) , and ferrocyanide salt is listed in the Everything Added to Food in the United States database (USFDA 2013) . Thus, ingestion of food is a potentially significant source of exposure to this chemical. The average log K ow for hydrogen cyanide is 0.87 (ATSDR 2006) . The BCF estimate for cyanide is 1 L/kg, which indicates cyanide has a low potential for bioaccumulation (USEPA 2011b)

. Recent e xposure information regarding concentrations of cyanide in fish and shellfish could not be identified . This chemical was not included in NOAA’s Mussel Watch Survey (NOAA 2014) , and it was not on the list of analytes in EPA’s National Lake Fish Tissue Study (USEPA 2009c)

. Thus, based on its low potential for bioaccumulation , exposure to this chemical from ingestion of fish and shellfish is not considered likely.
I n summary, based on the physical properties and available exposure information for cyanide, air, drinking water, and non

- fish food are potentially significant sources. Following the Exposure Decision Tree in EPA’s 2000 Methodology (USEPA 2000a) , significant potential sources other than fis h and shellfish from inland and nearshore waters and water ingestion exist (Box 8A in the Decision Tree ); however, information is not available to accurately characterize exposure from th o se different sources (Box 8B in the Decision Tree)

. Therefore, EPA r ecommends an RSC of 20 percent (0.20) for cyanide

. 7 Criteria Derivation : Analysis Table 1 summarizes the model inputs used to derive the 2015 updated human health AWQC that are protective of exposure to cyanide from consuming drinking water and eating fish and shellfish (organisms) from inland and nearshore waters

. The c riteria calculations are presented below. These updated criteria recommendations are based on the 2000 Methodology (USEPA 2000a) and the updated exposure assumptions described above . ( See section 4, Exposure Factors ; section 5, Hazard Identification and Dose Response; and section 6, Relative Source Contribution.)

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Table 1. Summary of I nput P arameters for 2015 H uman H ealth AWQC for C yanide Input Parameter Value RfD 0.0006 mg/kg

- d CSF No data RSC 0.20 BW 80.0 kg DI 2.4 L/d FCR 0.0 22 kg/d BCF 1 L/kg

7.1 AWQC for N oncarcinogenic Toxicological E ffects For consumption of water and organisms: AWQC (μg/L) = toxicity value (RfD [mg/kg

- d] × RSC) × B W (kg) × 1 , 000 ( μg/mg) DI (L/d) + (FCR (kg/d) × B CF (L/kg))

= 0.0006 mg/kg

- d × 0.20 × 80.0 kg × 1 , 000 μg/mg

2.4 L/d + ( 0.022 kg/d × 1 L/kg)

= 3.96 μg/L

= 4 μg/L (rounded) For consumption of organisms only: AWQC (μg/L) = toxicity value (RfD [mg/kg

- d] × RSC) × B W (kg) × 1 , 000 ( μg/mg) (FCR (kg/d) × B CF (L/kg))

= 0.0006 mg/kg

- d × 0.20 × 80.0 kg × 1 , 000 μg/mg

( 0.022 kg/d × 1 L/kg)

= 4 36 μg/L

= 400 μg/L (rounded)
7.2 AWQC for C arcinogenic Toxicological E ffects
EPA identif ied no CSF sources through the systematic search described above. (See section 5, Hazard Identification and Dose R esponse .) Therefore, EPA was unable to derive AWQC for carcinogenic toxicological effects.

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7.3 AWQC Summary EPA derive d the AWQC for cyanide using a noncarcinogenic toxicity endpoint. The updated human health AWQC for cyanide are 4 μg/L for consumption of water and organisms and 4 00 μg/L for consumption of organisms only g (Table 2). These updated criteria replace EPA’s previously published values (USEPA 2003b)

. Consistent with EPA’s previously published criteria for cyanide (USEPA 2003b) , these updated AWQC are expressed as total cyanide, even though the IRIS RfD used to derive the criterion is base d on free cyanide. The multiple forms of cyanide that are present in ambient water have significant differences in toxicity due to their differing abilities to liberate the CN

- moiety. Some complex cyanides require even more extreme condition s than refluxin g with su lfuric acid to liberate the CN

