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Biomedical subjects

J E Huff

Publications and source records attributed to J E Huff.

At least 55 records · Page 3Linked to original sources
PubMed1985

Malathion and malaoxon: histopathology reexamination of the National Cancer Institute's carcinogenesis studies.

In the early 1970s the National Cancer Institute (NCI) studied malathion and the oxygen analog, malaoxon, for possible carcinogenicity in rats and mice. The results from these long-term studies were reported in three NCI Technical Reports with the conclusions that neither chemical was shown to be carcinogenic in rodents. In response to the renewed public health interest and concern about the increasing use of malathion in agriculture and especially its use to eliminate Mediterranean fruit fly infestations in California and Florida during the 1980s, the National Toxicology Program (NTP) in consultation and agreement with the NCI reevaluated the histopathology of the NCI studies of malathion in Osborne-Mendel and Fischer 344 rats and of malaoxon in Fischer 344 rats. The NTP histopathology reexamination confirmed the original NCI interpretative conclusions that malathion was not carcinogenic. For the malaoxon study, the only difference between the original and subsequent interpretations was for C-cell neoplasms of the thyroid gland, in that the NTP concluded there was equivocal evidence of carcinogenicity for male and female F344 rats.

Animals↗
PubMed1985

Benzyl acetate carcinogenicity, metabolism, and disposition in Fischer 344 rats and B6C3F1 mice.

Carcinogenesis studies of benzyl acetate (a fragrance and flavoring agent) were conducted in F344 rats and B6C3F1 mice. The chemical was given in corn oil by gavage once daily, 5 days/week for 103 weeks, to groups of 50 animals of each sex and species. For rats the doses were 0, 250, and 500 mg/kg body weight and for mice the doses were 0, 500, and 1000 mg/kg. Mean body weights of control and dosed rats and mice were not affected adversely by benzyl acetate. The survival of control and low dose female mice was lower than that of the high dose group. A genital tract infection may have contributed to the reduced survival. No other significant difference in survival was observed for dosed rats or mice. Benzyl acetate was absorbed from the gastrointestinal tract of rats and mice, with approximately 90% of the administered dose recovered as various metabolites in the urine within 24 h. The primary metabolite was hippuric acid, with minor amounts of a mercapturic acid, and one or more unidentified metabolites. This capacity for absorption, metabolism, and disposition was unaffected by the amount or number of doses administered. Under the conditions of these studies, benzyl acetate administration was associated with an increased incidence of acinar cell adenoma of the exocrine pancreas in male F344/N rats. No evidence of carcinogenicity was found for female F344/N rats. For male and female B6C3F1 mice there was evidence of carcinogenicity, in that benzyl acetate caused an increased incidence of hepatocellular neoplasms (particularly adenomas) and squamous cell neoplasms of the forestomach.

Absorption↗
PubMed1985

Comparative chronic toxicities and carcinogenic potentials of 2-ethylhexyl-containing compounds in rats and mice.

Four compounds containing a 2-ethylhexyl moiety [di(2-ethylhexyl)phthalate (DEHP), di(2-ethylhexyl)adipate (DEHA), tris(2-ethylhexyl)phosphate (TEHP), and 2-ethylhexyl sulfate (EHS)] were tested for carcinogenic and other chronic and subchronic toxic effects in 90-day and 2-year studies in male and female Fischer 344 rats and B6C3F1 mice. The low generalized toxic potencies of the test chemicals allowed relatively high doses of all of these compounds to be administered. Despite differences in chemical structure, all four chemicals were related to increased occurrences of hepatocellular neoplasms, principally carcinomas, in female mice. DEHA and DEHP also induced hepatocellular neoplasms in male mice, while DEHP caused hepatocellular neoplasms in both male and female rats. No other neoplasms were considered to be unequivocally related to compound administration in these studies. There was a positive correlation between the magnitude of the hepatocarcinogenic response in female mice and the probability of a hepatocarcinogenic response in male mice and in male and female rats, suggesting quantitative differences in the carcinogenic potentials of these agents. These results suggest that compounds containing a 2-ethylhexyl moiety (and 2-ethylhexanol, by implication) may possess some carcinogenic potential, especially for the rodent liver. No other organ-specific toxic effects common to two or more test chemicals were observed in these studies.

Adipates↗
PubMed1985

Neoplasms observed in untreated and corn oil gavage control groups of F344/N rats and (C57BL/6N X C3H/HeN)F1 (B6C3F1) mice.

Control data on F344/N rats and (C57BL/6N X C3H/HeN)F1 (B6C3F1) mammary tumor virus-free mice from the National Toxicology Program (NTP) were examined to determine if animals receiving corn oil by gavage showed tumor incidences that differed from those of untreated control animals. Analyses of these data were adjusted for interlaboratory variability, time-related trends, and supplier effects. Two biologically significant effects were found: Male F344/N control rats receiving corn oil by gavage showed a higher (P less than .05) incidence of pancreatic acinar cell adenoma and a lower (P less than .001) incidence of leukemia (primarily mononuclear cell leukemia) than did the corresponding untreated controls. The increased incidences of pancreatic acinar cell adenoma seen in male rats administered corn oil by gavage were associated with elevated body weights observed in these animals relative to untreated controls. Female F344 rats and male and female B6C3F1 mice showed little or no evidence of a difference in tumor incidence between corn oil gavage-treated and untreated controls. A review of nearly 300 carcinogenesis studies done by the National Cancer Institute (NCI) and the NTP revealed that there were no corn oil gavage studies in which increased incidences of pancreatic acinar cell tumors or leukemia in male F344/N rats were the sole evidence of the carcinogenicity of a test chemical. Thus use of corn oil appears to have little impact on the interpretation of NCI-NTP carcinogenicity studies.

