Office of Water Office Science and Technology EPA 820-D- 14 -0 53 May 2014



# Draft Update of Human Health Ambient Water Quality Criteria:

Isophorone
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# Update of Human Health Ambient Water Quality Criteria:

Isophorone
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Draft

Office of Science and Technology
Office of Water U.S. Environmental Protection Agency Washington, DC 20460Isophorone 78

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Table of Contents

Introduction: Plan and Scope of Update

Problem Formulation Criteria Formulas- Analysis Plan
Exposure Factors Body Weight Drinking Water Intake Fish Consumption Rate

Bioaccumulation Factor Hazard Identification and Dose Response: Cancer Slope Factor Criteria Derivation- Analysis

Criteria Characterization Chemical Name / Synonyms

References

Introduction: Plan and Scope of Update

Human health ambient water quality criteria (AWQC) are numeric values for pollutant concentrations in ambient waters that the U.S. Environmental Protection Agency (EPA)

consider s to be protective of human health. EPA periodically revises water quality criteria to ensure that they reflect the latest scientific knowledge. The current revisions of the criteria for isophorone, contained in this document, incorporate updated information regarding body weight, drinking water intake, fish consumption rate, and bioaccumulation. Updated body weight and drinking water intake data a ι͋ Ί͇͋ΣχΊ͕Ί͇͋ ΊΣ E ́!͛ν ·EϳζΪνϢι͋ F̯̽χΪιν H̯Σ͇̼ΪΪΙ ́ 2011 E͇ΊχΊΪΣ͛ (Ε΋E ́!΂ 2011). The bioaccumulation ͕̯̽χΪι ͇̯χ̯ Ίν Ϣζ͇̯χ͇͋ ϢνΊΣͽ E ́!͛ s Estimation Program Interface (EPI) Suite modeling program (USEPA, 2012a). The overall fish consumption rate and trophic level breakdowns are updated using E ́!͛ν ·EνχΊ΢̯χ͇͋ FΊν· ΪΣνϢ΢ζχΊΪΣ ·̯χ͋ν for the U.S. Population and Selected Subpopulations (NHANES 2003- 2010)͛ (Ε΋E ́!΂ 2014)

. Unless otherwise specified, all sources of information used in this update are from peer

reviewed sources.

Note that the term "water quality criteria" can carry one of two possible meanings, depending on the section of the Clean Water Act (CWA) associated with the particular criteria ̯χ ΊννϢ͋ ̈́ ͞Ρ̯χ͋ι θϢ̯ΜΊχΘ ̽ιΊχ͋ιΊ̯͟ ΢̯Θ ι͕͋͋ι χΪ Σ̯χΊΪΣ̯Μ Ϯ̯χ͋ι θϢ̯ΜΊχΘ ̽ιΊχ͋ιΊ̯ ι͋̽Ϊ΢΢͋Σ͇̯χΊΪΣν

issued under CWA § 304 ̈́ ͞Ρ̯χ͋ι θϢ̯ΜΊχΘ ̽ιΊχ͋ιΊ̯͟ ΢̯Θ ̯ΜνΪ ι͕͋͋ι χΪ Ϯ̯χ͋ι θϢ̯ΜΊχΘ ̽ιΊχ͋ιΊ̯ components of water quality standards adopted by states, territories, or authorized tribes
under CWA § 303.

National ambient water quality criteria recommendations for human health are issued by the EPA under CWA § 304. They are based on the latest scientific information on the relationship between the effects of a constituent concentration and human health. Protective assumptions are made regarding the potential human exposure intakes. These criteria do not reflect consideration of non-human health endpoints or economic impacts. Nor do they reflect

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the technological feasibility of meeting the chemical concentrations in ambient water. National ambient water quality criteria recommendations for human health are not automatically incorporated into water quality standards adopted by states, territories, or authorized tribes. Rather, they provide scientific information to states, territories and authorized tribes to assist them in adopting ambient water quality criteria for human health in water quality standards that meet CWA requirements. National ambient water quality criteria recommendations for human health are not regulations themselves and they do not impose legally binding requirements on EPA, states, territories, authorized tribes, or the public. States, territories, and authorized tribes have the discretion to adopt, where appropriate, other scientifically ͇͕͋͋ΣνΊ̼Μ͋ Ϯ̯χ͋ι θϢ̯ΜΊχΘ ̽ιΊχ͋ιΊ̯ χ·̯χ ͇Ί͕͕͋ι ͕ιΪ΢ E ́!͛ν Σ̯χΊΪΣ̯Μ ̯΢̼Ί͋Σχ ι͋̽Ϊ΢΢͋Σ͇͇͋ ̽ιΊχ͋ιΊ̯

for human health.

