The effect of trichlorfon and other organophosphates on prenatal brain development in the guinea pig

Abstract

The organophosphates trichlorfon, dichlorvos, dimethoate, soman, triortho-cresyl phosphate (TOCP), and the diethoxy-analogue of trichlorfon (O,O-diethyl 2,2,2-trichloro-1-hydroxyethylphosphonate, ethyl-trichlorfon), were administered to guinea pigs between day 42 and 46 of gestation. When the offsprings were examined at birth, there was a severe reduction in brain weight in the case of trichlorfon and dichlorvos, but not after treatment with the other organophosphates. The reduction in weight was most pronounced for cerebellum, medulla oblongata, thalamus/hypothalamus and quadrigemina. The effect was less marked for cerebral cortex and hippocampus. Since soman, a potent anticholinesterase, and TOCP, an inhibitor of neuropathy target esterase, did not show any effects, this excludes that the brain hypoplasia can be caused by inhibition of these two enzymes. Further, the lack of effect with ethyl-trichlorfon has shed some light on the part of the trichlorfon molecule which could be involved in the formation of the hypoplasia. It is suggested that alkylation of DNA may be involved in the development of the lesion. The possible consequences for a teratogenic effect of trichlorfon and dichlorvos on humans are discussed.

Impaired Mitochondrial Functions in Organophosphate Induced Delayed Neuropathy in Rats

“…Mitochondrial GSH plays a key role in the protection against the oxidative damage to mitochondrial lipids and proteins. In addition, reduction in GSH levels can also be attributed to alkylation of -SH group of GSH (Mehl et al 1994). The sensitivity of mitochondrial complexes also appears to be related to GSH availability.…”

Prenatal exposure of guinea pigs to the organophosphorus pesticide chlorpyrifos disrupts the structural and functional integrity of the brain

“…In humans, gross brain volumetric changes measurable by MR anatomical scans have been observed as a result of prenatal exposure to sub-acute doses of CPF (Rauh et al 2012). Earlier histological studies on prenatal exposure of guinea pigs to the related OP compound trichlorfon revealed a severe reduction in brain weight and hypoplasia of the cerebellar cortex in the affected animals(Mehl et al 1994, 2007). The prenatal period examined in the present study is a peak time for brain growth in guinea pigs, particularly in the frontal and striatal areas (Dobbing and Sands 1970; Kalaria and Prince 1988).…”

Pesticides as a source of developmental disabilities

“…Michalek et al [1990] did not perform any behavioral testing nor did they report observing overt cholinergic signs. Generally, the publications dealing with developmental OP toxicity tend to administer relatively high doses, or fail to measure AChE levels, or rely on crude behavioral end points [e.g., Mehl et al, 1994;Muto et al, 1992]. …”