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Toxicol Lett. 2018 May 15;288:99-110. doi: 10.1016/j.toxlet.2018.02.008. Epub 2018 Feb 21.

Hexamoll® DINCH: Lack of in vivo evidence for obesogenic properties.

Author information

1
BASF SE, 67056 Ludwigshafen, Germany. Electronic address: angelika.langsch@basf.com.
2
BASF Corporation, Florham Park, NJ 07932, USA.
3
BASF SE, 67056 Ludwigshafen, Germany.
4
Metanomics GmbH, Berlin, Germany.

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 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.

KEYWORDS:

2-generation study; DEHP; Hexamoll(®) DINCH; Metabolome; Obesogen; Toxicokinetics

PMID:
29474903
DOI:
10.1016/j.toxlet.2018.02.008
[Indexed for MEDLINE]

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