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1245. Phthalates—metabolism and short-term toxicity
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THE CHEMICAL ENVIRONMENT
Tri-(2-ethylhexyl)phosphate (I) is one of a series of alkyl phosphates and phosphites that have proved useful as plastlcizers. Acute and short-term toxicity studies have now been carried out. Its acute oral LD5o in rats exceeded 36-8 g/kg, a figure comparable with other reported values of 37 and 39 g/kg for the acute oral LDso in this species. Low parenteral toxicity was also demonstrated. No significant acute eye hazard was revealed in rabbit tests but repeated dermal applications in rabbits caused desquamation, some fissuring wi,h haemorrhage and severe hyperkeratosis~ though single applications caused only erythema. The eye and skin tests revealed no systemic effects. Unlike tricresyl phosphate, I showed no demyelinizing action in chick tests, and is therefore not materially neurotoxic. 90-Day inhalation tests in dogs, monkeys and guinea-pigs demonstrated little untoward effect from exposure to 11-85 mg I/m 3, and behavioural studies in dogs and monkeys showed no outstanding departure from normality. A metabolic study m rats, using I labelled with phosphorus-32 (32p), revealed that a single inhaled dose was distributed rapidly in the lungs, stomach contents, brain and liver with lesser amounts in other organs and tissues. Faecal excretion of 32p was high and urinary excretion relatively low and there was some indication that I is degraded in the body. 1245. Phthalates--metabolism and short-term toxicity
Erickson, Nancy G. (1965). The metabolism of diphenyl phthalate and butylbenzyl phthalate in the beagle dog. Diss. Abstr. 26, 3014. We have previously referred to the low order of parenteral toxicity of phthalate plasticizers (Cited in F.C.T. 1967, 5, 116). In the present metabolic study, dogs excreted unchanged in the faeces 90% of single oral doses of 5 g/kg of diphenyl phthalate (DPP) or butylbenzyl phthalate (BBP). Of the remainder, 3-4 ~o was excreted in the urine as phthalic acid. Other urinary metabolites included phenol (free and conjugated) from DPP and conjugated benzyl alcohol from BBP. The formation of butyl alcohol from BBP was not established. When DPP or BBP was fed to dogs at a dietary level of 1,2 or 5 % for 90 days, no adverse effect was seen other than retardation of growth at the 5 % level, caused by restricted food intake.
THE CHEMICAL ENVIRONMENT 1246. Fate of indium
Auvergne, E., Caujolle, F. & Pitet, G. (1965). Localisation de l'indium chez la souris apr~s administration intraveineuse de sulfate d'indium. C.r. Sdanc. Soc. Biol. 159, 2067. Auvergne, E., Caujolle, F., Oustrin, J. & Voisin, M.-C. 0966). Intoxications exp6rimentales par l'indium. Annls Biol. clin. 24, 739. Indium (In) is a newcomer to these pages. After a single intravenous injection into mice of 11.25 mg/kg (i.e. 24-hr LDs0) of In sulphate, spectrographic estimations of the In content of the tissues were made in the following 1-30 days (Auvergne et al. 1965, cited above). Within 24 hr of administration, concentrations of In approximating to 10 pg/g tissue were found in liver, kidneys, spleen and long bone, but in general these concentrations fell progressively in the following 30 days. A relatively small uptake of In was observed in the heart, lungs, pancreas and testes, but the adipose tissue was devoid of In throughout the 30-day period. The authors conclude that these findings are consistent with the known interference of In with the blood-forming elements.
THE CHEMICAL ENVIRONMENT
Tri-(2-ethylhexyl)phosphate (I) is one of a series of alkyl phosphates and phosphites that have proved useful as plastlcizers. Acute and short-term toxicity studies have now been carried out. Its acute oral LD5o in rats exceeded 36-8 g/kg, a figure comparable with other reported values of 37 and 39 g/kg for the acute oral LDso in this species. Low parenteral toxicity was also demonstrated. No significant acute eye hazard was revealed in rabbit tests but repeated dermal applications in rabbits caused desquamation, some fissuring wi,h haemorrhage and severe hyperkeratosis~ though single applications caused only erythema. The eye and skin tests revealed no systemic effects. Unlike tricresyl phosphate, I showed no demyelinizing action in chick tests, and is therefore not materially neurotoxic. 90-Day inhalation tests in dogs, monkeys and guinea-pigs demonstrated little untoward effect from exposure to 11-85 mg I/m 3, and behavioural studies in dogs and monkeys showed no outstanding departure from normality. A metabolic study m rats, using I labelled with phosphorus-32 (32p), revealed that a single inhaled dose was distributed rapidly in the lungs, stomach contents, brain and liver with lesser amounts in other organs and tissues. Faecal excretion of 32p was high and urinary excretion relatively low and there was some indication that I is degraded in the body. 1245. Phthalates--metabolism and short-term toxicity
Erickson, Nancy G. (1965). The metabolism of diphenyl phthalate and butylbenzyl phthalate in the beagle dog. Diss. Abstr. 26, 3014. We have previously referred to the low order of parenteral toxicity of phthalate plasticizers (Cited in F.C.T. 1967, 5, 116). In the present metabolic study, dogs excreted unchanged in the faeces 90% of single oral doses of 5 g/kg of diphenyl phthalate (DPP) or butylbenzyl phthalate (BBP). Of the remainder, 3-4 ~o was excreted in the urine as phthalic acid. Other urinary metabolites included phenol (free and conjugated) from DPP and conjugated benzyl alcohol from BBP. The formation of butyl alcohol from BBP was not established. When DPP or BBP was fed to dogs at a dietary level of 1,2 or 5 % for 90 days, no adverse effect was seen other than retardation of growth at the 5 % level, caused by restricted food intake.
THE CHEMICAL ENVIRONMENT 1246. Fate of indium
Auvergne, E., Caujolle, F. & Pitet, G. (1965). Localisation de l'indium chez la souris apr~s administration intraveineuse de sulfate d'indium. C.r. Sdanc. Soc. Biol. 159, 2067. Auvergne, E., Caujolle, F., Oustrin, J. & Voisin, M.-C. 0966). Intoxications exp6rimentales par l'indium. Annls Biol. clin. 24, 739. Indium (In) is a newcomer to these pages. After a single intravenous injection into mice of 11.25 mg/kg (i.e. 24-hr LDs0) of In sulphate, spectrographic estimations of the In content of the tissues were made in the following 1-30 days (Auvergne et al. 1965, cited above). Within 24 hr of administration, concentrations of In approximating to 10 pg/g tissue were found in liver, kidneys, spleen and long bone, but in general these concentrations fell progressively in the following 30 days. A relatively small uptake of In was observed in the heart, lungs, pancreas and testes, but the adipose tissue was devoid of In throughout the 30-day period. The authors conclude that these findings are consistent with the known interference of In with the blood-forming elements.