- moiety. Thus, these complex cyanides are expected to have little or no bioavailability to humans. If a substantial fraction of the cyanide present in a water body is present in a complexed form (e.g., Fe4[Fe(CN)6]3), these r ecommended criter ia may be over ly conservative (USEPA 2003b)

.
Table 2. Summary of EPA’s Previously Recommended (2003 ) and U pdated ( 2015 ) Human H ealth AWQC for C yanide 2003 Human Health AWQC 2015 Human Health AWQC Water and Organism 140 μg/L 4 μg/L Organism Only 140 μg/L 4 00 μg/L * *See footnote g. These AWQC are intended to be protective of the general adult population from noncarcinogenic effects due to chronic (up to a lifetime) e xposure to cyanide from ingesting water and/or consuming fish and shellfish from inland and nearshore waters.

g If a water body is not designated as a drinking water supply source, a state can adopt AWQC for consumption of organisms only instead of AWQC for consumption of water and organisms. EPA recommends, however, that the state evaluate whether or ganism

- only AWQC for non

- bioaccumulative chemicals pose a risk to swimmers in those water bodies. Because cyanide has no bioaccumulation potential (BCF = 1 L/kg), EPA performed a screening analysis to determine whether the updated AWQC for organisms only i s protective of incidental water ingesti on from recreational uses (see s ection 4.1.1.3 in USEPA 2000a) . EPA assumed an incidental water ingestion rate of 0.090 L/swimming event, which represents the upper (97 th ) percentile for children (Table 3

- 5 in USEPA 2011a) and a body weight of 31.8 kg, which represents the mean body weight of children ag es 6 to <11 years (Table 8

- 1 in USEPA 2011a) . No acute oral RfD was identified so EPA relie d on an intermediate duration (15

– 364 days) MRL for cyanide of 0.05 mg CN – /kg

- d (ATSDR 2006). The resulting incidental water ingestion value (for screening purposes only) is 17,667 μg/L [(0.05 mg/kg -d × 31.8 kg × 1,000 μg/mg) / 0.090 L/d]. Therefore, the updated AWQC for consumption of organisms only of 400 μg/L for cyanide is protective of incidental water inges tion from recreational uses. Where a water body is designated as a drinking water supply source EPA recommends the AWQC for consumption of water and organisms for cyanide ( 4 μg/L) (USEPA 2000a)

.

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8 Criteria Characterization The updated 2015 human health AWQC for cyanide take into account current data on health effects and exposure input parameters, consistent with the 2000 Methodology (USEPA 2000a)

. The following paragraphs describe the individual influence of each of the revi sed inputs and exposure assumptions on the overall change in value. Body Weight EPA’s updated AWQC assume a higher BW compared to the previously recommended 2002 criteria, reflecting a recent rise in average adult BW among the U.S. population. The updated BW assumption of 80.0 kg, based on recent survey data from the 1999−2006 NHANES data, is 10 kg greater than the previous assumption of 70 kg. Assuming all other input parameters remain constant, a higher average BW in the AWQC calculations (Eq s . 1 and 2 ab ove) results in higher AWQC. That is, as BW increases, the level of a contaminant in water at or below which negative health effects are not anticipated from a lifetime of exposure also increases. Drinking Water Intake The updated DI assumption is 2.4 L/d , which is higher than the previo usly recommended rate of 2 L/d . Assuming all other input parameters remain constant, a higher DI assumption in the AWQC calculations (Eq s . 1 and 2 above) results in lower AWQC. That is, as DI increases, and thus overall exposure increases, the level of a contaminant in water at or below which negative health effects are not anticipated from a lifetime of exposure decreases. Fish Consumption Rate The updated FCR for fish and shellfish from inla nd and nearshore waters is 22.0 g/d; the TL

- specific FCRs are 7.6 g/d, 8.6 g/d, and 5.1 g/d for TLs 2, 3, and 4, respectively. The previously recommended FCR was 17.5 g/d. Assuming all other input parameters remain constant, a higher FCR assumption in the AWQC calculations (Eqs. 1 and 2 above) results in lower AWQC. That is, as fish consumption increases, and thus overall exposure increases, the level of a contaminant in water at or below which negative health effects are not anticipated from a lifetime of exposure decreases.
Bioaccumulation Factor The updated AWQC rely on EPA’s 2000 Methodology (USEPA 2000a) and its Technical Support Document, Volume 2 (USEPA 2003a) to derive national TL