Animals↗
PubMed1984

Results from 86 two-year carcinogenicity studies conducted by the National Toxicology Program.

Five categories of evidence of carcinogenicity in rats and mice were used to group interpretative results on 86 chemicals studied in recent carcinogenicity tests carried out by the National Toxicology Program (NTP). Of these studies, 50% (43/86) were regarded as showing carcinogenic effects, 42% (36/86) gave no evidence of carcinogenicity, 6% (5/86) showed equivocal evidence of carcinogenicity, and 2% (2/86) were regarded as inadequate experiments. The liver was the most frequent site of cancer in male and female Fischer-344 rats and in male and female B6C3F1 mice. Male rats appeared more sensitive than female rats to the induction of neoplasia, while for mice the females seemed more responsive. The routes of administration yielding the highest percentage (80-83%) of positive studies were gavage and inhalation; approximately one-third of the feed, drinking water, and dermal studies showed carcinogenic effects. In feeding studies, overall survival in dosed and control groups were similar, while the majority of gavage studies showed significantly reduced survival in one or more dosed groups relative to the corresponding controls. The overall percentage of studies showing carcinogenic effects (50%) agrees closely with the rate reported by other investigators for nearly 200 earlier carcinogenicity experiments conducted by the National Cancer Institute.

Animals↗
PubMed1983

The carcinogenicity of di(2-ethylhexyl) phthalate (DEHP) in perspective.

The commonly used plasticizer di(2-ethylhexyl) phthalate (DEHP) was recently tested for chronic toxic potential by incorporation into the diet of rats and mice for approximately 2 yr. Upon reviewing the test results, the sponsoring organization concluded that DEHP was carcinogenic to the rats and mice, as indicated by increased occurrences of liver tumors in the DEHP-exposed animals in comparison to controls. Another group has disagreed with this conclusion, however, citing perceived methodological deficiencies and improper interpretations in the study, and has also suggested that rodents may not be adequate models of human response to DEHP. This communication compares the conduct of the DEHP bioassay favorably with state-of-the-art procedures in animal carcinogenicity testing and documents approval of the study interpretations by several independent peer review groups. The carcinogenic potential of DEHP is placed in perspective by evaluating the evidence for DEHP-induced tumors in rodent species in light of dose response relationships, other biochemical and toxicological effects of DEHP, and its comparative metabolism and disposition in rodent and primate species. A composite analysis of the currently available information indicates that DEHP has been shown to be carcinogenic to rodents in a valid chronic test, indicating that it should be considered as a potential carcinogen in humans, as well. Further experimental inquiry will be required, however, to accurately assess the potential health risks posed to humans by exposure to small amounts of this plasticizer.

Animals↗
PubMed1982

Carcinogenicity testing of phthalate esters and related compounds by the National Toxicology Program and the National Cancer Institute.

Five phthalate ester and related compounds (phthalic anhydride, phthalamide, di(2-ethylhexyl) phthalate, di(2-ethylhexyl) adipate and butyl benzyl phthalate) have been tested for carcinogenic effects in standard lifetime rodent feeding studies. Groups of 50 male and female rats and mice were fed diets containing various concentrations of the test chemicals for 102-106 consecutive weeks. The dietary concentrations were estimated to be maximally tolerated doses and half maximally tolerated doses. All animals that died during the study and all survivors at the end of two years were examined grossly and microscopically for the presence of tumors. The incidences of animals with tumors at a specific anatomic site in the treated groups and the controls were compared statistically. Neither phthalamide nor phthalic anhydride increased tumor incidences in rats or mice. Di(2-ethylhexyl) phthalate increased the incidences of liver tumors in rats and mice of both sexes, while di(2-ethylhexyl) adipate caused liver tumors in male and female mice, only. Butyl benzyl phthalate did not cause tumors in male or female mice, but the incidence of myelomonocytic leukemia in butyl benzyl phthalate-treated female rats was significantly greater than that in the controls. Chemically induced early deaths in the butyl benzyl phthalate-treated male rats precluded an evaluation of carcinogenic potential in this sex. Under the conditions of these tests, di(2-ethylhexyl) adipate was considered to be carcinogenic in both rats and mice and di(2-ethylhexyl) adipate was considered to be carcinogenic in mice. The evidence for carcinogenic effects of butyl benzyl phthalate in female rats was judged to be equivocal because of the variable nature of the incidence of myelomonocytic leukemia in Fischer 344 rats. Phthalamide and phthalic anhydride did not exhibit carcinogenic effects in these studies.

Animals↗
PubMed1980

Long-term hazards of polychlorinated dibenzodioxins and polychlorinated dibenzofurans.

During January 10-11, 1978 in Lyon, France, a joint National Institute of Environmental Health Sciences/International Agency for Research on Cancer ad hoc Working Group considered and discussed the feasibility of coordinating epidemiological studies on the long-term hazards associated with the chlorinated dibenzo-p-dioxins and chlorinated dibenzofurans (PCDDs and and PCDFs). Nineteen invited scientists from eight countries presented introductory working papers summarizing the most up-to-date and relevant information available from their individual programs. This report represents the collective views and scientific opinions of the Working Group. The greater part of this document comprises epidemiological studies related to episodes of human exposures. The review begins with a brief section concerning possible routes of human exposure, an overview of the pertinent chemical characteristics, and the salient toxicological properties of the structurally similar PCDDs/PCDFs. The Working Group report ends with recommendations for future activities.

Abnormalities, Drug-Induced↗
PubMed1980

DDT and cancer.

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Animals↗