Hexamoll® DINCH: Lack of in vivo evidence for obesogenic properties. (15th May 2018)

• Record Type: Journal Article
• Authors: Langsch, Angelika; David, Raymond M.; Schneider, Steffen; Sperber, Saskia; Haake, Volker; Kamp, Hennicke; Leibold, Edgar; Ravenzwaay, Bennard van; Otter, Rainer
• Is Part Of: Toxicology letters. Volume 288(2018)
• Page Start: 99
• Page End: 110
• Publication Date: 2018-05-15
• Subjects: ALP alkaline phosphatase -- ALT alanine aminotransferase -- AST aspartate aminotransferase -- BMI body mass index -- BROD Benzoxyresorufin-O-debenzylase -- CHDA cyclohexane 1, 2-dicarboxylic acid -- CYP Cytochrome P -- DEHP di-(2-ethylhexyl) phthalate -- EROD Ethoxyresorufin-O-deethylase -- GGT gamma glutamyl transferase -- HOBI-GT 4-Hydroxybiphenyl-glucuronyltransferase -- MEHP mono-(2-ethylhexyl) phthalate -- MUF-GT 4-Methylumbelliferone-glucuronyltransferase -- OPLS-DA orthogonal projection to latent structures discriminant analysis -- PPAR peroxisome proliferator-activated receptor -- PROD Pentoxyresorufin-O-depentylase -- SVF stromal vascular fraction; Hexamoll® DINCH -- DEHP -- Obesogen -- Toxicokinetics -- 2-generation study -- Metabolome; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2018.02.008
• Languages: English
• ISSNs: 0378-4274

Abstract

Highlights: In vivo data do not show any evidence of Hexamoll ® DINCH having obesogenic properties. No effects on body weight, total cholesterol values or lipid accumulation were observed. Toxicokinetics with radiolabeled Hexamoll ® DINCH do not indicate a potential for accumulation. Metabolomic profiles of Hexamoll ® DINCH and DEHP differ substantially. Abstract: Hexamoll ® DINCH is an important alternative to phthalate plasticizers. Although regulatory reviews have not identified any potential hazards even in sensitive populations, an in vitro study by Campioli et al. (2015) suggested Hexamoll ® DINCH might alter fat storage in adipocytes resulting in obesity. To evaluate this hypothesis, data from studies with Hexamoll ® DINCH were reviewed for evidence of deposition in fat, changes in body weight, or changes in serum chemistry reflecting altered metabolic status. Body weights of F1 and F2 pups in a two-generation study did not differ from controls even at 1000 mg Hexamoll ® DINCH/kg body weight. Mean relative liver weights from the 1000 and 300 mg/kg bw groups were increased, but without histopathologic changes. Triglyceride and cholesterol levels in serum were not affected. In addition, subchronic and chronic studies in rats did not give evidence of an obesogenic effect. Radioactivity from 20 or 1000 mg/kg bw 14 C-labelled Hexamoll ® DINCH dosed orally remained 2–3 times longer in adipose tissue than in well-perfused tissues; however, levels were 20–500% below other tissues at 1 and 8 h post dosing. Radioactivity concentrations in organs and tissues excluding the GI tract declined rapidly and continuously, and decreased in parallel to the concentration in plasma during the following 20 h. Both, initial and terminal half-lives of radioactivity concentration do not indicate a potential for accumulation. Furthermore, a metabolomic comparison of Hexamoll ® DINCH with DEHP and other phthalates shows complete separation of the metabolomic profile of these two chemical classes, meaning that their effects on the body and the body's reaction to the substance are different. Hence, comprehensive in vivo data do not show any evidence of Hexamoll ® DINCH altering fat metabolism or having obesogenic properties.