CHEMICAL UPDATE WORKSHEET

Chemical Name: Cyclohexanone CAS #: 108-94-1 Revised By: RRD Toxicology Unit

Revision Date: August 17, 2105

(A) Chemical-Physical Properties Part 201 Value Updated Value Reference Source Comments

Molecular Weight (g/mol) 98.14 98.15 EPI EXP

Physical State at ambient temp Liquid Liquid MDEQ

Melting Point (˚C) --- -31.00 EPI EXP

Boiling Point (˚C) 155.4 155.40 EPI EXP

Solubility (ug/L) 2.30E+7 2.5000E+07 EPI EXP

Vapor Pressure (mmHg at 25˚C) 4.8 4.33E+00 EPI EXP

HLC (atm-m³/mol at 25˚C) 7.80 9.00E-06 EPI EXP

Log Kow (log P; octanol-water) 0.81 0.81 EPI EXP

Koc (organic carbon; L/Kg) 6.26 17.38 EPI EST

Ionizing Koc (L/kg) NR NA NA

Diffusivity in Air (Di; cm2/s) 0.08 7.68E-02 W9 EST

Diffusivity in Water (Dw; cm2/s) 8.0E-6 9.3792E-06 W9 EST

Soil Water Partition Coefficient (Kd; inorganics) NR NR NA NA

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Part 201 Value Updated Value Reference Source Comments

Flash Point (˚C) 146 F 44 CRC EXP

Lower Explosivity Level (LEL; unit less) NA 0.011 CRC EXP

Critical Temperature (K) 665 CRC EXP

Enthalpy of Vaporization (cal/mol) NA NA NA

Density (g/mL, g/cm3) 0.9478 CRC EXP

EMSOFT Flux Residential 2 m (mg/day/cm2) 2.71E-05 1.81E-05 EMSOFT EST

EMSOFT Flux Residential 5 m (mg/day/cm2) 6.67E-05 2.29E-05 EMSOFT EST

EMSOFT Flux Nonresidential 2 m (mg/day/cm2) 3.87E-05 2.54E-05 EMSOFT EST

EMSOFT Flux Nonresidential 5 m (mg/day/cm2) 9.49E-05 2.91E-05 EMSOFT EST

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(B) Toxicity Values/Benchmarks Part 201 Value Updated Value Source/Reference/

Date Comments/Notes

/Issues Reference Dose (RfD) (mg/kg/day) 4.5E+0 2.0E-1

PPRTV, 2010/ MDEQ, 2015

RfD details

Chronic rat drinking water study (Lijinsky & Kovatch, 1986) NOAEL=3300 ppm adj. to 4488 mg/kg; Critical effect = body weight depression. UF=100. CCD/RRD date: 9/02/1986

Tier 2 Source: PPRTV: Basis: PPRTV is a more current evaluation. This RfD is a modified value of the PPRTV sub chronic RfD = 2.0 mg/kg-day. An additional UF of 10 to account for sub chronic to chronic extrapolation is added to the composite UF of 300. PPRTV: Per PPRTV (9/15/2010), sub chronic p-RfD = 2 mg/kg-day Critical Study: Lijinsky, W; Kovatch, RM. (1986) Chronic toxicity study of cyclohexanone in rats and mice (NCI study). J Natl Cancer Inst 77: 941–949. Method(s): F344 rats (5/sex/dose group) were exposed to cyclohexanone in acidified drinking water at 190, 400, 800, 1600, 3300, 4700, or 6500 ppm for 25 weeks (Lijinsky and Kovatch, 1986; NCI, 1979). Water was acidified to suppress bacterial growth. An additional group of 5 rats (number/sex not specified) served as the untreated control group. The estimated doses are 0, 30, 62, 124, 249, 513, 731, and 1010 mg/kg-day for males, and 0, 32, 68, 135, 271, 559, 796, and 1100 mg/kg-day for females based on water intake rates of 0.156 and 0.169 L/day for males and females, respectively. Critical effect: decreased body-weight gain in male rats End point or Point of Departure (POD): NOAEL = 731 mg/kg-day Uncertainty Factors: UF = 300 (10 each for interspecies variability and interspecies extrapolation, and 3 for database deficiencies). Data for evaluating reproductive toxicity are inadequate and limited. Source and date: PPRTV, 9/15/2010 Tier 1 and 2 Sources: IRIS: RfD = 5.0 mg/kg-day (1987): Critical Study: Lijinsky, W. and M. Kovatch. 1986. A chronic toxicity study of cyclohexanone in rats and mice (NCI study). J. Natl. Cancer Inst. 77(4): 941-9. Method(s): F344 rats and B6C3F1 mice (52/sex/grp) were exposed to cyclohexanone in drinking water at 3,300 or 6,500 ppm (rats), 6,500 or 13,000

