Dan W. Dalgard

Effects of long-term oral administration of DDT on nonhuman primates

Abstract Because of reports on tumorigenic activity in different animal species exposed to DDT a decision was made in 1969 to evaluate the long-term effects of DDT on 24 cynomolgus and rhesus monkeys. DDT (20 mg/kg) was given in the diet for 130 months, followed by an observation period that ended in 1994. The two cases of malignant tumor detected in the DDT group included a metastatic hepatocellular carcinoma in a 233-month-old male and a well-differentiated adenocarcinoma of the prostate in a 212-month-old monkey. Benign tumors detected in the DDT group included three cases of leiomyoma, two of which were uterine and one, esophageal. No tumor was detected in the control group of 17 monkeys. Fatty changes in the liver were observed in 52.9% of the DDT group and 29.4% of the control group. More specific signs of hepatotoxicity were documented microscopically in seven DDT monkeys. Severe tremors and histological evidence of CNS and spinal cord abnormalities were observed in six DDT monkeys. The present findings show clear evidence of hepatic and CNS toxicity following long-term DDT administration to cynomolgus and rhesus monkeys. However, the two cases involving malignant tumors of different types are inconclusive with respect to a carcinogenic effect of DDT in nonhuman primates.

Olfactory neuroepithelioma in a cynomolgus monkey (Macaca fascicularis).

This is a report of an olfactory neuroepithelioma occurring in a male cynomolgus monkey (Macaca fascicularis). It is not possible to state whether this tumor was spontaneous or related to the experimental procedures carried out in this animal.

Lack of Carcinogenicity of 2‐Amino‐3,8‐dimethylimidazo[4,5‐f]quinoxaline (MeIQx) in Cynomolgus Monkeys

The carcinogenic potential of 2‐amino‐3,8‐dimethylimidazo[4,5‐f]quinoxaline (MeIQx) was evaluated in cynomolgus monkeys. The animals received MeIQx, beginning at the age of one year, at doses of 10 or 20 mg/kg body weight by gavage five times a week for 84 months and were autopsied 8 months thereafter. Although sporadic development of aberrant crypt foci in the colon and glutathione S‐transferase π‐positive foci in the liver as well as hyper plastic changes of the lymphatic tissue in the lung and gastro‐intestinal tract were observed in several monkeys, this was not treatment‐related. No neoplastic or preneoplastic lesions were found in other organs. Serum chemistry data and organ weights were also within the normal ranges. From these data, it is concluded that MeIQx is not carcinogenic in the cynomolgus monkey under the conditions examined. This lack of carcinogenicity is probably related to the poor activation of MeIQx due to the lack of constitutive expression of CYP1A2 as well as an inability of other cytochrome P450s to catalyze N‐ hydroxylation of MeIQx in the cynomolgus monkey.

Lactose malabsorption in two sibling rhesus monkeys (Macaca mulatta).

Observation of two sibling rhesus monkeys, Macaca mulatta, indicated that they were intolerant to lactose. While on a lactose formula the monkeys had severe diarrhea and weight loss but were otherwise healthy. When a lactose-free formula was instituted, the diarrhea abated and there was a steady weight gain.