Transplacental Toxicity and Carcinogenesis Studies in Rats with Hexamethylenetetramine

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Abstract
In a previous paper (Fd Cosmet. Toxicol., 6: 707–715, 1968) it was reported that hexamethylenetetramine (HMT) had no carcinogenic activity in long-term experiments in mice and rats. In the present study, 12 ♀ and 6 ♂ Wistar rats were given 1% HMT in the drinking water starting 2 weeks before mating. The females were kept under treatment during pregnancy and lactation. A similar untreated group of 12 ♀ and 6 ♂ served as control. Twelve treated females and eleven controls became pregnant and gave birth to 124 and 118 babies respectively; no malformations were noted. From these animals, 24 for each sex were continued on the 1% HMT up to the 20th week of age or were kept untreated. The body weight of treated animals was significantly lower than that of controls one, only up to the 9th week of age for the males and up to the 13th week for the females. At the end of the treatment both groups were sacrificed; the weight of organs was identical in the treated and control animals; there were no gross or histological pathology. In a second experiment, rats were given 1% HMT in the drinking water for 3 successive generations, up to the age of 40 weeks in the F1 and F2 groups and of 20 weeks for F3. The three groups were composed of 13 ♂ and 7 ♀, 15 ♂ and 11 ♀, 12 ♂ and 12 ♂, respectively. In addition, a group of 16 ♂ and 16 ♀ descendants of 2% HMT treated parents, were given 2% HMT for 50 weeks. A group of 48 ♂ and 48 ♀ served as untreated controls. All groups were kept under observation for over 2 years of age. No evidence of carcinogenicity was found in any of the HMT-treated groups.