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CHEMICAL UPDATE WORKSHEET Cyclohexanone (108-94-1)

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Part 201 Value Updated Value Source/Reference/Date

Comments/Notes/Issues

ppm (male mice), or 6,500, 13,000 or 25,000 ppm (female mice) for 2 years. Based on EPA (1988) reference values for body weight and water consumption of F344 rats in a chronic study, using water intake factors of 0.129 and 0.144 L/day for males and females respectively, the estimated doses are 0, 426, and 838 mg/kg-day for males and 0, 476, and 937 mg/kg-day for females. Critical effect: Decreased weight gain End point or Point of Departure (POD): NOAEL = 3300 ppm cyclohexanone (converted to 462 mg/kg/day) in rats. Uncertainty Factors: UF = 100 (10 each for interspecies variability and interspecies extrapolation) Source and date: IRIS, Last revision date - 9/30/1987. An EPA screening-level review conducted in 2002 did not identify any critical new studies. MRL: No MRL record available at this time. Tier 3 Source: MDEQ: Per DEQ-CCD/RRD (9/02/1986), RfD = 4.5 mg/kg-day. See Part 201 Value RfD details. This RfD is a modified value of the 1987 IRIS RfD.

Oral Cancer Slope Factor (CSF) (mg/kg-day)-1)

-- NA MDEQ, 2015

CSF details NA

Carcinogen Weight-of-Evidence (WOE) Class: “Inadequate Information to Assess [the] Carcinogenic Potential” of cyclohexanone. IRIS WOE Basis: The only available studies that evaluated the carcinogenic potential of cyclohexanone were the 2-year drinking water studies in rats and mice conducted by Lijinsky and Kovatch (1986). Lijinsky and Kovatch (1986) concluded that the evidence of carcinogenic activity is marginal, and the effect, if any, is weak. Source and Date: PPRTV, 9/15/2010 Tier 1 and 2 Sources: IRIS: Per IRIS (9/30/1987), no value at this time. IRIS has not evaluated cyclohexanone for evidence of human carcinogenic potential. PPRTV: Per PPRTV (9/15/2010), no value at this time.

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Part 201 Value Updated Value Source/Reference/Date

Comments/Notes/Issues

MRL: NA; MRLs are for non-cancer effects only. Tier 3 Source: MDEQ: Per DEQ-CCD, no value at this time.

Reference Concentration (RfC) or Initial Threshold Screening Level (ITSL) (µg/m³)

1.0E+3 7.0E+2 PPRTV, 2010

RfC/ITSL details

ITSL generated under July 1992 interim process for calculation of ITSL, based on 1% of TLV. CCD/AQD date: 9/15/1992

Tier 2 Source: PPRTV: Basis: PPRTV is the only available value. PPRTV provisional RfC = 7.0E+2 µg/m³: Critical Study: Treon, JF; Crutchfield, WE, Jr; Kitzmiller, KV. (1943) The physiological response of animals to cyclohexane, methylcyclohexane, and certain derivatives of these compounds. J Ind Hyg Toxicol 25:323–346. Method(s): Groups of four rabbits (sex not specified) were exposed by inhalation to 0 (untreated), 0 (sham-exposed), 190, 309, 773, 1414, or 3082 ppm (converted by EPA to 0, 763, 1241, 3103, 5677, or 12,373 mg/m3) of cyclohexanone vapor, 6 hours/days, 5 days/week, for 3 weeks (for the highest dose level only, 12,373 mg/m3) or 10 weeks (all other groups). In addition to the rabbits, one Rhesus monkey was exposed to 608 ppm (2441 mg/m3) by the same schedule for 10 weeks. Evaluation for clinical signs was done during exposure and up to 2 months after exposure termination. Critical effect: adverse clinical signs in rabbits End point or Point of Departure (POD): NOAELHEC = 222 mg/m3 Uncertainty Factors: UF = 300 (10 each for interspecies variability and use of a sub chronic study, and 3 for interspecies extrapolation) Source and date: PPRTV, 9/15/2010 Tier 1 and 2 Sources: IRIS: Per IRIS (9/30/1987), no value at this time. MRL: No MRL record available at this time.

