CHEMICAL UPDATE WORKSHEET Chemical Name: 1,4-Dichlorobenzene CAS #: 106-46-7 Revised By: RRD Toxicology Unit Revision Date: September 16, 2015 (A) Chemical-Physical Properties Part 201 Value Updated Value Reference Source Comments Molecular Weight (g/mol) 147 147.00 EPI EXP Physical State at ambient temp Solid Solid MDEQ Melting Point (˚C) --- 52.09 EPI EXP Boiling Point (˚C) 174 174.00 EPI EXP Solubility (ug/L) 73800 8.13E+04 EPI EXP Vapor Pressure (mmHg at 25˚C) 1.064 1.74E+00 EPI EXP HLC (atm-m³/mol at 25˚C) 2.43E-3 2.41E-03 EPI EXP Log Kow (log P; octanol-water) 3.42 3.44 EPI EXP Koc (organic carbon; L/Kg) 612 375.3 EPI EST Ionizing Koc (L/kg) NR NA NA Diffusivity in Air (Di; cm2/s) 0.069 5.50E-02 W9 EST Diffusivity in Water (Dw; cm2/s) 7.9E-6 8.6797E-06 W9 EST CHEMICAL UPDATE WORKSHEET 1,4-Dichlorobenzene (106-46-7) Part 201 Value Updated Value Reference Source Comments Soil Water Partition Coefficient NR NR NA NA (Kd; inorganics) Flash Point (˚C) 150 F 66 CRC EXP Lower Explosivity Level (LEL; 0.025 0.025 NPG EXP unit less) Critical Temperature (K) 6.85E+02 EPA2004 EXP Enthalpy of Vaporization 9.27E+03 EPA2004 EXP (cal/mol) 3 Density (g/mL, g/cm ) 1.2475 PC EXP EMSOFT Flux Residential 2 m 2.19E-05 2.57E-05 EMSOFT EST (mg/day/cm2) EMSOFT Flux Residential 5 m 3.77E-05 5.42E-05 EMSOFT EST (mg/day/cm2) EMSOFT Flux Nonresidential 2 m 2.99E-05 3.99E-05 EMSOFT EST (mg/day/cm2) EMSOFT Flux Nonresidential 5 m 4.77E-05 8.03E-05 EMSOFT EST (mg/day/cm2) 2 CHEMICAL UPDATE WORKSHEET 1,4-Dichlorobenzene (106-46-7) (B) Toxicity Values/Benchmarks Source*/Reference Comments/Notes Part 201 Value Updated Value /Date /Issues Reference Dose -- 7.0E-2 ATSDR, 2006 (RfD) (mg/kg/day) Tier 2 Source: Complete ATSDR: Basis: The IRIS RfD is based on a 2003 IRIS external draft document and newer studies. MDEQ (2011) RfD is based on an older study (Hollingsworth, 1956). ATSDR (7/2006), chronic oral MRL = 0.07 mg/kg-day. Critical Study(ies): 1) Naylor MW, Stout LD. 1996. One year study of p-dichlorobenzene administered orally via capsule to beagle dogs. Environmental Health Laboratory, Monsanto Company, St. Louis, MO. Study No. ML-94-210, March 25, 1996. MRID# 43988802. Unpublished. 2) USEPA. 1996b. Data Evaluation Record (DER) for p-dichlorobenzene – chronic oral toxicity in dogs (MRID# 439888-01 and -02) for Section 6 (a) (2) and reregistration need. U.S. Environmental Protection Agency, Office of Prevention, Pesticides and Toxic Substances. NA RfD details Method(s): Beagle dogs (5/sex/dose) were exposed to 0, 10, 50, or 75 mg/kg/day 1,4-DCB by capsule for 1 year. It is presumed that dosing was 5 days/week. The 75 mg/kg/day dose is a time-weighted average level reflecting dose decreases at the beginning of the study in response to unexpected severe toxicity. An initial high dose of 150 mg/kg/day was adjusted to 100 mg/kg/day for males during week 3, and a further decrease to 75 mg/kg/day was made for both sexes at the beginning of week 6. Both high-dose males and females were untreated during weeks 4 and 5 to allow for recovery. Critical effect: increased serum alkaline phosphatase; hepatic effects (increased liver weight, changes in liver enzymes, and histopathology) End point or Point of Departure (POD): BMDL1sd = 10 mg/kg-day; BMDL1sd ADJ = 7 mg/kg-day Uncertainty Factors: UF = 100 (10 each for intraspecies variability and interspecies extrapolation) 3 CHEMICAL UPDATE WORKSHEET 1,4-Dichlorobenzene (106-46-7) Source*/Reference Comments/Notes Part 201 Value Updated Value /Date /Issues Source and date: ATSDR, 7/2006 Tier 1 and 2 Sources: IRIS: Per IRIS (1/01/1994), no value at this time. IRIS external draft (11/03/2003) calculates an RfD = 2.4E-3 mg/kg. Details are shown below: Critical Study: Monsanto Company. (1996) M.W. Naylor and L.D. Stout. One Year Study of p-Dichlorobenzene Administered Orally Via Capsule to Beagle Dogs. MRID No. 439888-02. Available from USEPA. Write to FOI, EPA, Washington, DC 20460. Method(s): male and female beagle dogs were administered 1,4-DCB in gelatin capsules, 5 days/week, at initial dose levels of 0, 10, 50, or 150 mg/kg-day (adjusted doses; 0, 7, 36, 107 mg/kg-day) (Monsanto Company, 1996) for 1 year. The high dose was adjusted to 100 mg/kg-day (71 mg/kg-day) during the third week of exposure for males and further reduced to 75 mg/kg-day (54 mg/kg-day) for both sexes at the beginning of week 6. Both males and females at the highest dose level were untreated during the fourth and fifth weeks to allow for recovery, while the