Ambient water quality criteria components of water quality standards are generally adopted by the states, territories, and authorized tribes themselves, under § 303(c)(2). (In certain circumstances EPA also may promulgate this type of criterion itself, pursuant to §303(c)(4)). State ambient water quality criteria for human health represent a quality of water that sufficiently protects human health to support a designated use of the state, territory, or authorized tribe. Such criteria may be expressed in terms of constituent concentrations, levels, or narrative statements. Once ambient water quality criteria for human health are adopted by a state, territory, or authorized tribe into their water quality standards, they provide a basis for controlling discharges or releases of pollutants, for developing permit limits, assessing waters, and developing total maximum daily loads (TMDLs) for waters that do not meet the water quality standard. Ambient water quality criteria for human health have a regulatory impact once they have been adopted into water quality standards by the state, territory, or authorized tribe under § 303(c)(2) (or alternatively issued by EPA pursuant to § 303(c)(4)).

The water quality criteria at issue in this document are national ambient water quality criteria recommendations for human health issued under CWA § 304. Unless expressly ΊΣ͇Ί̯̽χ͇͋ Ϊχ·͋ιϮΊν͋΂ ̯ΜΜ ι͕͋͋ι͋Σ̽͋ν χΪ ̽͞ιΊχ͋ιΊ̯΂͟ ͞Ϯ̯χ͋ι θϢ̯ΜΊχΘ ̽ιΊχ͋ιΊ̯΂͟ ̯͞΢̼Ί͋Σχ Ϯ̯χ͋ι θϢ̯ΜΊχΘ ̽ιΊχ͋ιΊ̯ (!ΡΆ) ι͋̽Ϊ΢΢͋Σ͇̯χΊΪΣν΂͟ Ϊι νΊ΢ΊΜ̯ι ϭ̯ιΊ̯Σχν χ·͋ι͋Ϊ͕΂ ̯ι͋ ι͕͋͋ι͋Σ̽͋ν χΪ Σ̯χΊΪΣ̯Μ ambient water quality criteria recommendations for human health.

Problem Fo rmulation

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 process. The structure of this criteria document is consistent with U.S.

E ́!͛ν · Framework for Human Health Risk Assessment to Inform Decision Making ͛ (USEPA,

2012 b ).

In the development of AWQC, EPA currently follows the deterministic assessment methodology outlined in E ́!͛ν · Methodology for Deriving Ambient Water Quality Criteria for the Protection of Human Health (2000) ͛ (USEPA, 2000), hereafter known as the 2000 Methodology. For the development of criteria for carcinogens that express a non-threshold,

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linear dose response, the 2000 Methodology takes into consideration exposure factors (body weight, drinking water intake, fish consumption, and bioaccumulation), the increased cancer risk due to exposure to the pollutant, and a 10 -6 (or 1 in 1,000,000) risk level for the general population. The 10 -6 risk level utilized in the derivation of the AWQC represents the water ̽ΪΣ̽͋Σχι̯χΊΪΣ χ·̯χ ϮΪϢΜ͇ ̼͋ ͋ϳζ͋̽χ͇͋ χΪ ΊΣ̽ι̯͋ν͋ ̯Σ ΊΣ͇ΊϭΊ͇Ϣ̯Μ͛ν ΜΊ͕͋χΊ΢͋ cancer risk from exposure to the particular pollutant by no more than one chance in one million, regardless of the additional lifetime cancer risk due to exposure, if any, to that particular substance from other sources. States and authorized tribes may consider adjusting exposure assumptions and related model inputs according to guidance in the 2000 Methodology, to assure that subpopulations are adequately protected if data are available.

Criteria Fo rmulas- Analysis Plan

The following formulas are used to develop E ́!͛ν Ρ! ΋͋̽χΊΪΣ 304(̯) human health ambient water quality criteria. EPA develops criteria for ambient waters typically considering two routes of exposure. The first formula can be used to derive a human health criterion that assumes exposure through both the consumption of water and the consumption of aquatic organisms. The second formula can be used to derive a criterion that assumes exposure through the consumption of aquatic organisms, but not water. The use of one criterion over the other depends on the designated use of the water bodies in question (i.e. drinking water source and/or fishable waters).