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Part 201 Value Updated Value Source/Reference/Date

Comments/Notes/Issues

Tier 3 Source: MDEQ: Per DEQ-CCD/AQD (12/05/2012), ITSL = 800 = 8E+2 µg/m³. See Part 201 Value RfC details.

Inhalation Unit Risk Factor (IURF) ((µg/m3)-1)

-- NA MDEQ, 2015

IURF details NA

Carcinogen Weight-of-Evidence (WOE) Class: “Inadequate Information to Assess [the] Carcinogenic Potential” of cyclohexanone. IRIS WOE Basis: The only available studies that evaluated the carcinogenic potential of cyclohexanone were the 2-year drinking water studies in rats and mice conducted by Lijinsky and Kovatch (1986). Lijinsky and Kovatch (1986) concluded that the evidence of carcinogenic activity is marginal, and the effect, if any, is weak. Source and Date: PPRTV, 9/15/2010 Tier 1 and 2 Sources: IRIS: Per IRIS (9/30/1987), no value at this time. IRIS has not evaluated cyclohexanone for evidence of human carcinogenic potential. PPRTV: Per PPRTV (9/15/2010), no value at this time. MRL: NA; MRLs are for non-cancer effects only. Tier 3 Source: MDEQ: Per DEQ-CCD, no value at this time.

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Mutagenic Mode of Action (MMOA)? (Y/N)

-- NO USEPA, 2015

MMOA Details -- NA

Not listed as a carcinogen with mutagenic MOA in the USEPA OSWER List.

Developmental or Reproductive Effector? (Y/N)

No No. The RfD and ITSL are not based on a reproductive-

developmental effect.

MDEQ, 2015

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Part 201 Value Updated Value Source/Reference/Date

Comments/Notes/Issues

Developmental or Reproductive Toxicity Details

NA NA

State Drinking Water Standard (SDWS) (ug/L)

-- -- SDWA, 1976

SDWS details NA MI Safe Drinking Water Act (SDWA) 1976 PA 399

Secondary Maximum Contaminant Level (SMCL) (ug/L)

-- -- SDWA, 1976 and USEPA SMCL List,

2015

SMCL details NA SDWA, 1976 and USEPA SMCL List, 2015

Is there an aesthetic value for drinking water? (Y/N)

NO Not evaluated. NA

Aesthetic value (ug/L) NA NA NA

Aesthetic Value details NA NA

Phytotoxicity Value? (Y/N) NO Not evaluated. NA

Phytotoxicity details NA NA NA

Others

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(C) Chemical-specific Absorption Factors Part 201 Value Update Source/Reference/

Dates Comments/Notes

/Issues Gastrointestinal absorption efficiency value (ABSgi)

--- 1.0 MDEQ, 2015/USEPA RAGS-E, 2004

ABSgi details RAGS E (USEPA, 2004) Default Value

Skin absorption efficiency value (AEd)

--- 0.1 MDEQ, 2015

AEd details

Ingestion Absorption Efficiency (AEi)

1.0 MDEQ, 2015

AEi Details

Relative Source Contribution for Water (RSCW)

0.2 MDEQ, 2015

Relative Source Contribution for Soil (RSCS)

1.0 MDEQ, 2015

Relative Source Contribution for Air (RSCA)

1.0 MDEQ, 2015

Others

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(D) Rule 57 Water Quality Values and GSI Criteria Current GSI value (g/L) NA

Updated GSI value (g/L) NA

Rule 57 Drinking Water Value (g/L) NA

Rule 57 Value

(g/L) Verification Date

Human Non-cancer Values- Drinking water source (HNV-drink)

Human Non-Cancer Values- Non-drinking water sources (HNV-Non-drink)

Wildlife Value (WV)

Human Cancer Values for Drinking Water Source (HCV-drink)

Human Cancer values for non-drinking water source (HCV-Non-drink)

Final Chronic Value (FCV)

Aquatic maximum value (AMV)

Final Acute Value (FAV)

Sources: 1. MDEQ Surface Water Assessment Section Rule 57 website 2. MDEQ Rule 57 table

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(E) Target Detection Limits (TDL) Value Source

Target Detection Limit – Soil (g/kg) 2,500 MDEQ, 2015

Target Detection Limit – Water (g/L) 50 MDEQ, 2015

Target Detection Limit – Air (ppbv) 2.47E+02 MDEQ, 2015

Target Detection Limit – Soil Gas (ppbv) 8.23E+03 MDEQ, 2015

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CHEMICAL UPDATE WORKSHEET ABBREVIATIONS: CAS # - Chemical Abstract Service Number. Section (A) Chemical-Physical Properties Reference Source(s): CRC Chemical Rubber Company Handbook of Chemistry

and Physics, 95th edition, 2014-2015 EMSOFT USEPA Exposure Model for Soil-Organic Fate and

Transport (EMSOFT) (EPA, 2002) EPA2001 USEPA (2001) Fact Sheet, Correcting the Henry’s

Law Constant for Soil Temperature. Office of Solid Waste and Emergency Response, Washington, D.C.

