Bromoform CAS #: 75-25-2 Revised By: RRD Toxicology Unit Revision Date: August 14, 2015

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Chemical Name: Bromoform CAS #: 75-25-2 Revised By: RRD Toxicology Unit Revision Date: August 14, 2015

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

Molecular Weight (g/mol) 252.8 252.73 EPI EXP

Physical State at ambient temp Liquid Liquid MDEQ

Melting Point (˚C) 281 8.00 EPI EXP

Boiling Point (˚C) 149.1 149.10 EPI EXP

Solubility (ug/L) 3.10E+6 3.10E+06 EPI EXP

Vapor Pressure (mmHg at 25˚C) 5.928 5.60E+00 PC EXP

HLC (atm-m³/mol at 25˚C) 5.35E-4 5.35E-04 EPI EXP

Log Kow (log P; octanol-water) 2.35 2.40 EPI EXP

Koc (organic carbon; L/Kg) 87.0 31.82 EPI EST

Ionizing Koc (L/kg) NR NA NA

Diffusivity in Air (Di; cm2/s) 0.0149 3.57E-02 W9 EST

Diffusivity in Water (Dw; cm2/s) 1.03E-5 1.0356E-05 W9 EST Soil Water Partition Coefficient NR NR NA NA (Kd; inorganics) CHEMICAL UPDATE WORKSHEET Bromoform (75-25-2)

Part 201 Value Updated Value Reference Source Comments

Flash Point (˚C) NA 83 CRC EXP Lower Explosivity Level (LEL; NA NA NA NA unit less) Critical Temperature (K) 6.96E+02 EPA2004 EXP

Enthalpy of Vaporization 9.48E+03 EPA2004 EXP (cal/mol) Density (g/mL, g/cm3) 2.8788 CRC EXP

EMSOFT Flux Residential 2 m 1.79E-05 2.59E-05 EMSOFT EST (mg/day/cm2) EMSOFT Flux Residential 5 m 2.35E-05 5.54E-05 EMSOFT EST (mg/day/cm2) EMSOFT Flux Nonresidential 2 m 2.35E-05 4.03E-05 EMSOFT EST (mg/day/cm2) EMSOFT Flux Nonresidential 5 m 2.82E-05 8.26E-05 EMSOFT EST (mg/day/cm2)

CHEMICAL UPDATE WORKSHEET Bromoform (75-25-2)

(B) Toxicity Values/Benchmarks Source*/Reference Comments/Notes Part 201 Value Updated Value /Date /Issues Reference Dose 1.8E-2 2.0E-2 ATSDR, 2005 (RfD) (mg/kg/day) Rat subchronic Tier 2 Source: oral gavage ATSDR: Complete bioassay (NTP, Basis: ATSDR is the best available chronic value and a more recent assessment 1989); NOAEL= than IRIS. 17.9 mg/kg/day. ATSDR (9/2005) oral chronic MRL = 0.02 mg/kg-day: UF=1000. Critical Critical Study: NTP. 1989a. Toxicology and carcinogenesis studies of effect = hepatic tribromomethane (bromoform) in F344/N rats and B6C3F1 mice (gavage studies). lesions. National Toxicology Program. Technical Report Series No. 350. Research Triangle Source: IRIS Park, NC: U.S. Department of Health and Human Services. MDEQ-CCD date: Method(s): F344/N rats (50/sex/group) were administered via gavage 0, 100, or 8/13/1987 200 mg/kg bromoform in corn oil 5 days/week for 103 weeks. Critical effect: histopathological changes (vacuolization) in the liver End point or Point of Departure (POD): LOAEL = 100 mg/kg; duration-adjusted LOAEL = 71 mg/kg/day RfD details Uncertainty Factors: UF = 300; MF = 10 (10 each for intraspecies variability and interspecies extrapolation, 3 for use of a LOAEL, and an MF of 10 for the identification of a lower LOAEL in the 13 week NTP study. Source and date: ATSDR, 9/2005. A Toxicological Profile is available.

Tier 1 and 2 Sources: IRIS: IRIS RfD = 2.0E-2 mg/kg/day Critical Study: NTP (National Toxicology Program). 1989. Toxicology and Carcinogenicity Studies of Tribromomethane and Bromoform in F344/N rats and B6C3F1 mice (gavage study). NTP-350. Research Triangle Park, NC. Method(s): Bromoform was administered by gavage to 1) F344/N rats (10/sex/dose) with 0, 12, 25, 50, 100, or 200 mg/kg, 2) B6C3F1 mice (10/sex/dose) with 0, 25, 50, 100, 200, or 400 mg/kg bromoform for 5 days/week for 13 weeks. Critical effect: increased clear cell foci of the liver in male rats End point or Point of Departure (POD): NOAEL = 25 mg/kg converted to 17.9

