DDT tissue retention: sudden rise induced by the addition of aldrin to a fixed DDT intake.

The oral administration of aldrin to male and female beagles, whose diet already included a fixed, regular oral dosage of DDT, resulted in a dramatic rise in the concentrations of DDT, DDE, and DDD in blood and fat.

Cocarcinogenic interaction between D,L-tryptophan and 4-aminobiphenyl or 2-naphthylamine in dogs.

Administration of a dietary supplement of 6 g D,L tryptophan/day for 4 1/2 years following the administration of a single dose of 50 mg 4-aminobiphenyl/kg produced a bladder tumor in 1 of 4 beagle dogs. No tumors were observed in 6 dogs given the same dose of 4-aminobiphenyl without supplemental tryptophan. In a second experiment, administration of a supplement of 6 g D,L-tryptophan/day for 3 years following the administration of 5 mg 2-naphthylamine/kg/day for 30 days produced bladder tumors in 2 of 4 dogs. No tumors or other bladder pathology was produced by treatment of 4 dogs with this dose of 2-naphthylamine alone. Dogs given D,L-tryptophan alone developed no bladder tumors, but in most dogs receiving tryptophan the "tryptophan effect", i.e., a darkly stained mucosa with white areas of focal hyperplasia, was observed. Both experiments suggest a role of D,L-tryptophan as a cocarcinogen or promotor in the induction of bladder cancer.

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.

Failure of the N-oxodized metabolites of some carcinogenic amines to induce tumors in normal and wounded rat skin.

The skin of Osborne-Mendel and Sprague-Dawley rats was treated by repeated topical application of 1- and 2-naphthylamine, 4-biphenylamine and their corresponding N-arylhydroxylamine and nitroso derivatives for 52 weeks. In addition, the possibility of enhancing the susceptibility of the skin to the tumor induction by periodic wounding at the site of compound application was investigated in the Sprague-Dawley strain. The animals were observed for an additional year after which all survivors were sacrificed. No skin tumours were elicited in any of the rats although a small number of systemic tumors at sites distant from the area of application were observed in the Osborne-Mendel strain. No discernable increase in the sensitivity of the skin as a consequence of wounding to the carcinogenic effect of the compounds tested were observed.

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.

Improvements in the NIOSH registry of toxic effects of chemical substances.

Subsequent to the publication of the 1977 edition of the NIOSH Registry of Toxic Effects of Chemical Substances (RTECS), several additions and changes were introduced that substantially improved the content and accessibility of the RTECS data file. Content additions included primary irritation data for both skin and eyes, in vitro mutagenicity data, and citations to toxicology review articles and to the Toxic Substances Control Act inventory. Also undertaken was a re-evalution of existing tumorigenic entries based on revised selection criteria. Accessibility to RTECS data has been facilitated by the introduction of on-line interactive computer searching, and the preparation and distribution of Computer Output Microfiche (COM-fiche) and magnetic tape copies of the file which supplement the annual publication.