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The potential of two trimellitate esters -  tris (2-ethylhexyl) trimellitate (TOTM) containing C8 branched alcohol side chains and 1,2,4-benzenetricarboxylic acid, decyl octyl ester containing linear C8 to C10 alcohol side chains - to induce testicular mal-development(TMD) has been studied in the rat and compared with the positive controls, di- (2-ethylhexyl) phthalate (DEHP) and its active metabolite, mono-(2-ethylhexyl) phthalate (MEHP). The effects of these trimellitates on the expression of genes in pathways involved in steroidogenesis and testes development previously shown to be involved in the induction of TMD by certain phthalate esters were studied using transcriptional profiling techniques on RNA extracted from the testes of rats exposed in utero to either the trimellitate ester or the positive controls. 

Additional information

Rats were exposed to two trimellitate esters - either tris (2-ethylhexyl) trimellitate (TOTM) containing C8 branched alcohol side chains or 1,2,4-benzenetricarboxylic acid, decyl octyl ester containing linear C8 to C10 alcohol side chains - in utero by the administration of daily oral gavage doses to pregnant dams between gestational day 12 and 19. The foetal testes were obtained by micro-dissection and prepared to facilitate the isolation of RNA, which was subsequently analysed using whole rat genome microarrays. The study was focussed on assessment of effects in pathways relevant to rat testicular mal-development (TMD). Effects were compared with those of diethylhexyl phthalate (DEHP) and mono-(2-ethylhexyl) phthalate (MEHP), an active metabolite of DEHP, both of which were used as a positive controls.

MEHP & DEHP (500 mg/Kg) caused a repression of genes in TMD pathways involved in cholesterol synthesis and transport (HMGCS, HMGCR, STAR, SCARB1, FDFT1, FDPS), Steroidogenesis (Cyp11a, HSD3B1, SC4MOL) and testes development (INSL3, INHA)

The trimellitate esters did not cause significant repression of genes in TMD pathway.

It was concluded that it is highly unlikely that the trimellitate esters will cause testicular mal-development in the rat under these treatment conditions.