CHEMICAL UPDATE WORKSHEET Bromoform (75-25-2)

Source*/Reference Comments/Notes Part 201 Value Updated Value /Date /Issues mg/kg/day (duration-adjusted) Uncertainty Factors: UF = 1,000 (10 each for intraspecies variability, interspecies extrapolation, and use of subchronic study) Source and date: IRIS, Last revision date - 3/1/1991. EPA screening-level review in 2002 identified one or more significant new studies. PPRTV: PPRTV (4/14/2005) refers to IRIS RfD. A subchronic RfD of 0.03 mg/kg-day was derived: Critical Study: NTP 1989 (see IRIS value details) Method(s): (See IRIS value details) Critical effect: hepatocellular vacuolization in male rats

End point or Point of Departure (POD): duration-adjusted BMDL10 = 2.6 mg/kg- day Uncertainty Factors: UF = 100 (10 each for intraspecies variability and interspecies extrapolation) Source and date: PPRTV, 4/14/2005 MRL: Per ATSDR (9/2005), an intermediate oral MRL = 0.2 mg/kg-day was also derived: UF = 3,000 for hepatic effects: Critical Study: NTP. 1989a. Toxicology and carcinogenesis studies of tribromomethane (bromoform) in F344/N rats and B6C3F1 mice (gavage studies). National Toxicology Program. Technical Report Series No. 350. Research Triangle Park, NC: U.S. Department of Health and Human Services. Method(s): F344/N male and female F344/N rats (10/sex/group) received gavage doses of 0, 12, 25, 50, 100, or 200 mg/kg bromoform in corn oil 5 days/week for 13 weeks. The rats were observed twice per day and weighed weekly. Critical effect: hepatic lesions (hepatocellular vacuolization) End point or Point of Departure (POD): NOAEL = 25 mg/kg, duration-adjusted NOAEL = 18 mg/kg/day Uncertainty Factors: UF = 100 (10 each for intraspecies variability and interspecies extrapolation)

Tier 3 Source: MDEQ: Per DEQ-CCD, RRD adopted the IRIS value; however the RfD (1.8E-2

CHEMICAL UPDATE WORKSHEET Bromoform (75-25-2)

Source*/Reference Comments/Notes Part 201 Value Updated Value /Date /Issues mg/kg/day) differs from the IRIS in that two significant figures are presented.

Oral Cancer Slope Factor (CSF) 6.4E-3 7.9E-3 IRIS, 1991 (mg/kg-day)-1) Tier 1 Source: IRIS: Complete Basis: IRIS is a Tier 1 source. Critical Study: NTP (National Toxicology Program). 1988. Technical Report on the 2-year (corn oil) Toxicology and Carcinogenesis Studies of Tribromomethane (Bromoform) (CAS gavage No. 75-25-2) in F344 rats and B6C3F1 mice (gavage studies). NTP TR 350. carcinogenicity Method(s): F344/N rats and B6C3F1 mice (50/sex/group) were administered bioassay in rats & bromoform in corn oil by gavage 5 days/week for 2 years at 0, 100, or 200 mg/kg mice (NTP, 1988). (rats and female mice) or 0, 50, or 100 mg/kg (male mice) Neoplastic lesions 1) Dose response data: Tumor Type - Neoplastic lesions in the large intestine; in the large Test Species - F344/N rat, female; Route - gavage in corn oil intestine. 2) Extrapolation method: Linearized multistage procedure, extra risk Revised species Carcinogen Weight-of-Evidence (WOE) Class: B2, probable human carcinogen CSF details scaling factor of IRIS WOE Basis: inadequate human data and sufficient evidence of carcinogenicity (BWh/BWa) to the in animal species (increased incidence of tumors after oral administration in rats 0.25 power used and intraperitoneal administration in mice) for q* calculation. Source and Date: IRIS, Last revision date - 1/1/1991. EPA screening-level review in September 2002 identified one or more significant new studies Source: MDEQ/SWQD Tier 1 and 2 Sources: DEQ-CCD date: PPRTV: PPRTV (4/14/2005) refers to IRIS CSF. 1/10/2000 MRL: NA; MRLs are for non-cancer effects only.

Tier 3 Source: MDEQ: Per DEQ-CCD, CSF = 6.4E-3 (mg/kg/day)-1. RRD applied a revised species bodyweight scaling factor to calculate the CSF. Reference -- NA MDEQ, 2015 Concentration

CHEMICAL UPDATE WORKSHEET Bromoform (75-25-2)

Source*/Reference Comments/Notes Part 201 Value Updated Value /Date /Issues (RfC) or Initial Threshold Screening Level (ITSL) (µg/m³) Tier 1 and 2 Sources: IRIS: Per IRIS (1/01/1991), no value at this time. Complete PPRTV: Per PPRTV (4/14/2005), no value at this time. RfC/ITSL details NA MRL: Per ATSDR (July, 2013), no inhalation MRL at this time.

