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4333704 
Journal Article 
Hexamoll® DINCH: Lack of in vivo evidence for obesogenic properties 
Langsch, A; David, RM; Schneider, S; Sperber, S; Haake, V; Kamp, H; Leibold, E; Ravenzwaay, BV; Otter, R 
2018 
Toxicology Letters
ISSN: 0378-4274
EISSN: 1879-3169 
Elsevier Ireland Ltd 
CLARE 
288 
99-110 
English 
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 14C-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. 
Hexamoll® DINCH; DEHP; Obesogen; Toxicokinetics; 2-generation study; Metabolome 
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     Source - August 2018 Update
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