Inhibition of hepatic microsomal enzymes by alkylating agents.
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Aging↗
Biomedical subjects
R G Tardiff
Publications and source records attributed to R G Tardiff.
Doses and lung burdens of environmental tobacco smoke constituents in nonsmoking workplaces.
This paper models nicotine dose and ultraviolet-absorbing particulate matter (UVPM) alveolar lung burden resulting from exposure to environmental tobacco smoke (ETS) for nonsmokers in workplaces where smoking was reported not to occur. Data were obtained from personal monitoring of ETS in 16 U.S. cities [Jenkins R.A., Guerin M.R., Palausky A., Counts R.W., Bayne C.K., and Dindal A.B. Determination of human exposure to environmental tobacco smoke (ETS): a study conducted in 16 U.S. cities. Draft final report by Oak Ridge National Laboratory for Center for Indoor Air Research, Linthicum, MD, 1996a; Jenkins R.A., Palausky A., Counts R.W., Bayne C.K., Dindal A.B., and Guerin M.R. Exposure to environmental tobacco smoke in sixteen cities in the United States as determined by personal breathing zone air sampling. J. Expos. Anal. Environ. Epidemiol. 1996b: 6(4): 473-502.]. This is a continuation of earlier analyses focusing on nonsmokers in smoking workplaces (SWs) [LaKind J.S., Graves C.G., Ginevan M.E., Jenkins R.A., Naiman D.Q., and Tardiff R.G. Exposure to environmental tobacco smoke in the workplace and the impact of away - from - work exposure. Risk Anal. 1999a: 19(3): 349-358; LaKind J.S., Jenkins R.A., Naiman D.Q., Ginevan M.E., Graves C.G., and Tardiff R.G. Use of environmental tobacco smoke constituents as markers for exposure. Risk Anal. 1999b: 19 (3): 359-373; LaKind J.S., Ginevan M.E., Naiman D.Q., James A.C., Jenkins R.A., Dourson M.L., Felter S.P., Graves C.G., and Tardiff R.G. Distribution of exposure concentrations and doses for constituents of environmental tobacco smoke. RiskAnal. 1999c: 19 (3): 375-390.]. Even though study participants characterized their workplaces as nonsmoking, some individuals reported observing cigarettes in the workplace. Individuals observing six or more cigarettes were excluded from the analysis on the grounds that they were in defacto SWs. Exposure to ETS was lower in nonsmoking than SWs, but even with this exclusion, exposure was not zero. Distributions were selected for each model input, and at least 2000 iterations of the model were made for each dose or lung burden characterization (e.g., for females, for males). In these nonsmoking workplaces (NSWs), neither nicotine nor UVPM concentrations were lognormally distributed. Hence, observed concentrations were used directly via bootstrap sampling (nicotine) or a constant number of times (UVPM) as input to the models. As in SWs, individuals from smoking homes (SHs) experienced greater exposure in NSWs to both nicotine and UVPM than did individuals from nonsmoking homes (NSH; P<0.001 ). The distributions of modeled nicotine dose and UVPM lung burden were highly skewed, with most individuals receiving relatively low exposure to ETS in the workplace. Comparing doses from NSWs modeled here to doses from SWs modeled previously, less difference between smoking and NSWs was apparent in UVPM levels than in nicotine levels. For average exposure, UVPM alveolar lung burdens were approximately 10-fold higher in smoking than NSWs, while average nicotine doses were 20-25 times higher in smoking than NSWs. These findings are in the range observed by other investigators and are partly explained by very low denominators in the ratios (i.e., very low levels experienced in NSWs). For upper bound exposure, the nonsmoking-to-smoking ratios remained about the same for UVPM. For nicotine, the upper bound ratios remained the same for people from NSHs but were halved for people from SHs.
Adult↗
Human exposure assessment. I: Understanding the uncertainties.
Exposure estimates produced using predictive exposure assessment methods are associated with a number of uncertainties that relate to the inherent variability of the values for a given input parameter (e.g., body weight, ingestion rate, inhalation rate) and to unknowns concerning the representativeness of the assumptions and methods used. Despite recent or ongoing consensus-building efforts that have made significant strides forward in promoting consistency in methodologies and parameter default values, the potential variability in the output exposure estimates has not been adequately addressed from a quantitative aspect. This is exemplified by remaining tendencies within federal and state agencies to use worst-case approaches for exposure assessment. In this study, range-sensitivity and Monte Carlo analyses were performed on several different exposure scenarios in order to illustrate the impact of the variability in input parameters on the total variability of the exposure output. The results of this study indicate that the variability associated with the example scenarios range up to more than four orders of magnitude when just some of the parameters are allowed to vary. Comparison of exposure estimates obtained using Monte Carlo simulations (in which selected parameters were allowed to vary over their observed ranges) to exposure estimates obtained using standard parameter default assumptions demonstrate that a default value approach can produce an exposure estimate that exceeds the 95th percentile exposure in an exposed population.