lower dose groups received 1,4-DCB continuously. Critical effect: increase in the absolute and relative liver weight End point or Point of Departure (POD): BMDL = 0.237 mg/kg-day Uncertainty Factors: UF = 100 (10 each for intraspecies variability and interspecies extrapolation) Source and date: IRIS, Last revision date - 1/01/1994; IRIS external review draft, 11/03/2003 EPA-OPP: No RfD available. No dietary exposure expected Per Memo: Ingredient: para-Dichlorobenzene; Title HED chapter of the reregistration eligibility decision document (RED). Revised version. April 1, 2008 (table 3.5); Reregistration eligibility decision (RED) for para-dichlorobenzene. Revised December 2008. PPRTV: No PPRTV record available at this time. 4 CHEMICAL UPDATE WORKSHEET 1,4-Dichlorobenzene (106-46-7) Source*/Reference Comments/Notes Part 201 Value Updated Value /Date /Issues Tier 3 source: MDEQ: Per DEQ-CCD, RRD has no value at this time. WRD derived an RfD = 4.5E-2 mg/kg-day: Critical Study: Hollingsworth, 1956 Method(s): Female rats dosed by gavage, 5 days/week for 27 weeks Critical effect: End point or Point of Departure (POD): NOAEL = 18.8 mg/kg Uncertainty Factors: UF = 300 Source and date: MDEQ-CCD/WRD, 12/29/2011 Oral Cancer Slope IRIS, 2003/MDEQ, Factor (CSF) 1.3E-2 1.3E-2 -1 2011 (mg/kg-day) ) Tier 1 Source: IRIS: Complete Basis: IRIS is a Tier 1 source. IRIS external review draft (11/03/2003) CSFHED = 1.3E- NTP (1987): 2- 2 per mg/kg-day. MDEQ/WRD (2011) derived a similar CSF value (see below). year gavage study IRIS: Per IRIS (1/01/1994), no value at this time; Per IRIS External Rreview Draft in male mice, (11/03/2003), CSFHED = 1.3E-2 per mg/kg-day. Details are shown below: critical effect = Critical Study: NTP (National Toxicology Program) (1987) Toxicology and hepatocellular Carcinogenesis Studies of 1,4-Dichlorobenzene (CAS No. 106-46-7) in F344/N Rats adenoma and and B6C3F1 Mice (Gavage Studies). U.S. Department of Health and Human adenocarcinoma Services. NTP TR 319. NIH Publ. No. 87-2575. CSF details combined. Method(s): F344 rats and B6C3F1 mice (50/sex/dose group); Female rats and both Revised species sexes of mice received 0, 300 and 600 mg/kg and male rats received 0, 150 and scaling factor of 300 mg/kg-day of 1,4-DCB in corn oil gavage for 2 years. (BWh/BWa) to the 1) Dose response data: Tumor Type - hepatocellular adenomas or 0.25 power used carcinomas; Test Species - male mice; Route – oral (gavage) for q* calculation. 2) Extrapolation method: Linearized multistage extrapolation RD calculation Carcinogen Weight-of-Evidence (WOE) Class: likely to be carcinogenic in humans date: 1/12/2000 IRIS WOE Basis: increased tumor incidences in male rat kidneys and in the livers of male and female mice following oral exposure. The kidney tumors in rats are not relevant to humans because the mechanism is specific to male rats. The mechanistic bases of the mouse liver tumors are assessed to be relevant to 5 CHEMICAL UPDATE WORKSHEET 1,4-Dichlorobenzene (106-46-7) Source*/Reference Comments/Notes Part 201 Value Updated Value /Date /Issues humans. Source and Date: IRIS, last revision date - 1/01/1994 and IRIS External Review Draft, 11/03/2003 EPA-OPP (2013): Not Likely to be Carcinogenic to Humans below doses that do not perturb normal liver homeostasis. Based on the IRIS evaluation draft document of May 2006, the slope factor linear approach was suggested. Source and Date: USEPA-OPP Per Memo: Ingredient: para-Dichlorobenzene; Title HED chapter of the reregistration eligibility decision document (RED). Revised version. April 1, 2008 (table 3.5); Reregistation eligibility decision (RED) for para-dichlorobenzene. Revised December 2008 Tier 2 Sources: PPRTV: No PPRTV record available at this time. MRL: NA; MRLs are for non-cancer effects only. MDEQ: Per DEQ-CCD/RRD, RfD = 1.3E-2. See Part 201 Value CSF details. WRD (2011) calculated a CSF = 0.0129 (mg/kg-day)-1 based on lliver carcinomas/adenomas in male mice following treatment by gavage, 5 days/week for 103 weeks (NTP, 1987): Critical Study: NTP (National Toxicology Program) (1987) Toxicology and Carcinogenesis Studies of 1,4-Dichlorobenzene (CAS No. 106-46-7) in F344/N Rats and B6C3F1 Mice (Gavage Studies). U.S. Department of Health and Human Services. NTP TR 319. NIH Publ. No. 87-2575. Method(s): F344 rats and B6C3F1 mice (50/sex/dose group); Female rats and both sexes of mice received 0, 300 and 600 mg/kg and male rats received 0, 150 and 300 mg/kg-day of 1,4-DCB in corn oil gavage for 2 years.