EPA recommends inclusion of 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 assure that this designated use can be protected and maintained. (2) Although rare, there are some public water supplies that provide drinking water from surface water sources without treatment. (3) Even among the majority of water supplies that do treat surface waters, existing treatments may not necessarily be effective for reducing levels of particular contaminants. (4) ͜Σ ̽ΪΣνΊ͇͋ι̯χΊΪΣ Ϊ͕ χ·͋ !ͽ͋Σ̽Θ͛ν ͽΪ̯Μν Ϊ͕ pollution prevention, ambient waters should not be contaminated to a level where the burden of achieving health objectives is shifted away from those responsible for pollutant discharges and placed on downstream users to bear the costs of upgraded or supplemental water treatment (USEPA, 2000).

EPA recommends the organism only criterion in those cases where the designated uses of a water body include only supporting fishable uses under Section 101(a) of the CWA, and thus, fish or shellfish for human consumption, but not as a drinking water supply source (e.g., non-potable estuarine waters) (USEPA, 2000).

3The formulas for deriving the criteria values are as follows (USEPA, 2000):

For consumption of water and organisms:

AWQC (μg/L) = [10 -6 * / CSF (kg·d/mg)] × BW (kg) × 1000 (μg/mg) † (Eq. 1)

4 DI (L/d) + ∑ (F · Ί (Ιͽ / ͇) ∓ !F Ί (ͫ Ιͽ)) Ί 2

For consumption of organisms only:

AWQC (μg/L) = [10 -6 * / CSF (kg·d/mg)] × BW (kg) × 1000 (μg/mg) † (Eq. 2)

∑ i 2 (F· Ί (Ιͽ / ͇) ∓ !F Ί (ͫ Ιͽ))

The fo llowing sections identify ea ch of the components of the formulas for the human

health ambient water quality c riteria and provide reference sources, previously u sed values

when available, and the values to be used in the updated criteria. Isophorone 78

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Where: AWQC = ambient water quality criteria (at the 10 -6 risk level) CSF = cancer slope factor BW = body weight DI = drinking water intake ∑ 4 νϢ΢΢̯χΊΪΣ Ϊ͕ ϭ̯ΜϢ͋ν ͕Ϊι ̯θϢ̯χΊ̽ χιΪζ·Ί̽ Μ͋ϭ͋Μν (Αͫ) Ϯ·͋ι͋ χ·͋ Μ͋χχ͋ι ͞Ί͟ νχ̯Σ͇ν ͕Ϊι χ·͋

i=2 trophic levels to be considered, starting with TL 2 and proceeding to TL 4

FCR i = fish consumption rate for aquatic trophic levels 2, 3, and 4

BAF i = bioaccumulation factor for aquatic trophic levels 2, 3, and 4

Exposure Factors:

Body W eight

The upd ated recommended body weight (BW) is 80 kg which represents the mean weight for adults 21 years of age and older. Α·Ίν ι͋̽Ϊ΢΢͋Σ͇̯χΊΪΣ Ίν ͕ΪϢΣ͇ ΊΣ E ́!͛ν · Exposure
F̯̽χΪιν H̯Σ͇̼ΪΪΙ ́ 2011 E͇ΊχΊΪΣ͛ in Chapter 8. It was based on data derived from the National Health and Nutrition Examination Survey (NHANES) 1999

− 2006 (USEPA, 2011). This body weight replac es the recommended standard weight for adults of 70 kg that was described in the 2000 Methodology which was approximated from the mean body weight of adults from the National Health and Nutrition Examination Survey (NHANES) III database (1988-1994) and a 1989 study by the National Cancer Institute (USEPA, 2000).

* 10 -6 or 1 in 1,000,000 risk level for the general population

† 1000 μg/mg is used to convert the units of mass into micrograms from milligrams.