- specific BAFs. In cases where data were not available to calculate one or more TL

- specific BAFs, EPA relied on the BCF from the previously recommended 2003 criteria (USEPA 2003b) . The previously recommended BCF of 1 L/kg was used for cyanide. As an additional line of evidence, EPA used model

- estimated BAFs from the Estimation Progr am Interface (EPI) Suite (USEPA 2012) to support field

- measured or predicted BAFs developed using the four methods described above. The BCFBAF program within EPI Suite estimates fish BAF s by using K ow and biotransformation data from a model designed by Arnot and Gobas ( 2003) . The

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model includes mechanistic processes for bioaccumulation , such as chemical uptake from the water at the gill surface and from the diet, chemical elimination at the gill surface, fecal egestion, growth dilution , and metabo lic biotransformation. Other processes included in the calculations are bioavailability in the water column (only the freely dissolved fraction can bioconcentrate) and absorption efficiencies at the gill and in the gastrointestinal tract. The model require s the K ow of the chemical and the normalized whole

- body metabolic biotransformation rate constant as input parameters to predict BAF values. The EPI Suite model estimates are as follows :
TL 2 = 0.9634 L/kg TL 3 = 0.9561 L/kg TL 4 = 0.9202 L/kg

Reference Dose EPA selected an RfD of 0.0006 mg/kg

- d for free cyanide based on a 2010 EPA IRIS assessment for hydrogen cyanide and cyanide salts (USEPA 2010a) . This RfD replaces the previous value of 0.02 mg/kg

- d (USEPA 2003b)

. EPA used the RfD of 0.0006 mg/kg

- d to derive AWQC for noncarcinogenic effects. Assuming a ll other input parameters remain constant, a decreas e in the RfD in the AWQC calculations (Eqs

. 1 and 2) results in lower AWQC. Cancer Slope Factor EPA did not select a CSF for cyanide and therefore did not derive AWQC for carcinogenic effects. EPA did not derive AWQC for carcinogenic effects of cyanide in its previous criteria update (USEPA 2003b)

. Relative Source Contribution An RSC of 20 percent is included in the AWQC calculation. This is the same RSC used in the previous AWQC (USEPA 2003b)

. 9 Chemical Name and Synonyms

• Cyanide (CAS Number 57

- 12

- 5)

• Prussic acid

• Hydrocyanic acid

• Cyclone B

• Cyanogran

• Cymag

• Cyanobrik

• White cyanide

• Calcyanide

• Calcyan, cyanogas

• Black cyanide

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- 5

• Potassium dicyanoargentate

• Dicyanogen

• Ethanedinitrile

• Oxalonitrile

10 References Arnot, J.A., and A.P.C. Gobas. 2003. A Generic QSAR for Assessing the Bioaccumulation Potential of Organic Chemicals in Aquatic Food Webs. QSAR & Combinatorial Science 22:337

– 345. Arnot, J.A., and A.P.C. Gobas. 2006. A review of bioconcentration factor (BC F) and bioaccumulation factor (BAF) assessments for organic chemicals in aquatic organisms. Environmental Reviews 14(4):257

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ATSDR. 2006. Toxicological Profile for Cyanide . U.S. Department of Health and Human Services, U.S. Public Health Service, Agenc y for Toxic Substances and Disease Registry, Atlanta, GA. Accessed February 2015. http://www.atsdr.cdc.gov/toxprofiles/tp8.pdf

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. CalEPA. 1997. Public Health Goal for Cyanide in Drinking Water . California Environmental Protection Agency, Office of Environmental Health Hazard Assessment. Accessed March 2015. http://oehha.ca.gov/water/phg /pdf/cyan_c.pdf

. CalEPA. 2014. All Public Health Goals . California Environmental Protection Agency, Office of Environmental Health Hazard Assessment. Accessed February 2015. http://www.oehha.ca.gov/water/phg/allphgs.html

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NOAA. 2014. National Centers for Ocean and Coastal Science, National Status and Trends Data Portal (NCCOS NS&T Data Portal) . U.S. Department of Commerce, National Oceanic and Atmospheric Administration, National Centers for Ocean and Coastal Science, Silver Spring, MD. Accessed March 2015. http://egisws02.nos.noaa.gov/nsandt/index.html#

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.

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