The sub-chronic oral toxicity of dearomatized hydrocarbon solvents in Sprague-Dawley rats. 2014

David Adenuga, and Juan-Carlos Carrillo, and Richard H Mckee
ExxonMobil Biomedical Sciences, Inc., 1545 Route 22 E., Annandale, NJ 08801, USA. Electronic address: moyinoluwa.d.adenuga@exxonmobil.com.

Dearomatized hydrocarbon solvents in the C9-C14 aliphatic carbon number range were developed as alternatives to traditional solvents such as mineral spirits, but with lower aromatic content. Previous subchronic toxicity studies (both published and unpublished) have shown minimal to no systemic effects with exposure to dearomatized solvents, with the exception of rat-specific renal effects that have no relevance to humans. In this study, Sprague-Dawley rats were exposed to 0, 500, 2500 and 5000mg/kg/day of a C10-C13 dearomatized solvent for 90days by oral gavage. Liver enlargement and centrilobular hypertrophy were observed in all treated groups but were considered adaptive consequences of hydrocarbon-induced microsomal enzyme induction. Clinical chemistry data showed elevations of alanine aminotransferase (ALT), gamma glutamyltransferase (GGT) and total bilirubin in mid (ALT alone) and high dose groups, suggesting potential hepatobiliary effects with high dose exposure. Increased absolute kidney weight changes were restricted to male rats and associated with renal lesions indicative of alpha-2u globulin-mediated nephropathy. One limitation of the NOAEL/LOAEL approach in selecting points of departure for exposure limits is its dependence on dose selection/study design. Hence, a more robust approach that incorporates all data points on the dose-response curve, such as bench mark modeling, is preferred. Overall, benchmark dose analysis estimated a BMDL of 1857mg/kg/day based on increased serum ALT. This value is consistent with studies of similar hydrocarbon substances showing a lack of systemic effects at doses up to 1000mg/kg/day in the same rat strain.

UI MeSH Term Description Entries
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D001835 Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms. Body Weights,Weight, Body,Weights, Body
D002780 Cholestasis, Intrahepatic Impairment of bile flow due to injury to the HEPATOCYTES; BILE CANALICULI; or the intrahepatic bile ducts (BILE DUCTS, INTRAHEPATIC). Bile Duct Obstruction, Intrahepatic,Biliary Stasis, Intrahepatic,Intrahepatic Cholestasis,Biliary Stases, Intrahepatic,Cholestases, Intrahepatic,Intrahepatic Biliary Stases,Intrahepatic Biliary Stasis,Intrahepatic Cholestases
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005260 Female Females
D005723 gamma-Glutamyltransferase An enzyme, sometimes called GGT, with a key role in the synthesis and degradation of GLUTATHIONE; (GSH, a tripeptide that protects cells from many toxins). It catalyzes the transfer of the gamma-glutamyl moiety to an acceptor amino acid. GGTP,Glutamyl Transpeptidase,gammaglutamyltransferase,gamma-Glutamyl Transpeptidase,Transpeptidase, Glutamyl,Transpeptidase, gamma-Glutamyl,gamma Glutamyl Transpeptidase,gamma Glutamyltransferase
D006838 Hydrocarbons Organic compounds that primarily contain carbon and hydrogen atoms with the carbon atoms forming a linear or circular structure. Hydrocarbon,Saturated Hydrocarbons,Unsaturated Hydrocarbons,Hydrocarbons, Saturated,Hydrocarbons, Unsaturated
D000284 Administration, Oral The giving of drugs, chemicals, or other substances by mouth. Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations

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