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Drinking Water Intake

T he updated drinking water intake (DI) is 3 L/day, rounded from 3.091 L/day for consumer-only estimates of direct and indirect water ingestion based on NHANES 2003-2006

data for all sources of water at the 90 th ζ͋ι̽͋ΣχΊΜ͋ ͕Ϊι ̯͇ϢΜχν (≥21 Θ̯͋ιν of age) (USEPA, 2011). Direct water is defined as water ingested directly as a beverage (from all sources); indirect

wa ter is defined as water added in the preparation of food or beverages, not including indirect consumption of bottled water. This recommended value Ίν ͕ΪϢΣ͇ ΊΣ E ́!͛ν · Exposure Factors
H̯Σ͇̼ΪΪΙ ́ 2011 E͇ΊχΊΪΣ͛ in Table 3- 36. It replac es the drinking water intake standard of 2 L/day described in the 2000 Methodology which represented the 86 th percentile for adults 20 years ̯Σ͇ ΪΜ͇͋ι ΊΣ χ·͋ Ε΋ D͋ζ̯ιχ΢͋Σχ Ϊ͕ !ͽιΊ̽ϢΜχϢι͋͛ν 1994 -96 Continuing Survey of Food Intake by Individuals (CSFII) analysis or the 88 th percentile of adults in the National Cancer Institute study of the 1977-78 Nationwide Food Consumption Survey (USEPA, 2000).

Fish Consumption Rate

The updated fish consumption rate (FCR) for the general adult population is 22 grams/day (0.022 kg/day) (USEPA, 2014: see Table 9a ). It represents the 90 th percentile per capita consumption rate of freshwater and estuarine fish for the U.S. adult population 21 years of age and older based on the Centers for Disease Control and Prevention (CDC) National Health and Nutrition Examination Surveys (NHANES) conducted from 2003-2010. It replaces the FCR default of 17.5 grams/day, which represented an estimate of the 90th percentile per capita consumption rate of freshwater and estuarine fish for the U.S. adult population based on the Ε ̈́΋ ̈́ D͋ζ̯ιχ΢͋Σχ Ϊ͕ !ͽιΊ̽ϢΜχϢι͋͛ν (Ε΋D!͛ν) ΪΣχΊΣϢΊΣͽ ΋Ϣιϭ͋Θ Ϊ͕ FΪΪ͇ ͜Σχ̯Ι͋ ̼Θ ͜Σ͇ΊϭΊ͇Ϣ̯Μν (CSFII) 1994-96 data (USEPA, 2002a).

As recommended in the 2000 Methodology, this update to the criteria distinguishes a trophic level (TL) breakdown of the fish consumption rate to provide a better representation of ͇Ί͋χ̯ιΘ ͋ϳζΪνϢι͋ χΪ ͕Ίν· ̯χ ΢ϢΜχΊζΜ͋ χιΪζ·Ί̽ Μ͋ϭ͋Μν ̈́ !Σ Ϊιͽ̯ΣΊν΢͛ν χιΪζ·Ί̽ ζΪνΊχΊΪΣ ΊΣ χ·͋ ̯θϢ̯χΊ̽ food web can have an important effect on the magnitude of bioaccumulation of certain chemicals. The trophic levels are numbered 2, 3, and 4 and 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 fish.

In order to derive the trophic level breakdown of the 22 grams/day freshwater and estuarine FCR, the trophic level specific freshwater and estuarine FCR data sets for adults 21 years of age and older were identified (USEPA, 2014: see Tables 16a, 17a, and 18a ). In each χιΪζ·Ί̽ Μ͋ϭ͋Μ νζ͋̽Ί͕Ί̽ ͇̯χ̯ ν͋χ΂ χ·͋ ι̯χΊΪ Ϊ͕ χ·̯χ χιΪζ·Ί̽ Μ͋ϭ͋Μ͛ν 90 th percentile FCR compared to the summation of all three trophic level specific 90 th percentile FCRs was applied to the 22 grams/day FCR used in this update. The trophic level ratios were calculated as follows: TL ratio

= 90 th percentile FCR for the TL divided by the sum of the 90 th percentile FCRs for all TLs. TL2 = 7.6/21.3 = 0.3568 (35.68%), TL3 = 8.6/21.3 = 0.4038 (40.38%), and TL4 = 5.1/21.3 = 0.2394 (23.94%). Applying these ratios to the updated FCR of 22 grams/day result in trophic level breakdowns of TL2 = 8 grams/day (0.008 kg/day); TL3 = 9 grams/day (0.009 kg/day); and TL4 = 5

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grams/day (0.005 kg/day). These resulting trophic level FCRs are well within the confidence ΊΣχ͋ιϭ̯Μν ͕Ϊι ̯͋̽· Ϊ͕ χ·͋ χιΪζ·Ί̽ Μ͋ϭ͋Μ νζ͋̽Ί͕Ί̽ ͇ΊνχιΊ̼ϢχΊΪΣν͛ 90 th percentiles and add to the total of 22 grams/day (USEPA, 2014).

