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Biomedical subjects

D W Gaylor

Publications and source records attributed to D W Gaylor.

At least 109 records · Page 6Linked to original sources
PubMed1983

The use of safety factors for controlling risk.

Safety factors often are applied to animal bioassay data on toxic effects to establish dosage levels for which it is hoped there will be negligible deleterious effects on human health. A relationship between safety factors and disease risk is shown, making it possible to determine the size of the safety factor needed in order to maintain low levels of disease risk within animal populations. Also, it is demonstrated that "safe" doses obtained from the application of safety factors to the largest no-observable-effect level are similar to "safe" doses obtained by linear extrapolation.

Animal Diseases↗
PubMed1983

Estimators of relative risk for case-control studies.

The odds ratio from a case-control study of the "cumulative-incidence" type can be used as an estimate of the relative risk of a disease attributable to exposure to an agent only when the incidence of the disease is low. The odds ratio can be modified to obtain an accurate estimate of the relative risk, regardless of the incidence of the disease. This modification of the odds ratio can be performed with any one of four types of auxiliary information: overall probability of disease, probability of disease in the unexposed population, probability of disease in the exposed population, or overall probability of exposure. For "incidence density" case-control studies, the odds ratio equals the relative risk when the estimate of exposure in the comparison group can be considered to be an estimate of the overall probability of exposure in the population at risk. Under certain conditions, such "case-exposure" studies may be preferable to cohort studies and to cumulative-incidence case-control studies. The authors present an approach to hypothesis testing for crude and stratified data from a case-exposure study.

Abortion, Spontaneous↗
PubMed1982

The effect of dietary fortification on blood ethanol concentrations, caloric consumption, and weight gain during ethanol consumption in mice.

The objectives of this study were to determine the effects of dietary fortification on caloric consumption, weight gain, and blood ethanol concentration (BEC) in mice consuming ethanol-containing liquid diets. These diets have been used previously in this laboratory for ethanol fetotoxicity studies. To achieve these objectives, mice were adapted to a commonly used liquid mouse diet and randomly allocated to one of two experimental groups. One group received the liquid diet containing 4.1% (w/v) ethanol. The second group received the 4.1% w/v ethanol diet fortified with protein, carbohydrates, fats, vitamins, and minerals. Animals in both groups were monitored for weight changes and caloric intake. On days 5 and 12 of exposure (day 0- initial day), animals were sampled for BEC at 3-hour time intervals throughout a 24-hour period. All animals not previously sampled for BEC were also monitored every 3 hours for dietary intake. The animals receiving the fortified diet had a greater caloric consumption and weight gain during the 13 days of treatment than did the nonfortified diet animals. Blood ethanol levels determined on both sample days were significantly lower in the fortified diet group than in the nonfortified group. BEC values in both groups were significantly correlated with ethanol consumption during the previous 6-hour period. In conclusion, dietary modification could significantly alter the outcome of ethanol toxicity studies both by direct effects on growth and caloric/nutrient intake and by altering blood ethanol levels achieved during exposure.

Alcohol Drinking↗
PubMed1982

Influence of cause-of-death assignment on time-to-tumor analyses in animal carcinogenesis studies.

The importance of cause-of-death determination in an animal carcinogenesis study with respect to estimation of time-to-tumor distributions of internally occurring (occult) tumors is discussed. A nontechnical description of time-to-tumor estimation is presented. The information obtained from time-to-tumor estimation when cause-of-death designation was used is illustrated for liver tumors in female mice of the inbred strain BALB/cStCrlfC3Hf/Nctr from the ED01 study with N-2-fluorenylacetamide done at the National Center for Toxicological Research. A time-to-tumor analysis of reticulum cell sarcoma data from the same study has provided insight into some difficulties involved in routine case-by-case determination of cause of death. A more flexible system for assigning of cause of death to dead animals and cause of morbidity to moribund animals is described as a way to improve cause-of-death assignment.

2-Acetylaminofluorene↗
PubMed1980

Linear interpolation algorithm for low dose risk assessment of toxic substances.

In order to detect potential toxic effects of substances, relatively high doses generally are administered to relatively small numbers of laboratory animals. It is impossible to estimate low levels of disease incidence with precision at low environmental dose levels even with large numbers of laboratory animals. However, upper limits on risk can be obtained for convex dose response curves by linear interpolation between the lowest experimental dose level and zero. A simple mathematical algorithm is provided for low dose risk assessment from dose response data and the performance of this procedure is evaluated for a variety of toxicological data, including but not limited to carcinogenesis. The low dose confidence limits resulting from linear interpolation are similar to those obtained from the Armitage-Doll multistage model.

