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D W Gaylor

Publications and source records attributed to D W Gaylor.

113 records · Page 7Linked to original sources
PubMedDate not supplied

Response to the society of toxicology task force re-examination of the ED01 study.

This communication has re-examined and justified certain of the NCTR's analyses and recommendations from the ED01 Study, which were either misunderstood or misinterpreted by the SOT Task Force. In addition, we have shown that some of the Task Force's own analyses and interpretations are subject to review on scientific grounds. The Task Force's rejection of the linear extrapolation method recommended by the NCTR was stated because of a suspected force-fitting of a linear model to data, an approach that is not part of the NCTR procedure. In suspecting a protective effect of 2-AAF against bladder tumors, the Task Force used an inappropriate model that overpredicted the background bladder tumor rate in control mice. Contrary to the Task Force's belief, a failure to account adequately for time to tumor response was more characteristic of analyses performed by the Task Force rather than those performed by the NCTR. The Task Force's questioning of the multistage model for risk assessment was based on its use of inappropriate, crude tumor data rather than upon NCTR's use of the multistage model with time-adjusted tumor data. The Hartley-Sielken model did not fit the ED01 tumor data as well as the Task Force had presumed. In a risk extrapolation comparison by the Task Force, a coarse time partition of the ED01 data that had been questioned by the Task Force actually produced more stable results than a finer partition proposed by the Task Force. Another problem in the Task Force report concerns the change of protocol. Instead of resulting in a loss of strength as anticipated by the Task Force, the change of protocol during the ED01 Study resulted in an increase in information as alluded to by the Task Force. If the Task Force's proposal for restricting the length of feeding studies had been followed in the ED01 Study, most of the dose related tumor information would not have been obtained. Also, the Task Force's belief that low doses of 2-AAF had some effect on the prevention of early death was not supported by a statistical analysis. In summary, the review conducted by the SOT Task Force contained some misleading representations of the data from the ED01 Study and statements that showed a misunderstanding of NCTR's analyses of the study.

Aging↗
PubMedDate not supplied

Controlled genetic variation in a subchronic toxicity assay: susceptibility to induction of bladder hyperplasia in mice by 2-acetylaminofluorene.

Five different dose levels of 2-acetylaminofluorene (2-AAF) were fed to weanling mice of 4 different genotypes from three unrelated F1 hybrids for 13 wk to determine differences in susceptibility to induction of bladder hyperplasia. Differences in the prevalence of hyperplasia per se and in the average grade of hyperplasia were interpreted as indicating greater susceptibility. On this basis, males of all genotypes were more susceptible than females. Among the genotypes, (AEX YS)F1 mice (AY) were most susceptible, followed closely by yellow A vy/A(BALB/cXVY)F1 mice (CV). Agouti A/a(BALB/cXVY)F1 mice were less susceptible than their yellow siblings and similar to the (C57BL/6XC3H)F1 mice. Neither body weight gain nor any of the biochemical parameters measured appeared to be affected at any dose level of 2-AAF. However, quantitative differences in several biochemical characteristics were detected among the genotypes. Serum gamma-glutamyl transpeptidase activity was higher in the AY mice than in the other hybrids. Among the CV mice, the yellow animals had lower glutathione S-transferase (GST) activity than their agouti siblings. Hepatic GST activity was lower in CV mice than in either of the other hybrids. Hepatic cytochrome P-450 and bs activities were similar in all hybrids.

2-Acetylaminofluorene↗
PubMedDate not supplied

Risk estimation--an overview: disease risk estimation based upon animal bioassays.

Much more could be written about the issues addressed here, as well as about issues that are not even mentioned. The goal was to present a brief overview of some of the techniques and issues in quantitative health risk assessment based upon animal data. Hopefully, this overview will provoke some attention to specific in risk assessment that require more research. Perhaps the bibliographic references given will lead to other papers.

Animals↗
PubMedDate not supplied

Urinary bladder neoplasms induced in BALB/c female mice with low doses of 2-acetylaminofluorene.

Large numbers of female BALB/c mice were exposed to low levels of 2-acetylaminofluorene (2-AAF) in the diet. The dose response for urinary bladder neoplasms exhibited a shallow trend to low doses which increased sharply at the higher doses. The dose response over the entire dosage range gave the impression of a "threshold" type response below the mid-doses. Since the tumor incidence at the lower doses was less than 1.0 percent, relatively few urinary bladder tumors occurred. Thus, it was deemed advisable to re-examine noninvasive or early invasive bladder carcinomas and to study the dose response for only the "unequivocal" urinary bladder tumors. Examination of the dose response curves for "unequivocal" urinary bladder tumors showed a positive trend over the low end of the dose range. As a further check, an analysis was conducted on only invasive or metastasizing bladder carcinomas. In this case, there was no significant low dose trend. Thus, the shape of the low dose response curve for bladder carcinomas remains uncertain.

2-Acetylaminofluorene↗