Bioaccumulation Factor

Several attributes of the bioaccumulation process are important to understand when deriving national BAFs for use in setting national 304(a) criteria. First, the term ̼͞ΊΪ̯̽̽Ϣ΢ϢΜ̯χΊΪΣ͟ ι͕͋͋ιν χΪ χ·͋ Ϣζχ̯Ι͋ ̯ nd retention of a chemical by an aquatic organism

from ̯ΜΜ νϢιιΪϢΣ͇ΊΣͽ ΢͇͋Ί̯ (͋ ̈́ͽ ̈́΂ Ϯ̯χ͋ι΂ ͕ΪΪ͇΂ ν͇͋Ί΢͋Σχ) ̈́ Α·͋ χ͋ι΢ ̼͞ΊΪ̽ΪΣ̽͋Σχι̯χΊΪΣ͟ ι͕͋͋ιν χΪ 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 magnitude of bioaccumulation by aquatic organisms can be substantially greater than the magnitude of bioconcentration. Thus, an assessment of bioconcentration alone may underestimate the

extent of accumulation in ̯θϢ̯χΊ̽ ̼ΊΪχ̯ ͕Ϊι χ·͋ν͋ ̽·͋΢Ί̯̽Μν ̈́ !̽̽Ϊι͇ΊΣͽΜΘ΂ E ́!͛ν ͽϢΊ͇͋ΜΊΣ͋ν presented in the 2000 Methodology emphasize the measurement or estimation of chemical bioaccumulation by aquatic organisms (USEPA, 2000).

The bioaccumulation factors (BAF) have ̼͋͋Σ ͋νχΊ΢̯χ͇͋ ϢνΊΣͽ E ́!͛ν EνχΊ΢̯χΊΪΣ  ́ιΪͽι̯΢ ͜Σχ͋ι͕̯̽͋ (E ́͜) ΋ϢΊχ͋ (Ε΋E ́!΂ 2012̯) ̈́ Α·͋ F!FTM ζιΪͽι̯΢ ϮΊχ·ΊΣ E ́͜ ΋ϢΊχ͋ estimates fish bioaccumulation factors using octanol-water partition coefficients (K OW ) and biotransformation data from a model designed by Arnot and Gobas (2003)

. The 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 metabolic 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 requires the octanol-water partition coefficient (K OW ) of the chemical and the normalized whole-body metabolic biotransformation rate constant as input parameters to predict BAF values. Model predictions may be highly uncertain for chemicals that have estimated log K OW values > 9. The model is not recommended at this time for chemicals that appreciably ionize, for pigments and dyes, or for perfluorinated substances (USEPA, 2012a).

For isophorone

, BAFs have been estimated using the EPI Suite model (USEPA, 2012 a) as described above for trophic levels 2, 3, and 4. The estimated lower (TL2), mid (TL3), and upper (TL4) trophic level BAFs for isophorone (log K OW = 1.70 ) are 3.301 L/kg, 3.493 L/kg, and 3.992 L/kg wet-weight, respectively. These estimated BAFs replace the bioconcentration factor (BCF) of 4.38 L/kg used in the 2002 criteria derivations, which was calculated from a measured steady-state bioconcentration study of bluegills and represented all trophic levels (USEPA, 1980).

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Hazard Identification and Dose Response: Cancer Slope Factor

Isophorone is characterized as a class C possible human carcinogen following the 1986 EPA Guidelines for Carcinogen Risk Assessment (USEPA, 1986a; USEPA, 1986b; USEPA, 1992).

The cancer slope factor (CSF) is an upper bound, approximating a 95% confidence limit, on the increased cancer risk from a lifetime oral exposure to an agent. The CSF for isophorone

is 9.5 × 10 – 4 per mg/kg·day (0.00095 per mg/kg·day) (USEPA, 1992).

The principle study by National Toxicology Program (NTP, 1986) chosen to calculate the cancer slope factor for isophorone was based on development of preputial gland carcinomas in male rats orally exposed to isophorone (USEPA, 1992).

