5-Isobenzofurancarboxylic acid, 1,3-dihydro-1,3-dioxo-, reaction products with 1-nonanol

Toxicity to birds

Description of key information

In accordance with REACH Regulation 1907/2006, Annex X, Column 2, studies of the effects on birds need only be considered taking into account findings from the dataset on mammalian toxicity.
Mammalian toxicity data are considered sufficient to adequately characterise the substance with no effects levels greatly in excess of those that may potentially occur in the environment.

Additional information

In accordance with REACH Regulation 1907/2006, Annex X, Column 2, studies of the effects on birds need only be considered taking into account findings from the dataset on mammalian toxicity.

Sub-chronic repeated dose studies of 90 -days duration on two structural analogues of the registered substance resulted in minor effects in the liver at a dose level of 1000 mg/kg/day with a NOAEL of 500 mg/kg/day. A screening study of reproductive toxicity on one structural analogue of the registered substance revealed reduced spermatocytes and spermatids on histopathological examination of the testes of males given the substance at doses of 300 or 1000 mg/kg/day. Treatment had no effect on the appearance, condition or behaviour, body weight, food consumption, necropsy findings, weights of the testes, epididymis or ovaries, or histopathology of the ovaries. With the exception of the effects in males, treatment at dosages of 100, 300 or 1000 mg/kg/day had no effect on reproductive ability, organ weight or histopathology of the ovary, delivery or maternal behaviour of the dams. The testicular effects described in this screening study were not noted in a subchronic study on the substance despite the exposure period being significantly greater than that of the screening study. It is thought that in this class of substance, by association with the phthalate esters, the principle reproductive toxicity potential may be towards the developing male testes. This aspect of the toxicology of the substance has been studied adequately using RNA transcriptional profiling in which rats were exposed in-utero by administration of the substance by daily oral 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 focused on assessment of effects in pathways relevant to rat testicular mal-development (TMD). The effects of the two structural analogues investigated 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 and DEHP 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 two trimellitate esters did not cause significant repression of genes in TMD pathway.

These data are considered sufficient to adequately characterise the substance with no effects levels greatly in excess of those that may potentially occur in the environment.