In humans, diethyl phthalate was irritant to the eyes and to broken, but not intact, skin. One individual became sensitized following repeated contact with articles containing diethyl phthalate although attempts to induce skin sensitization in volunteers were unsuccessful. In the liquid form, the phthalate was mildly irritant to guinea-pig skin and rabbit eyes, and irritation to the respiratory passages and eyes of cats was seen following exposure to airborne diethyl phthalate. A low acute toxicity was reported in rats exposed orally. Central nervous system effects and damage to the spleen and kidneys occurred in laboratory animals given single injections of diethyl phthalate and the liver was affected in subjects exposed through dialysis equipment. Repeated feeding to rats caused blood effects and produced increases in several organ weights (including the testes and liver), liver peroxisomes (subcellular structures), and liver enzyme activities. Effects seen in rats and mice after repeated dermal exposures included increases in liver and kidney weights and changes in the liver tissue of mice. In cats inhaling the phthalate repeatedly, there were central nervous system effects and cellular changes in the blood, liver and kidneys.
In a multi-generation study, decreased sperm count and reduced litter size occurred in subsequent generations of mice fed diethyl phthalate. Repeated dietary administration to pregnant rats affected foetal development at maternally toxic doses; foetal development was also affected when pregnant rats were treated by repeated intraperitoneal injections. No evidence of carcinogenic activity has been found in rats exposed either orally (in limited studies) or dermally, although benign liver tumours have been seen in mice after repeated dermal administration. Diethyl phthalate caused chromosome damage to mammalian cells in culture but only in the presence of a metabolizing system. A number of investigators have reported evidence of weak mutagenicity in Ames bacterial tests.
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