Criteria Derivation- Analysis

Table 1 summarizes model inputs used to derive the 2014 updated human health ambient water quality criteria for isophorone. Criteria calculations are presented below. These updated isophorone criteria recommendations are based on the 2000 Methodology and updated exposure assumptions as described above (Exposure Factors).

Table 1. Summary of input parameters for 2014 human health ambient water quality criteria for isophorone

Component Value Source Input Characterization

CSF 0.00095 per mg/ kg·day USEPA,

1992 an upper bound, approximating a 95% confidence limit, on the increased cancer risk from a lifetime exposure to an agent by ingestion

BW 80 kg USEPA,

2011 mean weight for adults (≥21 Θ̯͋ιν Ϊ͕ ̯ͽ͋)

DI 3 L/day USEPA,

2011 90 th ζ͋ι̽͋ΣχΊΜ͋ ͕Ϊι ̯͇ϢΜχν (≥21 Θ̯͋ιν of age)

FCR TL2 0.00 8 kg/day USEPA

, 2014 90 th percentile consumption rate for the U.S.

adult ζΪζϢΜ̯χΊΪΣ (≥21 Θ̯͋ιν Ϊ͕ ̯ͽ͋) TL3 0.00 9 kg/day

TL4 0.00 5 kg/day

BAF TL2 3.301 L/kg USEPA,

2012a EPI Suite K OW model estimated steady

- state
BAF values for non

- ionic organic chemicals in 3 general trophic levels of fish in temperate environments (10°C) TL3 3.493 L/kg

TL4 3.992 L/kg

For consumption of water and organisms:

7 AWQC (μg/L) = [10 -6 / CSF (kg·d/mg)] × BW (kg) × 1000 (μg/mg)

4 DI (L/d) + ∑ (F· Ί (Ιͽ ͇) ∓ !F Ί (ͫ / Ιͽ))

Ί = 2= 10 -6 / 0.00095 kg·d/mg × 80 kg × 1000 μg/mg 3 L/d + ((0.008 kg/d × 3.301 L/kg) + (0.009 kg/d × 3.493 L/kg) + (0.005 kg/d × 3.992 L/kg))

= 27. 360 μg /L (rounded to 27 μg/L because of significant figures, see 2000 Methodology)

AWQC (μg/L) = [10 -6 / CSF (kg·d/mg)] × BW (kg) × 1000 (μg/mg)

4 ∑ (F· Ί (Ιͽ ͇) ∓ !F Ί (ͫ Ιͽ))

Ί 2

= 10 -6 / 0.00095 kg·d/mg × 80 kg × 1000 μg/mg

(0.008 kg/d × 3.301 L/kg) + (0.009 kg/d × 3.493 L/kg) + (0.005 kg/d × 3.992 L/kg)

= 1,082

. 328/ μg /L (rounded to 1,100 μg/L because of significant figures, see 2000 Methodology) / /

= Isophorone 78

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For consumption of organisms only:

The updated magnitude of the human health ambient water quality criteria for

i sophorone at the 10 -6 risk level are 27 μg/L (water and organism) and 1,100 μg/L (organism only) (Table 2). These updated criteria replace the previously published values (USEPA, 2002b).

Table 2. ΋Ϣ΢΢̯ιΘ Ϊ͕ E ́!͛ν ζι͋̽ΊΪϢνΜΘ ι͋̽Ϊ΢΢͋Σ͇͇͋ (2002 ) and updated (2014) human health ambient water quality criteria for isophorone

2002 Human Health AWQC 2014 Human Health AWQC Water and Organism 35 μg/L 27 μg/L Organism Only 960 μg/L 1,100 μg/L

These AWQC are meant to be protective of human health for the general adult population from an increased cancer risk due to exposure to isophorone at a 10 -6 or 1 in 1,000,000 risk level. The 10 -6 risk level associated with the AWQC represents the concentration χ·̯χ ϮΪϢΜ͇ ̼͋ ͋ϳζ͋̽χ͇͋ χΪ ΊΣ̽ι̯͋ν͋ ̯Σ ΊΣ͇ΊϭΊ͇Ϣ̯Μ͛ν ΜΊ͕͋χΊ΢͋ ̯̽Σ̽͋ r risk from exposure to the particular pollutant by no more than one chance in one million, regardless of the additional lifetime cancer risk due to exposure, if any, to that particular substance from other sources.

