CHEMICAL UPDATE WORKSHEET
Chemical Name: Hexachlorobutadiene CAS #: 87-68-3 Revised By: RRD Toxicology Unit
Revision Date: August 18, 2015
(A) Chemical-Physical Properties Part 201 Value Updated Value Reference Source Comments
Molecular Weight (g/mol) 260.76 260.76 EPI EXP
Physical State at ambient temp Liquid Liquid MDEQ
Melting Point (˚C) 253 -21.00 EPI EXP
Boiling Point (˚C) 215 215.00 EPI EXP
Solubility (ug/L) 3230 3200 EPI EXP
Vapor Pressure (mmHg at 25˚C) 0.1748 2.20E-01 EPI EXP
HLC (atm-m³/mol at 25˚C) 8.15E-3 1.03E-02 EPI EXP
Log Kow (log P; octanol-water) 4.81 4.78 EPI EXP
Koc (organic carbon; L/Kg) 53500 845.2 EPI EST
Ionizing Koc (L/kg) NR NA NA
Diffusivity in Air (Di; cm2/s) 0.0561 2.67E-02 W9 EST
Diffusivity in Water (Dw; cm2/s) 6.16E-6 7.03E-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) NA 90 PC EXP
Lower Explosivity Level (LEL; unitless) NA NA NA NA
Critical Temperature (K) 7.38E+02 EPA2004 EXP
Enthalpy of Vaporization (cal/mol) 1.02E+04 EPA2004 EXP
Density (g/mL, g/cm3) 1.556 CRC EXP
EMSOFT Flux Residential 2 m (mg/day/cm2) 7.64E-06 2.56E-05 EMSOFT EST
EMSOFT Flux Residential 5 m (mg/day/cm2) 7.66E-06 5.37E-05 EMSOFT EST
EMSOFT Flux Nonresidential 2 m (mg/day/cm2) 9.15E-06 3.97E-05 EMSOFT EST
EMSOFT Flux Nonresidential 5 m (mg/day/cm2) 9.16E-06 7.92E-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) 2.0E-3 1.0E-3 PPRTV, 2007
RfD details
Rat chronic feeding study. NOAEL = 0.2 mg/kg; LOAEL = 2 mg/kg; Critical effect = kidney toxicity. UF = 100; (Kociba et al., 1977).
Tier 2 Source: PPRTV: Basis: PPRTV is a Tier 2 source and is a more current evaluation than MRL; no Tier 1 available. PPRTV RfD = 1.0E-3 mg/kg-day Critical Study: NTP. 1991. NTP Report on the Toxicity Studies of Hexachloro-1, 3-butadiene in B6C3F1 Mice (Feed Studies). U.S. Department of Health and Human Services, Research Triangle Park, NC. NIH Publication No. 91-3120. Yang, R.S., K.M. Abdo, M.R. Elwell, A.C. Levy and L.H Brennecke. (1989) Sub chronic toxicology studies of hexachloro-1, 3-butadiene (HCBD) in B6C3F1 mice by dietary incorporation. J. Environ. Pathol. Toxicol. Oncol. 9:323-332. Method(s): B6C3F1 mice (n=10/sex/dose) were administered hexachlorobutadiene in the diet at average daily doses of 0, 0.1, 0.4, 1.5, 4.9 or 16.8 mg/kg-day in males and 0, 0.2, 0.5, 1.8, 4.5 or 19.2 mg/kg-day in females for 13 weeks. Critical effect: Renal tubule regeneration. End point or Point of Departure (POD): The POD is set equal to the BMDL10 of 0.1 mg/kg-day. The quantal Benchmark Dose (BMD) models in the BMD software package (U.S. EPA, 2007; Version 1.3.2) were fit to the female mouse renal tubule regeneration data in Table 1 (NTP, 1991; Yang et al., 1989). The gamma, log-probit, Weibull and log-logistic give virtually the same fit with indistinguishable Akaike Information Criterion (AIC). The BMD and BMDL10 values were all the same at 0.2 and 0.1 mg/kg-day, respectively. The Weibull had the best fit in the region of the BMR (lowest absolute scaled residual at 0.2 mg/kg-day, although the differences among the models are minimal (see Appendix 1). The 1st-order multistage fit adequately (p = 0.37) but had a much higher AIC than the aforementioned model fits. Uncertainty Factors: = 100 (3 [i.e., 100.5] for interspecies extrapolation, 3 for database deficiencies, and 10 for interspecies variability). A sub chronic-to-
Complete
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Part 201 Value Updated Value Source/Reference/Date
Comments/Notes/Issues