Tier 3 Source: MDEQ: Per DEQ-CCD, no value at this time. Inhalation Unit Risk Factor 1.1E-6 1.1E-6 IRIS, 1991 (IURF) ((µg/m3)-1) Tier 1 Source: IRIS: Complete Basis: IRIS is the only available information. IURF was derived using the oral NTP (1989) data. See RfD details below for additional information. Critical Study: NTP (National Toxicology Program). 1989. Toxicology and Carcinogenicity Studies of Tribromomethane and Bromoform in F344/N rats and B6C3F1 mice (gavage study). NTP-350. Research Triangle Park, NC. Method(s): Bromoform was administered by gavage to 1) F344/N rats (10/sex/dose) with 0, 12, 25, 50, 100, or 200 mg/kg, 2) B6C3F1 mice (10/sex/dose) IURF details NA with 0, 25, 50, 100, 200, or 400 mg/kg bromoform for 5 days/week for 13 weeks. Critical effect: increased clear cell foci of the liver in male rats End point or Point of Departure (POD): NOAEL = 25 mg/kg converted to 17.9 mg/kg/day (duration-adjusted) Uncertainty Factors: UF = 1,000 (10 each for intraspecies variability, interspecies extrapolation, and use of subchronic study) Source and Date: IRIS, Last revision date - 1/01/1991

Tier 1 and 2 Sources: PPRTV: PPRTV (4/14/2005) refers to IRIS IURF.

CHEMICAL UPDATE WORKSHEET Bromoform (75-25-2)

Source*/Reference Comments/Notes Part 201 Value Updated Value /Date /Issues MRL: NA; MRLs are for non-cancer effects only.

Tier 3 Source: MDEQ: Per DEQ-CCD, AQD adopted IRIS value for IURF. Mutagenic Mode of Action -- NO USEPA, 2015 (MMOA)? (Y/N) NA -- MMOA Details Not listed as a carcinogen with mutagenic MOA in the USEPA OSWER List. Developmental or No, the RfD is not based on a reproductive-developmental Reproductive No effect. MDEQ, 2014 Effector? (Y/N) Developmental or Reproductive NA NA Toxicity Details State Drinking 80 80 (total*) SDWA, 1976 Water Standard (SDWS) (ug/L) *The value is for total trihalomethanes. EPB-CCD Entry

SDWS details date: 11/2/2004 Source: MI Safe Drinking Water Act (SDWA) 1976 PA 399 Secondary SDWA, 1976 and Maximum -- NO Contaminant Level USEPA SMCL List (SMCL) (ug/L) SMCL details NA MI Safe Drinking Water Act (SDWA) 1976 PA 399 and USEPA SMCL List, 2015 Is there an aesthetic value for NO Not evaluated. NA drinking water? (Y/N) Aesthetic value NA NA NA (ug/L) Aesthetic Value NA NA details

CHEMICAL UPDATE WORKSHEET Bromoform (75-25-2)

Source*/Reference Comments/Notes Part 201 Value Updated Value /Date /Issues Phytotoxicity NO Not evaluated. NA Value? (Y/N) Phytotoxicity NA NA NA details Others

CHEMICAL UPDATE WORKSHEET Bromoform (75-25-2)

(C) Chemical-specific Absorption Factors Source/Reference/ Comments/Notes Part 201 Value Update Dates /Issues Gastrointestinal MDEQ, 2015/USEPA RAGS- absorption --- 1.0 efficiency value E, 2004 (ABSgi) ABSgi details RAGS E (USEPA, 2004) Default Value Skin absorption efficiency value --- 0.1 MDEQ, 2015 (AEd) AEd details Ingestion Absorption 1.0 MDEQ, 2015 Efficiency (AEi) AEi Details Relative Source Contribution for 0.2 MDEQ, 2015 Water (RSCW)

Relative Source Contribution for 1.0 MDEQ, 2015 Soil (RSCS)

Relative Source Contribution for 1.0 MDEQ, 2015 Air (RSCA)

Others

CHEMICAL UPDATE WORKSHEET Bromoform (75-25-2)

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

Updated GSI value (g/L) ID

Rule 57 Drinking Water Value (g/L) 52

Rule 57 Value Verification Date (g/L) Human Non-cancer Values- Drinking water source (HNV-drink) 470 1/1998

Human Non-Cancer Values- Non-drinking water sources (HNV-Non-drink) 8,100 1/1998

Wildlife Value (WV) NA NA

Human Cancer Values for Drinking Water Source (HCV-drink) 52 1/1998

Human Cancer values for non-drinking water source (HCV-Non-drink) 890 1/1998

Final Chronic Value (FCV) ID 12/1997

Aquatic maximum value (AMV) ID 12/1997

Final Acute Value (FAV) ID 12/1997 Sources: 1. MDEQ Surface Water Assessment Section Rule 57 website 2. MDEQ Rule 57 table