Criteria Characterization

The update d 2014 human health AWQC for isophorone take into account current data on health effects and exposure input parameters, consistent with the 2000 Methodology. The updated 2014 human health AWQC for isophorone are less than a factor of two from E ́!͛ν previously recommended 2002 criteria; i.e. the water-and-organism criterion decreased from

35 to 27 μg/L and the organism-only criterion increased from 960 to 1,100 μg/L (Table 2). The following paragraphs describe the individual influence of each of the revised model inputs and exposure assumptions on the overall change in value.

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Body Weight

E ́!͛ν updated AWQC assume a higher body weight compared to the previously recommended 2002 criteria, reflecting a recent rise in average adult body weight among the

U.S. population. The updated body weight assumption of 80 kg based on recent survey data

from the 1999

− 2006 NHANES data is 10 kg greater than the previous recommendation of 70 kg. Assuming all other input parameters remain constant, a higher average body weight in the AWQC calculations (Eq. 1 and 2 above) results in higher AWQC. That is, as body weight 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 drinking water intake assumption is 3 L/day, which is higher than the previously recommended rate of 2 L/day. Assuming all other input parameters remain constant, a higher drinking water intake assumption in the AWQC calculations (Eq. 1 and 2 above) results in lower AWQC. That is, as drinking water intake 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 fish consumption rate is 22 g/day, divided into trophic level rates of 8 g/day, 9 g/day, and 5 g/day for trophic levels 2, 3, and 4, respectively, which is higher than the previously recommended rate of 17.5 g/day. Assuming all other input parameters remain constant, a higher fish consumption rate assumption in the AWQC calculations (Eq. 1 and 2 above) results in lower AWQC. That is, as fish consumption increase, 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 EPI Suite model-estimated BAFs rather than the previously recommended BCF of 4.38 L/kg. The lower (TL2), mid (TL3), and upper (TL4) trophic level BAFs assumed in the updated criteria equations (Eq. 1 and 2 above) are 3.301, 3.493, and 3.992 L/kg wet-weight, respectively. Assuming all other input parameters remain constant, the lower ratios of fish tissue concentrations to water concentrations of isophorone by aquatic organisms result in higher AWQC. That is, as bioaccumulation or bioconcentration of a contaminant in fish and shellfish decreases, and thus overall exposure decreases, the level of a contaminant in water at or below which negative health effects are not anticipated from a lifetime of exposure

increases. The utilization of a bioaccumulation factor rather than a bioconcentration factor better represents the amount of a contaminant accumulating in an organism because it ̯̽̽ΪϢΣχν ΣΪχ ΪΣΜΘ ͕Ϊι χ·͋ Ϊιͽ̯ΣΊν΢͛ν ͋ϳζΪνϢι͋ χΪ χ·͋ ζΪΜΜϢχ̯Σχ ΊΣ χ·͋ Ϯ̯χ͋ι ̽ΪΜϢ΢Σ΂ ̼Ϣχ also from the food chain and surrounding environment as well as biotransformation of the pollutant

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in the organism due to metabolic processes. The utilization of the three trophic levels of fish and shellfish consumed, as opposed to representing all trophic levels of fish and shellfish consumed by a single value, allows for better exposure representation, especially when pollutants bioaccumulate in significantly different amounts for organisms in different trophic levels at different positions in the food chain.

Additional routes of exposure to a particular pollutant besides exposure from water intake and fish consumption are possible and may be considered when setting criteria for a state or tribe. Possible additional routes include, but are not limited to, dermal exposure, inhalation exposure, marine fish and shellfish consumption (when not included in the fish consumption rate), and non-fish dietary exposures (fruits, vegetables, grains, meats or poultry). If scientific evidence exists which indicate that one or more of these routes pose a significant risk of exposure, states and authorized tribes are encouraged to ensure that subpopulations are adequately protected.