2-Acetylaminofluorene↗
PubMed1980

Effects of dose and time in a long-term, low-dose carcinogenic study.

Large numbers of female BALB/c StCrlfC3Hf/Nctr mice were exposed for up to 33 months to low doses of 2-acetylaminofluorene (2-AAF) under controlled conditions. The study design consisted of sacrifice intervals, life span, and discontinued dosing groups. Two separate and distinct endpoints, that is urinary bladder neoplasms and liver neoplasms, resulted in 2 different types of dose response relationships. Although bladder neoplasms exhibited a minimum effect level (or a nonlinear response) for specific conditions, the total results were consistent with a "no threshold concept." The late appearing liver neoplasms displayed a nearly linear type response that extrapolated directly to zero dose. Time of exposure was shown to be an important factor in that, as animals were sacrificed at 18, 24, and 33 months, a positive response was noted at the next lower dose as time was extended. Discontinuing dosing and sacrificing at 18 and 24 months also demonstrated the effects of exposure to the carcinogen 2-AAF. Induction of bladder neoplasms was shown to occur early in the study, but was dependent upon the continuous presence of 2-AAF. The liver neoplasms appeared very late in the study but were shown to be induced at a very early point in the exposures and did not require the continuous presence of the carcinogen in order to develop. A standard 18 month bioassay study, if conducted under the same conditions, would have classified this chemical as a weak acting carcinogen. These studies demonstrate the importance of the time factor in safety evaluation or risk assessment in carcinogenesis.

2-Acetylaminofluorene↗
PubMed1979

Accuracy of birth certificate data for detecting facial cleft defects in Arkansas children.

A comparison of facial cleft defects reported on birth certificates during the period 1943 to 1974 that were reported on birth certificates was made with records maintained by the Arkansas Crippled Childrens Services (CCS). A total of 506 cases were reported of which 331 (65%) were recorded on the birth certificate. Moreover, the accuracy of the reporting was not good. Only 243 (48%) cleft malformations were correctly classified on the birth certificate. Birth certificate information is an inadequate measure of the true facial cleft occurrence in Arkansas. Caution must be exercised when this data source is used in epidemiological surveys because over one-third of such defects were not recorded. These findings serve to reemphasize the national need to improve the quality of such vital health statistics sources.

Arkansas↗
PubMed1976

Reduced interlitter variability in rats resulting from a restricted mating period, and reassessment of the ""litter effect''.

Rats were mated for two or 15 hours and variability of day-12-embryos in weight, protein content, and [3H]thymidine incorporation was compared in the long mating period (LMP) and short mating period (SMP) groups by a 2-level nested analysis of variance. Variability in day-20 fetal weight was similarly compared. In both groups day-12 embryonic weight was relatively more variable than day-20 fetal weight, and variability was less in SMP than LMP animals for each comparison made, although statistical significance was attained only for thymidine incorporation. ""Litter effects'' were noted but not of the magnitude reported by other investigators. It was concluded that inappropriate statistical methods have encouraged the belief that among-litter variability usually exceeds within-litter fetal weight variability. The teratological implications of reduced development variability and the ""litter effect'' are discussed.

Abnormalities, Drug-Induced↗
PubMed1976

Teratological evaluation of FD&C red no.2-a collaborative government-industry study. I Introduction, experimental materials, and procedures.

Because of recent studies indicating possible embryolethality and teratogenicity of FD&C Red. No 2, and ad hoc committee was convened by the Food and Drug Administration to consider these questions. The committee suggested a collaborative study by three laboratories [Food and Drug Administration (FDA), Industrial Bio-Test Laboratories (IBT), and National Center for Toxicological Research (NCTR)] in which Red No. 2 was given at 200 mg/kg body weight, by gavage during days 0-19, 6-15, or 7-9 of gestation. FD*C Red No. 2 was also given at the same dose level via water bottle. Appropriate controls were utilized. FDA used Osborne-Mendel strain rats, IBT used Charles River strain also showed an increase in the same parameter for the same dose level and in addition showed a significant increase in the percentage of resorptions per litter. It was concluded that because of the inherent variation and the absence of an increase in abnormalities or other indications of embryotoxicity, there is reason to doubt that this effect is either biologically significant or reproducible.

Amaranth Dye↗
PubMed1976

Teratological evaluation of FD&C Red No. 2-a collaborative government -industry study. IV. NCTR's study.