Child, Preschool↗
Human exposure assessment. II: Quantifying and reducing the uncertainties.
Alternative methods of human exposure assessment that reduce and/or allow quantification of the uncertainties associated with exposure estimates are surveyed and illustrated. These alternative approaches include (1) use of more appropriate exposure parameter default values rather than values that result in extreme exposure estimates; (2) incorporation of time-activity data to better define appropriate exposure duration values; (3) the use of reasonable exposure scenarios rather than the traditional Maximally Exposed Individual (MEI) approach; (4) the use of stochastic approaches such as Monte Carlo-based and information analysis-based methods; (5) use of bivariate analysis to identify the extent to which interdependencies between different exposure parameters affect the distribution of exposure estimates; (6) use of less-than-lifetime exposure and risk assessment; and (7) incorporation of physiological considerations relevant to absorbed dose estimation, including route-specific impacts, use of improved absorption factors, and application of pharmacokinetic models. Other ways to improve the exposure assessment process, including assuring statistical equivalency in comparing different exposure estimates and incorporation of sensitive subpopulation considerations are also discussed, as are key research needs.
Child↗
Correlation of human hepatotoxicants with hepatic damage in animals.
Substances that cause liver damage in humans were identified through a literature search conducted on Toxline and Medline. Using the same search strategy, species other than man were selected, in whom hepatic injury could be attributed to exposure to the identified substances. A total of 38 substances were identified as producing liver damage, manifested by either clinical chemistry or histopathology. The substances included 24 drugs, 9 industrial chemicals, 3 environmental agents, 1 pesticide, and ethanol. Twelve of the 36 compounds have been toxicologically evaluated in man, rodent, and non-rodent. Histopathologic liver damage was reported in all three species for 11 of these compounds. Only carbencillin produced histopathologic damage in man but not in either the rodent or non-rodent. Where clinical chemistry changes were reported for all three species categories, only eight substances induced similar reactions in all three species. Only with two substances did man and rodent react similarly (both positive), while the non-rodent was negative. The two substances were polychlorinated biphenyl (PCB) and tetrachlorethane. In the majority of the cases in which either or both histopathologic or clinical chemistry changes were reported for man or for the rodent or non-rodent, the changes that occurred were qualitatively similar. The rodent was as sensitive a predictor for hepatic effects as the non-rodent. Although it is impossible to predict how liver damage observed in a laboratory animal is correlated with human liver damage, hepatotoxicity in the rodent must be considered as indicative of potential hepatic damage in man.
Animals↗
In vitro percutaneous absorption of [14C] ethylene glycol.
The objective of this study was to determine the percutaneous absorption of ethylene glycol through human skin in vitro. The in vitro diffusion cells were of the flow-through design with 1 cm2 surface area. Three separate donor skin samples, taken from the thighs of white males, 16, 37, and 57 years old, were used and three replicates were performed for each experiment. Phosphate buffered saline, at a flow rate of three ml per hour, served as the receptor fluid. The human cadaver skin samples were dermatomed to 500 microns. [14C]-labeled ethylene glycol was applied to the skin surface in acetone vehicle at a dose of 8 micrograms/cm2. After 24-hr dermal exposure, 18.28 +/- 11.66% of the applied dose was recovered in the receptor fluid, 8.29 +/- 5.02% in the skin and 12.53 +/- 6.77% in the skin surface wash (total accountability was 39.11 +/- 7.23%). Individual difference existed (P < 0.05) for the three human skin sources. The combined skin and receptor fluid partitioning resulted in a potential absorbed dose of 26.57% relative to the 8 micrograms/cm2 applied dose for a 24-hr exposure duration. This represents a flux of approximately 2 micrograms/cm2/24 hr or 0.09 micrograms/cm2/hr for ethylene glycol. The maximum flux observed was 2.82%/hr/cm2 or 0.25 micrograms/cm2/hr.
Adolescent↗