Failure of pure 1-naphthylamine to induce bladder tumors in dogs.

1-Naphthylamine was administered p.o. to beagles for approximately 9 years at a daily dose of 15 mg/kg (5 days a week). At autopsy, no tumors or other pathological changes were observed in the bladders of any of these animals. With the possible exception of the excessive accumulation of lipofuscin in the hepatocytes of these dogs, no test compound-related pathological changes in other tissues of the body were observed. Analysis of the urine revealed the presence of small amounts of N-oxidation products (1-nitrosonaphthalene plus N-hydroxy-1-naphthylamine), ranging from 2.85 to 125 microgram, following a dose of 1-naphthylamine. The theoretical significance of these findings is discussed.

Di(4-aminophenyl)-methane (MDA): 4-7 year dog feeding study.

9 pure bred female beagles ingested purified or crude MDA (in 70 mg doses on 3 days of the week) over periods ranging from 3 years, 11 months to 7 years, 2 months. Total quantities of MDA ingested ranged from 39.98 g to 66.92 g/dog, or from approx. 4.0 to 6.26 g/kg body wt. Purified and crude MDA in the doses administered produced similar effects: (a)occasional loss of body weight followed by rather prompt recovery while treatment was interrupted; (b) no specific effect on blood sugar, BUN, creatinine, uric acid, total protein, albumin and a questionable effect on alkaline phosphatase activity; (c) from moderate to severe gross and micropathological changes in the liver, less severe effects in the kidneys and spleen, and occassionally gross or micropathological changes in other organs. Purified and crude MDA did not produce tumors of the urinary bladder or liver.

Liver cancer deaths in the continental USA from 1930 to 1972.

Since 1944 the general U.S. population has been absorbing organochlorine pesticides, which have recently been largely banned because of a concern that they would cause or contribute to the production of liver cancer. This survey is related to the quantities of these pesticides used and the incidence of liver cancer deaths in the U.S. from 1930 to 1972.

Determination of organochlorine pesticides in the tissues of the black mullet (Mugil cephalus) and the silver mullet (Mugil curema).

The black or silver mullet is a suitable fish for determining the degree and type of local water pollution. In contrast to the great barracuda which we studied earlier, mullet did not lose significant quantities of body fat and DDT-type pesticides at the expense of the developing gonads.

Dieldrin and DDT in the tissues of mice fed aldrin and DDT for seven generations.

Seven-Generation Study (P-F6): The concentration and total retention of dieldrin or p,p'-DDT and metabolites were determined in the total carcass of Swiss-Webster mice fed dietary supplements of aldrin 5 or 10 ppm, or DDT 100 ppm, to age 260 days. All groups showed a significant increase in total body retention (and concentration) of dieldrin or total DDT in the total carcass of the F1, F2, and F3 generations. Generally, these increases were related directly to increases in total body lipids, when compared with the P generations. The control (pesticide-free) diet was fed to all F4 generation experimental mice from weaning to age 260. The pesticides absorbed by these animals while in utero and via lactation were found, at the time of sacrifice, to have been excreted completely. When the experimental diets were resumed with the weanlings of the F2 generations, a repetition of the general findings in the P and F1 generations was noted-demonstrating that pesticide retention and total body lipids are closely interrelated, and that a high body lipid content favors a high retention rate of these fat-soluble pesticides. These results support our earlier studies in rats (Deichmann et al., 1972) and investigations with cirrhotic human livers with severe fatty infiltration (Oloffs et al., 1974). Conception became more delayed with each succeeding generation, requiring some degree of "selective" breeding of the F4, F5, and F6 generations.