Because of recent studies indicating possible embryolethality and teratogenicity of FD&C Red No. 2, an ad hoc committee was convened by the Food and Drug Administration to consider these questions. The committee suggested a collaborative study by three laboratories [Food and Drug Administration (FDA),Industrial Bio- Test Laboratories (IBT), and National Center for Toxicological Research (NCTR)] in which Red No. 2 was given at 200 mg/kg body weight, by gavage during days 0-19, 6-15, or 7-9 of gestation. FD&C Red No. 2 was also given at the same dose level via water bottle. Appropriate controls were utilized. FDA used Osborne-Mendel strain rats, IBT used Charles River, and NCTR used both strains. No significant increases in skeletal or visceral abnormalities were seen. No significant increase in resorptions was seen in the Osborne-Mendel strain, but the Charles River strain at IBT showed a showed a significant increase in litters with two or more resorptions after dams had been given 200 mg/kg at 0-19 days of gestation. The NCTR study on the Charles River strain also showed an increase in the same parameter for the same dose level and in addition showed a significant increase in the percentage of resorptions per litter. It was concluded that because of the inherent variation and the absence of an increase in abnormalities or other indications of embryotoxicity, there is reason to doubt that this effect is either biologically significant or reproducible.

Abnormalities, Drug-Induced↗
PubMed1976

Teratological evaluation of FD&C Red no. 2-a collaborative government -industry study. V. Combined findings and discussion.

Because of recent studies indicating possible embryolethality and teratogenicity of FD&C Red No. 2, anad hoc committee was convened by the Food and Drug Administration to consider these questions. The committee suggested a collaborative study by three laboratories [Food and Drug Administration (FDA), Industrail Bio- Test Laboratories (IBT), and National Center for Toxicological Research (NCTR)] in which Red No. 2 was given at 200 mg/kg body weight, by gavage during days 0-19, 6-15, or 7-9 of gestation. FD&C Red No. 2 was also given at the same dose level via water bottle. Appropriate controls were utilized. FDA used Osborne-Mendel strain rats, IBT used Charles River, and NCTR used both strains. No significant increases in skeletal or visceral abnormalities were seen. No significant increase in resorptions was seen in the Osborne-Mendel strain, but the Charles River strain at IBT showed a significant increase in litters with two or more resorptions after dams had been given 200 mg/kg at 0-19 days of gestation. The NCTR study on the Charles River strain also showed an increase in the same parameter for the same dose level and in addition showed a significant increase in the percentage of resorptions per litter. It was concluded that because of the inherent variation and the absence of an increase in abnormalities of other indications of embryotoxicity, there is reason to doubt that this effect is either biologically significant or reproducible.

Amaranth Dye↗
PubMed1970

Teratogenic evaluation of 2,4,5-T.

The herbicide 2,4,5-trichlorophenoxyacetic acid is teratogenic and fetocidal in two strains of mice when administered either subcutaneously or orally and in one strain of rats when administered orally. The incidences of both cystic kidney and cleft palate were increased in the C57BL/6 mice as well as the incidence of cleft palate in the AKR mice. The incidence of cystic kidney was also increased in the rats. In addition, an increase in the ratio of liver weight to body weight in the mouse fetus and the occurrence of hemorrhagic gastrointestinal tract in the rat fetus suggest that this compound also has fetotoxic properties.

Abnormalities, Drug-Induced↗
PubMed1965

Operations on the colon. The role of antibiotics in preoperative preparation.

A study was carried out on 183 patients in an attempt to evaluate the role of antibiotics in the preoperative preparation of the colon.Kanamycin, neomycin and a placebo were administered in a double-blind fashion during a 72-hour period preceding operation. In addition, mechanical cleansing of the bowel was done in all cases. Considering only the criteria of mortality and the incidence of postoperative wound and peritoneal infections in this preliminary report there was no apparent significant difference between patients receiving antibiotics and those receiving a placebo.

Aged↗
PubMedDate not supplied

A comparison of statistical methods for low dose extrapolation utilizing time-to-tumor data.

The assessment of health risks due to low levels of exposure to potential environmental hazards based on the results of toxicological experiments necessarily involves extrapolation of results obtained at relatively high doses to the low dose region of interest. In this paper, different statistical extrapolation procedures which take into account both time-to-response and the presence of competing risks are compared using a large simulated data base. The study was designed to cover a range of plausible dose response models as well as to assess the effects of competing risks, background response, latency and experimental design on the performance of the different extrapolation procedures. It was found that point estimates of risk in the low dose region may differ from the actual risk by a factor of 1000 or more in certain situations, even when precise information on the time of occurrence of the particular lesion of interest is available. Although linearized upper confidence limits on risk can be highly conservative when the underlying dose response curve is sublinear in the low dose region, they were found not to exceed the actual risk in the low dose region by more than a factor of 10 in those cases where the underlying dose response curve was linear at low doses.

Animals↗