Document Detail

Derivation of an Oral Reference Dose (RfD) for the Nonphthalate Alternative Plasticizer 1,2-Cyclohexane Dicarboxylic Acid, Di-Isononyl Ester (DINCH).
MedLine Citation:
PMID:  24627975     Owner:  NLM     Status:  In-Data-Review    
1,2-Cyclohexanedicarboxylic acid, 1,2-diisononylester (DINCH), a polyvinyl chloride plasticizer, has food, beverage, and medical device applications that may result in general population exposure. Although no apparent toxicity information in humans was identified, there is a substantial data set in lab animals to serve as the basis of hazard identification for DINCH. Target tissues associated with repeated dietary DINCH exposure in lab animals included liver, kidney, and thyroid and mammary glands. In contrast to some phthalate ester plasticizers, DINCH did not show evidence of hepatic peroxisomal proliferation, testicular toxicity, or liver tumors in rats. Liver and thyroid effects associated with DINCH exposure were attributed to compensatory thyroid stimulation secondary to prolonged metabolic enzyme induction. The toxicological significance of mammary fibroadenomas in female rats is unclear, given that this common benign and spontaneously occurring tumor type is unique to rats. The weight of evidence suggests DINCH is not genotoxic and the proposed mode of action (MOA) for thyroid gland lesions was considered to have a threshold. No adverse reproductive effects were seen in a two-generation study. An oral reference dose (RfD) of 0.7 mg/kg-d was derived from a human equivalent BMDL10 of 21 mg/kg-d for thyroid hypertrophy/hyperplasia seen in adult F1 rats also exposed in utero. The total uncertainty factor of 30x was comprised of intraspecies (10×) and database (3×) factors. An interspecies extrapolation factor was not applied since rodents are more sensitive than humans with respect to the proposed indirect MOA for thyroid gland lesions.
Virunya S Bhat; Jennifer L Durham; Gwendolyn L Ball; J Caroline English
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of toxicology and environmental health. Part B, Critical reviews     Volume:  17     ISSN:  1521-6950     ISO Abbreviation:  J Toxicol Environ Health B Crit Rev     Publication Date:  2014  
Date Detail:
Created Date:  2014-03-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9802627     Medline TA:  J Toxicol Environ Health B Crit Rev     Country:  England    
Other Details:
Languages:  eng     Pagination:  63-94     Citation Subset:  IM    
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