Thomas B. Gaines

Acute toxicity of pesticides

Abstract LD50 values have been determined for 98 pesticides and 2 metabolites of DDT administered in a single dose by the oral or dermal route to Sherman strain adult rats. Most compounds tested by the oral route were more toxic to female than to male rats, but 9 of 85 compounds (aldrin, chlordane, heptachlor, Abate, Imidan, methyl parathion, ronnel, schradan, and metepa) tested in both sexes were markedly more toxic in male rats. Although the pesticides were generally more toxic by the oral than by the dermal route, 5 compounds (fenitrothion, Merphos, mevinphos, Isolan, and Omite) were more toxic by the dermal route. LD50 values for rats treated by the dermal route with parathion or dichlorvos and restrained so as to prevent the possibility of oral or respiratory exposure were not significantly different from those values in rats treated according to the procedure used routinely in this laboratory. In screening tests for the production of paralytic effect in chicken hens 3 of 9 carbamate and 22 of 30 organic phosphorus pesticides tested caused paralysis. The onset of paralysis was delayed at least 3 days in chickens treated with Dursban and Merphos and at least 14 days in chickens treated with DEF. Chickens treated with the other 22 pesticides that produced paralysis showed this effect within 24 hours.

Hexachlorophene Effects on the Rat Brain

Hexachlorophene was fed io female adult Sherman strain rats at 500 ppm (25 mg/kg/day) for 14 and 10 weeks in two consecutive studies. After two weeks on the diet containing hexachlorophene, the rats developed leg weakness which progressed to paralysis in three to five weeks. After ten weeks on these diets in the second study, hexachlorophene was discontinued; the rats regained almost complete recovery of leg function within six weeks. The brains of the rats that had ingested hexachlorophene weighed significantly more than those of controls and returned to normal in six weeks. The lesions produced by hexachlorophene in the rat brains represented cerebral edema limited to the white matter, which resembles diffuse spongy degeneration of the white matter of the brain described in infants.

Poisoning by DDT: Relation between Clinical Signs and Concentration in Rat Brain

The severity of signs of poisoning in rats after a single dose of DDT is directly proportional to the concentration of the compound in their brains. The concentrations associated with death after one large dose are about the same as those after many smaller doses.

Effect of Organic Phosphorus Compounds and Alkylating Agents on the Rat Fetus

The effects of parathion, dichlorvos, diazinon, malathion, apholate, and tepa on the rat fetus were studied when the material was given intraperitoneally. At levels producing toxic symptoms in the dams, parathion, dichlorvos, diazinon, apholate, and tepa were found to affect the fetus either by causing malformations, resorptions, or reducing the weight of the fetus and placenta. Malathion at toxic dosage levels neither affected the weight of the fetus nor produced malformations. At dosage levels which were tolerated by the dams, parathion, diazinon, and tepa caused a great number of resorptions. The incidence of resorptions was not higher than that of the controls in rats that had been given dichlorvos, malathion, or apholate.

2,4-Dichlorophenyl-p-Nitrophenyl Ether (TOK)

In a two-generation reproduction study, rats were fed dietary levels of 0, 20, 100, and 500 ppm of 2,4 dichlorophenyl-p-nitrophenyl ether (TOK) (1.8 to 1.1 mg/kg/ day, 9.2 to 5.2 mg/kg/day, and 46 to 26 mg/kg/day, respectively). The survival of the offspring was not affected at the 0 and 20 ppm dietary levels. At the 100 ppm dietary level the survival of the offspring to weaning was reduced and at the 500 ppm dietary level no offspring survived the neonatal period in the two breedings of the first generation. In further studies rats were dosed during pregnancy either by stomach tube or by adding TOK to the diet. The reduction in the number of surviving litters was caused by poorly developed lungs in the exposed groups. Technical TOK had the same effect as 99% pure TOK. Furthermore, 2,7-dichlorodibenzodioxin, which may be a contaminant of TOK, does not affect the maturation process of the lungs when given at a dose of 0.04 mg/kg/day on days 7 to 15 of gestation.

RELATIONSHIP BETWEEN DEPRESSION OF BRAIN OR PLASMA CHOLINESTERASE AND PARALYSIS IN CHICKENS CAUSED BY CERTAIN ORGANIC PHOSPHORUS COMPOUNDS.

Abstract A study has been made of the relationship between the inhibition of plasma or brain cholinesterase of the chicken and the paralytic syndromes caused by DFP, TOCP, malathion, ronnel, EPN, and Trithion. DDVP and Dipterex served as non-paralytic controls. TOCP was the only compound tested that was a specific inhibitor of brain cholinesterase. All compounds except EPN inhibited plasma cholinesterase. All compounds tested inhibited brain true and/or pseudocholinesterase. All paralytic compounds tested except DFP produced a prolonged inhibition of brain true and/or pseudocholinesterase which lasted for 5 to 17 days. It was concluded that no causative relationship exists between the prolonged inhibition of brain cholinesterase and the paralytic syndromes. The regeneration of brain cholinesterase after inhibition with DFP, Dipterex, or DDVP is probably due to protein synthesis de novo ; the prolonged inhibition of these enzymes after the administration of the other compounds may be due in part to the persistence of the inhibitor in the body.

Toxicity of fentin hydroxide to rats.

Abstract Fentin hydroxide (triphenyl tin hydroxide) was given in the diet to rats at the rate of 400 ppm. This amount reduced the food consumption and, within 7–34 days, caused death from starvation and hemorrhage in all tested rats. Dietary levels of 100 and 200 ppm reduced food consumption and weight gain, particularly during the first week. By week 7, the animals had adapted to these concentrations of the chemical, and the food consumption was the same as that of the controls. The food intake or weight gain was not affected in rats fed 50 ppm of fentin hydroxide for 276 days. After 64 days of dietary exposure at 200 or 100 ppm, reduced fertility was observed in male rats, but fertility improved later, and was comparable to that of the control rats by day 113. The difference was explained by the partial starvation which the animals suffered, particularly during the first week of the experiment. Gross and microscopic examination of rats fed fentin hydroxide at the rate of 200, 100, or 50 ppm for 276 days did not reveal changes in any organ that could be related to the compound.

Poisoning by organic phosphorus pesticides potentiated by phenothiazine derivatives.

Repeated administration of the phenothiazine derivatives chlorpromazine and promazine increased the toxicity of a single dose of parathion in male rats. In female rats, a single dose of 5 mg/kg of promazine increased the toxicity of a single dose of parathion, but had no apparent effect on the toxicity of a single dose of Phosdrin. Repeated dosage with chlorpromazine and atropine, or promazine and atropine, after administration of parathion at the same rate, resulted in a slightly higher mortality in female rats than did atropine or no treatment.

Rate of formationin vivo of the unreactivatable form of brain cholinesterase in chickens given DDVP or malathion

Abstract The half-time for the conversion of the reversibly inhibited form of the dimethyl phosphorylated cholinesterase to the irreversibly inhibited form of this enzyme in the brains of chickens given DDVP or malathion has been found to be 2 hr. The same half-time is observed in vitro in brain homogenates inhibited with DDVP or malaoxon, the active form of malathion.