chronic uncertainty factor was not included because a chronic 2-year rat study (Kociba et al., 1977) indicates that prolonged exposure does not result in toxicity at lower doses than for sub chronic exposure. Source: PPRTV, 07/13/2007 Tier 1 and 2 Sources: IRIS: The RfD was withdrawn on 05/01/1993 as a result of further review. An updated RfD was never provided. MRL (05/1994): Oral intermediate MRL of 0.0002 mg/kg/day Critical Study: NTP. 1991. National Toxicology Program. Toxicity studies of hexachloro-1, 3-butadiene in B6C3F1 mice (feed studies). Research Triangle Park, NC: U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health. NIH publication no. 91-3120. Critical effect: kidney damage in female mice. Tubular cell degeneration and regeneration in the renal cortex were found in treated animals. End Point or Point of Departure (POD): a LOAEL of 0.2 mg/kg/d was identified for kidney damage in female mice. Uncertainty Factors: = 1,000 (specific uncertainty factor contributions to the total were not specified). A chronic-duration study in animals revealed tubular hyperplasia in rats at dose levels of 2 mg/kg/day or greater (Kociba et al. 1977), but not at 0.2 mg/kg/day, the LOAEL for kidney effects from the intermediate-duration study in mice. Because the intermediate-duration MRL protects against chronic exposures, a chronic MRL has not been proposed. Final Toxicological Profile 05/1994. An addendum to the Tox Profile was published in December 2012 but no changes in the MRL were produced. Tier 3 Source: MDEQ-WRD, 04/07/1997 calculation date: RfD = 6.7E-5 mg/kg/d. Male and female B6C3F1 mice were fed 0, 1, 3, 10, 30, or 100 ppm hexachlorobutadiene for 13 weeks in studies conducted by Yang et al. (1988) and Yang (1991). A LOAEL of 0.2 mg/kg/d was found in female mice for renal toxicity (UF=3,000). No NOAEL
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Part 201 Value Updated Value Source/Reference/Date
Comments/Notes/Issues
for female mice was available in this study due to the incidence of renal tubular cell regeneration which occurred in at least one mouse in each treatment group.
Oral Cancer Slope Factor (CSF) (mg/kg-day)-1)
5.2E-2 7.8E-2 IRIS, 1991
CSF details
Renal tumors in male rats generated the highest potency value in a two-year cancer bioassay conducted by Kociba (1977). Rats were administered 0.2, 2, or 20 mg/kg/d in the feed for 22 months. Revised species scaling factor of (BWh/BWa) to the 0.25 power used for q* calculation. RD calculation date: 1/13/00.
Tier 1 Source: IRIS: Basis: IRIS is a Tier 1 source. IRIS cancer slope factor = 7.8E-2 per mg/kg-day Critical Study: Kociba, R.J., D.G. Keyes, G.C. Jersey, et al. (1977) Results of a two-year chronic toxicity study with hexachlorobutadiene in rats. Am. Ind. Hyg. Assoc. J. 38: 589-602. Method(s): Sprague-Dawley rats (n=39-40/sex/dose) were fed hexachlorobutadiene in diet at 0, 0.2, 2, or 20 mg/kg/d for up to 24 months. Critical effect: renal tubular adenomas and adenocarcinomas in male rats Carcinogen Weight-of-Evidence (WOE) Class: C; possible human carcinogen. IRIS WOE Basis: Observation of renal neoplasms in male and female rats in one study. Source: IRIS, 04/01/1991 Tier 2 Sources: PPRTV: Per PPRTV, The carcinogenicity assessment, which includes an oral slope factor and inhalation unit risk, is on IRIS (U.S. EPA, 1991). MRL: NA, MRLs are developed for non-cancer effects only. Tier 3 Source: MDEQ-RRD: Per DEQ-CCD, oral cancer slope factor = 0.052 per mg/kg-day (Kociba et al., 1977). 01/13/2000.
