Regulatory Toxicology and Pharmacology 35, 44–55 (2002) doi:10.1006/rtph.2001.1518, available online at http://www.idealibrary.com on Evaluation of the Carcinogenicity of 1,1-Dichloroethylene (Vinylidene Chloride) 1 Stephen M. Roberts, ∗ Kristen E. Jordan, ∗ D. Alan Warren,† Janice K. Britt,† and Robert C. James† , ∗ ∗ Center for Environmental & Human Toxicology, University of Florida, Gainesville, Florida; and †TERRA, Inc., Tallahassee, Florida Received March 8, 2001 The U.S. Environmental Protection Agency has clas- sified 1,1-dichloroethylene (vinylidene chloride; VDC) as a “C” carcinogen and has developed an inhalation unit risk value and an oral cancer slope factor for this chemical. The development and use of these cancer potency estimates for risk assessment purposes are questionable. The inhalation unit risk value is based on increased kidney adenocarcinomas in Swiss mice from one study. This type of cancer was not increased in female mice or in rats or hamsters in the same study nor in male mice of a similar strain in another study with higher VDC exposures. The VDC oral cancer slope factor is based on a non-statistically significant increase in adrenal pheochromocytomas in male rats following oral exposure in a standard National Toxi- cology Program chronic bioassay. Both human and an- imal literature relevant to VDC carcinogenicity was reviewed according to the USEPA draft Guidelines for Carcinogen Risk Assessment with the objective of determining the weight-of-evidence for VDC car- cinogenicity. We conclude that information currently available for VDC is most appropriately character- ized in a weight-of-evidence narrative by the descrip- tor “inadequate for an assessment of human carcino- genic potential.” For chemicals with this descriptor, dose–response assessment is not indicated. Under this guidance, quantitative estimates of cancer risks as- sociated with VDC exposure are inappropriate until additional, more definitive evidence for human car- cinogenicity becomes available. C  2002 Elsevier Science (USA) Key Words: vinylidene chloride; 1,1-dichloroethy- lene; 1,1-dichloroethene; carcinogenicity; risk assess- ment. INTRODUCTION 1,1-Dichloroethylene (CAS No. 75-35-4), commonly known as vinylidene chloride (VDC), is a volatile liquid 1 This analysis was initiated at the request of Walsh Environmental Scientists and Engineers, Inc. The analysis was conducted indepen- dently and without compensation, and the opinions expressed herein are solely those of the authors. that has been used as a chemical intermediate in the production of 1,1,1-trichloroethane and as a monomer in commercial resins and packaging materials. VDC is also an environmental degradation product of sev- eral chlorinated solvents (e.g., trichloroethylene, tetra- chloroethylene, and 1,1-dichloroethane) and can be found at sites contaminated with these solvents (Cole- man et al., 1977; Fishbein, 1979; Wallace et al., 1986). VDC is a central nervous system depressant in humans when inhaled (USEPA, 1979) and repeated exposure to low concentrations of VDC may cause liver and renal dysfunction in humans (Torkelson and Rowe, 1981). In laboratory animals, liver, kidney, and lung are the ma- jor target organs for VDC toxicity following acute and chronic inhalation exposure (Gage, 1970; Short et al., 1977; Reitz et al., 1980; Plummer et al., 1990). The potential carcinogenicity of VDC has been evalu- ated in several laboratory animal species by a number of routes of exposure (Maltoni, et al., 1977, 1982, 1985; Viola and Caputo, 1977; Lee et al., 1978; Van Duuren et al., 1979; Hong et al., 1981; NTP, 1982; Quast et al., 1983). Significant increases in some tumor types were observed in a few of these studies, but these were not confirmed in other studies of VDC exposure using the same species. Noting weaknesses in many of these studies, the USEPA considered the weight-of-evidence for VDC consistent with classification in category C—a possible human carcinogen. An inhalation unit risk fac- tor for VDC (5 × 10 -5 per μg/m 3 ) was developed using the linearized multistage (LMS) procedure applied to data showing a significant increase in kidney adeno- carcinomas in male Swiss mice exposed to VDC by inhalation for 12 months (data from Maltoni et al., 1977, 1985). An oral cancer slope factor for VDC (0.6 per (mg/kg)/day) was derived from data on the incidence of adrenal pheochromocytomas in male F344 rats treated with VDC by gavage for 24 months (NTP, 1982). This oral cancer slope factor is unusual in that it is based on tumor incidences that were not significantly increased above controls. The USEPA has justified their derivation of a slope factor under these circumstances by stating that the oral cancer slope factor for these tumors is within a factor of 2 of the oral cancer slope 44 0273-2300/02 $35.00 C  2002 Elsevier Science (USA) All rights reserved.