No abstract

The effects of multiple doses of desbromoleptophos, fenitrothion, and pure fenthion on brain acetylcholinesterase (AChE), brain neurotoxic esterase (NTE), and walking were investigated in immature chicks, below the age of sensitivity to organophosphorus ester-induced delayed neurotoxicity (OPIDN). Ten milligrams per kilogram per day of delayed neurotoxicant desbromoleptophos (DBL), 15 mg/kg.d of the non-neurotoxicant fenitrothion (FTR), and 3 mg/kg.d of the suspected neurotoxicant fenthion (FEN) were given orally for 7 d to 3-d-old chicks. Behavioral testing was performed for treated and control chicks on various days after treatment. Brain NTE and AChE assays were carried out for treated and control chicks on each day of behavioral testing. DBL altered gait and inhibited both NTE and AChE; FEN altered gait and inhibited AChE but not NTE; and FTR did not affect gait, while inhibiting AChE but not NTE. NTE and AChE inhibition were 70% and 55%, respectively, 24 h after the last treatment, for the chicks treated with DBL. NTE returned to normal levels by around d 25 and AChE by 20 d after the last treatment. FTR caused more than 50% AChE inhibition but no NTE inhibition, 24 h after last treatment. NTE inhibition for the FEN-treated chicks never exceeded 11% during the whole period of the experiment, whereas 54% inhibition of AChE was seen 1 d after last treatment. DBL and FEN significantly altered the gait of treated chicks, but the non-OPIDN-inducing FTR did not. This study confirms that alterations in the gait of young chicks are not direct consequences of either NTE or AChE inhibition, and that fenthion-induced functional deficits can be distinguished from classical OPIDN.

Eight pairs of O-methyl and O-ethyl O-(substituted-phenyl) phenylphosphonothionates were evaluated with respect to their delayed neurotoxic activity in hens. O-methyl compounds were in all cases more active than their O-ethyl analogs. The neurotoxic potential of the O-methyl phenylphosphonothionates was 2,5-diCl greater than 4-NO2 greater than 2,4,5-triCl and 2,4,6-triCl greater than 2,4-diCl greater than 2,5-diCl-4-Br greater than 4-CN, when single oral doses were given. Both EPN-ethyl and leptophos-methyl were more neurotoxic in multiple dermal than multiple oral dosing regimens. LD50s for mice and flies were established.

It was postulated that sex‐linked genes affecting embryonic sensitivity to cortisone‐induced cleft palate and cortisone‐induced resorption might differ between inbred mouse strains showing pronounced reciprocal effects. The three strains tested were the A/J (A), C57BL/6J (B), and C3H/HeJ (C), whose sensitivities to cortisone‐induced cleft palate had been shown to be: A > C > B. The sensitivity of reciprocal A × B and B × C hybrid embryos was matroclinous; of reciprocal A × C embryos, patroclinous. Backcrosses of reciprocal F1 hybrid males to inbred females were used to test the hypothesis of sex‐linkage with respect to the incidence of cortisone‐induced cleft palate, cortisone‐induced resorption, and the overall level of cortisone‐induced fetal damage. The results were consistent with the hypothesis that sex‐linked genes affecting embryonic sensitivity to cortisone‐induced cleft palate, but not to cortisone‐induced resorption, differ in the three strains.

The teratogenicity of the diphenyl ether herbicide bifenox [2,4-dichlorophenyl 3'-carboxymethyl-4'-nitrophenyl ether] was compared to that of nitrofen [2,4-dichlorophenyl 4'-nitrophenyl ether] in rats and in mice. Neither compound increased prenatal mortality in mice. Because nitrofen causes both malformations that are compatible with survival to weaning and a high incidence of perinatal (but not of fetal) mortality, emphasis was placed on postnatal parameters of bifenox toxicity. In rats, bifenox caused a low incidence of "bloody tears", but it did not decrease survival to term or to weaning in rats or mice, and did not reduce Harderian gland weight in mice. Because the weight of the Harderian glands is a more objective measure of their status than is the presence of an eye discharge, it is concluded that bifenox is not teratogenic at the levels administered. Nitrofen decreased litter size, pup weight, and Harderian gland weight in mice.