CHEMICAL UPDATE WORKSHEET Bromoform (75-25-2)

(E) Target Detection Limits (TDL) Value Source

Target Detection Limit – Soil (g/kg) 100 MDEQ, 2015

Target Detection Limit – Water (g/L) 1 MDEQ, 2015

Target Detection Limit – Air (ppbv) 2.30E+00 MDEQ, 2015

Target Detection Limit – Soil Gas (ppbv) 7.60E+01 MDEQ, 2015

CHEMICAL UPDATE WORKSHEET Bromoform (75-25-2)

CHEMICAL UPDATE WORKSHEET ABBREVIATIONS: W9 USEPA’s User Guide for Water9 Software, Version 2.0.0, 2001 CAS # - Chemical Abstract Service Number.

Section (A) Chemical-Physical Properties Reference Source(s): Basis/Comments: CRC Chemical Rubber Company Handbook of Chemistry EST estimated and Physics, 95th edition, 2014-2015 EXP experimental EMSOFT USEPA Exposure Model for Soil-Organic Fate and EXT extrapolated Transport (EMSOFT) (EPA, 2002) NA not available or not applicable EPA2001 USEPA (2001) Fact Sheet, Correcting the Henry’s NR not relevant Law Constant for Soil Temperature. Office of Solid Waste and Emergency Response, Washington, D.C. Section (B) Toxicity Values/Benchmarks EPA4 USEPA (2004) User’s Guide for Evaluating Sources/References: Subsurface Vapor Intrusion into Buildings. February ATSDR Agency for Toxic Substances and Disease Registry 22, 2004. CALEPA California Environmental Protection Agency EPI USEPA’s Estimation Programs Interface SUITE 4.1, CAL DTSC California Department of Toxic Substances Control Copyright 2000-2012 CAL OEHHA CAEPA Office of Environmental Health Hazard HSDB Hazardous Substances Data Bank Assessment MDEQ Michigan Department of Environmental Quality CCD MDEQ Chemical Criteria Database NPG National Institute for Occupational Safety and ECHA European Chemicals Agency (REACH) Health Pocket Guide to Chemical Hazards OECD HPV Organization for Economic Cooperation and PC National Center for Biotechnology Information’s Development HPV Database PubChem database HEAST USEPA’s Health Effects Assessment Summary Tables PP Syracuse Research Corporation’s PhysProp database IRIS USEPA’s Integrated Risk Information System SCDM USEPA’s Superfund Chemical Data Matrix MADEP Massachusetts Department of Environmental SSG USEPA’s Soil Screening Guidance: Technical Protection Background Document, Second Edition, 1996 MDEQ/DEQ Michigan Department of Environmental Quality USEPA/EPA United States environmental protection agency’s DEQ-CCD/AQD MDEQ Air Quality Division Risk Assessment Guidance for Superfund Volume I: DEQ-CCD/RRD MDEQ Remediation and Redevelopment Division Human Health Evaluation Manual (Part E, DEQ-CCD/WRD MDEQ Water Resources Division Supplemental Guidance for Dermal Risk MNDOH Minnesota Department of Health Assessment). July, 2004.

CHEMICAL UPDATE WORKSHEET Bromoform (75-25-2)

NJDEP New Jersey Department of Environmental RfC Reference concentration Protection RfD Reference dose NYDEC New York State Department of Environmental p-RfD Provisional RfD Conservation aRfD Acute RfD OPP/OPPT USEPA’s Office of Pesticide Programs UF Uncertainty factor PPRTV USEPA’s Provisional Peer Reviewed Toxicity Values WOE Weight of evidence RIVM The Netherlands National Institute of Public Health and the Environment Section (C) Chemical-specific Absorption Factors TCEQ Texas Commission on Environmental Quality MDEQ Michigan Department of Environmental Quality USEPA United States Environmental Protection Agency USEPA RAGS-E United States Environmental Protection Agency’s USEPA OSWER USEPA Office of Solid Waste and Emergency Risk Assessment Guidance for Superfund Volume I: Response Human Health Evaluation Manual (Part E, USEPA MCL USEPA Maximum Contaminant Level Supplemental Guidance for Dermal Risk WHO World Health Organization Assessment). July, 2004. WHO IPCS International Programme on Chemical Safety (IPCS/INCHEM) Section (D) Rule 57 Water Quality Values and GSI Criteria WHO IARC International Agency for Research on Cancers GSI Groundwater-surface water interface NA Not Available. NA A value is not available or not applicable. NR Not Relevant. ID Insufficient data to derive value NLS No literature search has been conducted 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