Complete
Reference Concentration (RfC) or Initial Threshold Screening Level (ITSL) (µg/m³)
NA NA MDEQ, 2015
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Part 201 Value Updated Value Source/Reference/Date
Comments/Notes/Issues
RfC/ITSL details
Tier 1 and 2 Sources: IRIS (05/01/1993): Per IRIS: not available at this time. PPRTV: Per PPRTV (7/13/2007), the available data are inadequate to support derivation of a provisional inhalation RfC for HCBD. Reduced body weight gain was observed in dams following inhalation exposure in the Saillenfait et al. (1989) rat developmental toxicity study (NOAEL of 2 ppm). However, this study included limited evaluation of non-developmental endpoints, no examination of the respiratory tract and no assessment of kidney toxicity, the critical effect for oral exposure. The only other inhalation study of appropriate duration to consider for RfC derivation is the Dow Chemical study briefly described by Torkelson and Rowe (1982). However, the existing description of this study provides insufficient information to assess the study, and attempts by the PPRTV authors to obtain more detailed information about the study were unsuccessful. The database for oral toxicity of HCBD is more extensive than that for inhalation toxicity (ATSDR, 1994). The kidney appears to be the most sensitive target of HCBD by oral exposure. However, due to overt signs of respiratory irritation and uncertainty regarding the relative sensitivity of the respiratory tract as compared to the kidney with long-term inhalation exposure, an RfC is not derived. MRL (05/1994): Inhalation MRLs have not been derived for any duration category due to the lack of sufficient data to identify a target organ and reliable NOAEL values. Tier 3 Source: MDEQ-AQC: No AQD ITSL entry in DEQ-CCD.
Complete
Inhalation Unit Risk Factor (IURF) ((µg/m3)-1)
2.2E-5
2.2E-5 IRIS, 1991
IURF details
Tier 1 Source: IRIS: Basis: IRIS is the only available value. IRIS IURF = 2.2E-5 per µg/m3. Per IRIS (4/1/1991), the IUR was calculated from the oral exposure data as noted in the oral cancer slope factor section. See IRIS oral CSF section for details.
Complete
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Part 201 Value Updated Value Source/Reference/Date
Comments/Notes/Issues
Tier 2 Sources: PPRTV: Per PPRTV, 07/13/2007, the carcinogenicity assessment, which includes an oral slope factor and inhalation unit risk, is on IRIS (U.S. EPA, 1991). MRL: NA, MRLs are developed for non-cancer effects only. Tier 3 Source: MDEQ: AQD uses the same value as IRIS. Calculation date: 02/27/1995.
Mutagenic Mode of Action (MMOA)? (Y/N)
-- No USEPA, 2015
MMOA Details --
Developmental or Reproductive Effector? (Y/N)
No
No
MDEQ, 2015
Developmental or Reproductive Toxicity Details
No, the RfD is not based on a reproductive-developmental effect.
State Drinking Water Standard (SDWS) (µg/L)
NA NO SDWA, 1976
SDWS details MI Safe Drinking Water Act (SDWA) 1976 PA 399
Secondary Maximum Contaminant Level (SMCL) (µg/L)
NA NO SDWA, 1976 and USEPA SMCL List
SMCL details MI Safe Drinking Water Act (SDWA) 1976 PA 399 and USEPA SMCL List, 2015
Is there an aesthetic value for drinking water? (Y/N)
No Not evaluated. NA
Aesthetic value NA NA
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Part 201 Value Updated Value Source/Reference/Date
Comments/Notes/Issues
details
Phytotoxicity Value? (Y/N) No Not evaluated. NA
Phytotoxicity details 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) 0.053
Updated GSI value (g/L) 0.053
Rule 57 Drinking Water Value (g/L) 0.093
Rule 57 Value
(g/L) Verification Date
Human Non-cancer Values- Drinking water source (HNV-drink) 0.093 4/1997
Human Non-Cancer Values- Non-drinking water sources (HNV-Non-drink) 0.098 4/1997
Wildlife Value (WV) 0.053 6/1999
Human Cancer Values for Drinking Water Source (HCV-drink) 0.33 4/1997
Human Cancer values for non-drinking water source (HCV-Non-drink) 0.35 4/1997
Final Chronic Value (FCV) 1 4/1999
Aquatic maximum value (AMV) 7 4/1999
Final Acute Value (FAV) 15 4/1999
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) 50 MDEQ, 2015
Target Detection Limit – Water (g/L) 0.05 MDEQ, 2015
Target Detection Limit – Air (ppbv) 1.10E-01 MDEQ, 2015
Target Detection Limit – Soil Gas (ppbv) 3.70E+00 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