EPA4 USEPA (2004) User’s Guide for Evaluating Subsurface Vapor Intrusion into Buildings. February 22, 2004.

EPI USEPA’s Estimation Programs Interface SUITE 4.1, Copyright 2000-2012

HSDB Hazardous Substances Data Bank MDEQ Michigan Department of Environmental Quality NPG National Institute for Occupational Safety and

Health Pocket Guide to Chemical Hazards PC National Center for Biotechnology Information’s

PubChem database PP Syracuse Research Corporation’s PhysProp database SCDM USEPA’s Superfund Chemical Data Matrix SSG USEPA’s Soil Screening Guidance: Technical

Background Document, Second Edition, 1996 USEPA/EPA United States environmental protection agency’s

Risk Assessment Guidance for Superfund Volume I: Human Health Evaluation Manual (Part E, Supplemental Guidance for Dermal Risk Assessment). July, 2004.

W9 USEPA’s User Guide for Water9 Software, Version 2.0.0, 2001

Basis/Comments: EST estimated EXP experimental EXT extrapolated NA not available or not applicable NR not relevant Section (B) Toxicity Values/Benchmarks Sources/References: ATSDR Agency for Toxic Substances and Disease Registry CALEPA California Environmental Protection Agency CAL DTSC California Department of Toxic Substances Control CAL OEHHA CAEPA Office of Environmental Health Hazard

Assessment CCD MDEQ Chemical Criteria Database ECHA European Chemicals Agency (REACH) OECD HPV Organization for Economic Cooperation and

Development HPV Database HEAST USEPA’s Health Effects Assessment Summary Tables IRIS USEPA’s Integrated Risk Information System MADEP Massachusetts Department of Environmental

Protection MDEQ/DEQ Michigan Department of Environmental Quality DEQ-CCD/AQD MDEQ Air Quality Division DEQ-CCD/RRD MDEQ Remediation and Redevelopment Division DEQ-CCD/WRD MDEQ Water Resources Division MNDOH Minnesota Department of Health

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NJDEP New Jersey Department of Environmental Protection

NYDEC New York State Department of Environmental Conservation

OPP/OPPT USEPA’s Office of Pesticide Programs PPRTV USEPA’s Provisional Peer Reviewed Toxicity Values RIVM The Netherlands National Institute of Public Health

and the Environment TCEQ Texas Commission on Environmental Quality USEPA United States Environmental Protection Agency USEPA OSWER USEPA Office of Solid Waste and Emergency

Response USEPA MCL USEPA Maximum Contaminant Level WHO World Health Organization WHO IPCS International Programme on Chemical Safety

(IPCS/INCHEM) WHO IARC International Agency for Research on Cancers NA Not Available. NR Not Relevant. Toxicity terms: BMC Benchmark concentration BMCL Lower bound confidence limit on the BMC BMD benchmark dose BMDL Lower bound confidence limit on the BMD CSF Cancer slope Factor CNS Central nervous system IURF or IUR Inhalation unit risk factor LOAEL Lowest observed adverse effect level LOEL Lowest observed effect level MRL Minimal risk level (ATSDR) NOAEL No observed adverse effect level NOEL No observed effect level

RfC Reference concentration RfD Reference dose p-RfD Provisional RfD aRfD Acute RfD UF Uncertainty factor WOE Weight of evidence Section (C) Chemical-specific Absorption Factors MDEQ Michigan Department of Environmental Quality USEPA RAGS-E United States Environmental Protection Agency’s

Risk Assessment Guidance for Superfund Volume I: Human Health Evaluation Manual (Part E, Supplemental Guidance for Dermal Risk Assessment). July, 2004.

Section (D) Rule 57 Water Quality Values and GSI Criteria GSI Groundwater-surface water interface NA A value is not available or not applicable. ID Insufficient data to derive value NLS No literature search has been conducted