States, territories, and authorized tribes have the flexibility to develop criteria, on a sitespecific basis, that provide additional protection appropriate for highly exposed populations. EPA is aware that exposure patterns in general, and fish consumption in particular, vary substantially. EPA understands that highly exposed populations may be widely distributed geographically throughout a given state, territory, or authorized tribal area. EPA recommends that priority be given to identifying and adequately protecting the most highly exposed populations. Thus, if a state, territory, or authorized tribe determines that a highly exposed population is at greater risk and would not be adequately protected by criteria based on the general population, and by the national 304(a) criteria in particular, the state, territory, or authorized tribe may adopt more stringent criteria using alternative exposure assumptions (USEPA, 2000). Subpopulations that may be considered include, but are not limited to, recreational fishers, subsistence fishers, women of childbearing age, and children. When scientific data exist showing one of these subpopulations is at risk of greater exposure to the pollutant or are biologically more sensitive, then the relevant inputs should be considered in setting criteria. This could entail raising the fish consumption rate to a level more reflective of the subpopulation based on collected data or adjusting the body weight and drinking water

intake.

Chemical Name / Synonyms

 Isophorone (CAS Number 78- 59

- 1)

 Isoacetophorone

 Isoforon

 Isophoron

 alpha-Isophoron

 alpha-Isophorone

 3,5,5-Trimethyl-2-cyclohexenone

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References

N TP (National Toxicology Program). 1986. Toxicology and carcinogenesis studies of isophorone (CAS No. 78- 59 -1) in F344/N rats and B6C3F1 mice (gavage studies). NTP TR-29l. NIH

Pub. No. 86-2547.

USEPA (U.S. Environmental Protection Agency). 1980. Ambient Water Quality Criteria for Isophorone. Office of Water. Washington, DC. EPA- 440 -5- 80 -056. http://water.epa.gov/scitech/swguidance/standards/upload/2001_10_12_criteria_ambi entwqc_isophorone80.pdf

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USEPA (U.S. Environmental Protection Agency). 1986a. Guidelines for Carcinogen Risk

Assessment. Federal Register 51: 33992-34003.

USEPA (U.S. Environmental Protection Agency). 1986b. Guidelines for Carcinogen Risk Assessment. Risk Assessment Forum. Washington, DC. EPA- 630 -R- 00 -004. http://www.epa.gov/raf/publications/pdfs/CA%20GUIDELINES_1986.PDF

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USEPA (U.S. Environmental Protection Agency). 1992. Isophorone (CASRN 78- 59 -1). Integrated Risk Information System . Retrieved 10 July 2013. http://www.epa.gov/iris/subst/0063.htm

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USEPA (U.S. Environmental Protection Agency). 2000. Methodology for Deriving Ambient Water Quality Criteria for the Protection of Human Health. Office of Water. Washington, DC.

EPA- 822 -B- 00

- 004. http://water.epa.gov/scitech/swguidance/standards/upload/2005_05_06_criteria_hum anhealth_method_complete.pdf

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USEPA (U.S. Environmental Protection Agency). 2002a. Estimated Per Capita Fish Consumption in the United States. Washington, DC. EPA- 821 -C- 02 -003. http://water.epa.gov/scitech/swguidance/standards/criteria/health/upload/consumpti on_report.pdf

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USEPA (U.S. Environmental Protection Agency). 2002b. National Recommended Water Quality Criteria: 2002. Office of Water. Washington, DC. EPA- 822 -R- 02 -047. http://water.epa.gov/scitech/swguidance/standards/upload/2008_04_29_criteria_wqct able_nrwqc-2002.pdf

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USEPA (U.S. Environmental Protection Agency). 2011. Exposure Factors Handbook: 2011 Edition. Office of Research and Development. Washington, DC. EPA-600-R- 09 -052F. http://www.epa.gov/ncea/efh/pdfs/efh-complete.pdf

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USEPA (U.S. Environmental Protection Agency). 2012̯ ̈́ EνχΊ΢̯χΊΪΣ  ́ιΪͽι̯΢ν ͜Σχ͋ι͕̯̽͋ ΋ϢΊχ͋TM for Microsoft® Windows, v 4.10. United States Environmental Protection Agency, Washington, DC, USA. http://www.epa.gov/oppt/exposure/pubs/episuite.htm

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USEPA (U.S. Environmental Protection Agency). 201 2b

. Framework for Human Health Risk Assessment to Inform Decision Making

. Office of the Science Advisor. Washington, DC.

EPA- 601 -D- 12 -001. http://www.epa.gov/raf/files/framework-document-7- 13 -12.pdf

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USEPA (U.S. Environmental Protection Agency). 2014. Estimated Fish Consumption Rates for the U.S. Population and Selected Subpopulations (NHANES 2003-2010). Office of Water. Washington, DC. EPA- 820 -R- 14

- 002.

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