Derivation of an oral reference dose (RfD) for di 2-ethylhexyl cyclohexan-1,4-dicarboxylate (DEHCH), an alternative...

Di 2-ethylhexyl cyclohexane-1,4-dicarboxylate (DEHCH, CAS 84731-70-4) is an ester of polycarboxylic acid assessed in a variety of mammalian toxicity assays as a substitute for phthalate ester-type plasticizers. An OECD 422 combined systemic toxicity study with a reproductive/developmental toxicity screening test in SD rats found minimal effects on the liver, spleen, and thyroid and no indication that DEHCH is a developmental or reproductive toxicant. In a 90-day feeding study in SD rats, no toxicologically relevant effects were noted. Low genotoxic potential of DEHCH is indicated by the lack of mutagenicity or clastogenicity in vitro. No studies assessing mode of action were identified. Where data gaps exist for DEHCH, a read-across approach was used to assess other toxicological endpoints of interest. Di-ethylhexyl terephthalate (DEHT, CAS 6422-86-2) and 1,2-cyclohexane dicarboxylic acid, diisononyl ester (DINCH, CAS 474919-59-0) have higher tiered studies to supplant the data lacking for health-based standard setting. DEHT and DINCH were chosen as the source substances due to similar physical/chemical properties and thus anticipated metabolism and toxicological characteristics. An oral reference dose (RfD) for DEHCH was calculated using the human equivalent NOAEL from the OECD 422 study. A total uncertainty factor of 100 was comprised of interspecies (3x), intraspecies (10x), subchronic to chronic (1x), LOAEL to NOAEL uncertainty (1x) and database uncertainty (3x) factors, resulting in an RfD of 0.3 mg/kg-day.