摘要:

In order to predict the exhaled breath concentration of chloroform in individuals exposed to chloroform while showering, an existing physiologically based pharmacokinetic (PB‐PK) model was modified to include a multicompartment, PB‐PK model for the skin and a completely mixed shower exposure model. The PB‐PK model of the skin included the stratum corneum as the principal resistance to absorption and a viable epidermis which is in dynamic equilibrium with the skin microcirculation. This model was calibrated with measured exhaled breath concentrations of chloroform in individuals exposed while showering with and without dermal absorption. The calibration effort indicated that the expected value of skin‐blood partitioning coefficient would be 1.2 when the degree of transfer of chloroform from shower water into shower air was 61%. The stratum corneum permeability coefficient for chloroform was estimated to be within the range of 0.16‐0.36 cm/hr and the expected value was 0.2 cm/hr. The estimated ratio of the dermally and inhaled absorbed doses ranged between 0.6 and 2.2 and the expected value was 0.75. These results indicate that for the purposes of risk assessment for dermal exposure to chloroform, a simple steady‐state model can be used to predict the degree of dermal absorption and that a reasonable value of skin permeability coefficient for chloroform used in this model would be 0.2 cm/hr. Further research should be conducted to compare the elimination of chloroform via exhaled breath when different exposure routes are being compared. The model results from this study suggest that multiple measurements of exhaled breath concentrations after exposure may be necessary when making comparisons of breath concentrations that involve different expo

ISSN:0272-4332    

DOI:10.1111/j.1539-6924.1993.tb00728.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Communities across the United States are examining the manufacture, use, transport, and storage of hydrogen fluoride (HF) near residential areas as a consequence of a major release of HF in Texas in 1987. Reference exposure levels for routine and accidental HF emissions are calculated using existing animal and human data. The approach employs a logprobit extrapolation of concentration‐response data to the 95% lower confidence limit on the toxic concentration producing a “benchmark dose” of 1% response (TC01), called a practical threshold. Species‐specific and chemical‐specific adjustment factors are applied to develop exposure levels applicable to the general public. Using this method, the 1‐hr reference exposure level to protect the public against any irritation from a routine emission (REL‐1) is 0.7 ppm and the level to protect against severe irritation from a once‐in‐a‐lifetime (REL‐2) release is 2 ppm. This approach is compared to a modified “uncer

ISSN:0272-4332    

DOI:10.1111/j.1539-6924.1993.tb00729.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

The development and application of appropriate physiologically based pharmacokinetic (PBPK) models of chemical contaminants will provide a rational basis for risk assessment extrapolation. Trichloroethylene (TCE) is a widespread contaminant found in soil, groundwater, and the atmosphere. Exposures to TCE and its metabolites have been found to be carcinogenic in rodents. In this study, a PBPK model for TCE and its major metabolite, trichloroacetic acid (TCA), is developed for humans. The model parameters, estimated from the relevant published literature on human exposures to TCE and its metabolites, are described. Key parameters describing the metabolism of TCE and the kinetics of TCA were estimated by optimization. The optimization was accomplished by simultaneously matching model predictions to observations of TCE concentrations in blood and exhaled breath, TCA plasma concentrations, and urinary TCA excretion from five published studies. The optimized human PBPK model provides an excellent description of TCE and TCA kinetics. The predictions were especially good for TCA plasma concentrations following repeated TCE inhalation, an exposure scenario similar to that occurring in the workplace. The human PBPK model can be used to estimate dose metrics resulting from TCE exposures and is therefore useful when considering the estimation of human health risks associated with such exposures.

ISSN:0272-4332    

DOI:10.1111/j.1539-6924.1993.tb00730.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Trichloroethylene (TCE) is a widespread environmental pollutant. TCE is classified as a rodent carcinogen by the U.S. Environmental Protection Agency (EPA). Using the rodent cancer bioassay findings and estimates of metabolized dose, the EPA has estimated lifetime exposure cancer risks for humans that ingest TCE in drinking water or inhale TCE. In this study, a physiologically based pharmacokinetic (PB‐PK) model for mice was used to simulate selected gavage and inhalation bioassays with TCE. Plausible dose‐metrics thought to be linked with the mechanism of action for TCE carcinogenesis were selected. These dose‐metrics, adjusted to reflect an average amount per day for a lifetime, were metabolism of TCE (AMET, mg/kg/day) and systemic concentration of TCA (AUCTCA, mg/L/day). These dose‐metrics were then used in a linearized multistage model to estimate AMET and AUCTCA values that correspond to liver cancer risks of 1 in 1 million in mice. A human PB‐PK model for TCE was then used to predict TCE concentrations in drinking water and air that would provide AMET and AUCTCA values equal to the predicted mice AMET and AUCTCA values that correspond to liver cancer risks of 1 in 1 million. For the dose‐metrics, AMET and AUCTCA, the TCE concentrations in air were 10.0 and 0.1 ppb TCE (continuous exposure), respectively, and in water, 7 and 4 μg TCE/L,

ISSN:0272-4332    

DOI:10.1111/j.1539-6924.1993.tb00731.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

This note suggests the use of Bézier curves to model probability distributions on computers. This represents an approach completely different from the current practice, which mostly employs parametric families or piece‐wise polynomials. The Bézier curves combine simplicity and flexibility with an easy manipulation method, allowing more accurate curves to be modeled to d

ISSN:0272-4332    

DOI:10.1111/j.1539-6924.1993.tb00732.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Seven criteria are presented for use in evaluating communications designed to explain the magnitude of a risk. The criteria are: (1)comprehension(Does the audience understand the content of the communication?); (2)agreement(Does the audience agree with the recommendation or interpretation contained in the message?); (3)dose‐response consistency(Do people facing a higher dose of a hazard perceive the risk as greater and/or show a greater readiness to take action than people exposed to a lower dose of this hazard?); (4)hazard‐response consistency(Do people facing a hazard that is higher in risk perceive the risk as greater and/or show a greater readiness to take action than people exposed to a hazard that is lower in risk?); (5)uniformity(Do audience members exposed to the same level of risk tend to have the same responses to this risk?); (6)audience evaluation(Does the audience judge the message to have been helpful, accurate, clear, etc.?); and (7)types of communication failures(When different types of failures are possible, are the failures that occur generally of the more acceptable variety?). Each of these criteria is illustrated with data collected in a test of message formats designed to explain the risk presented by radon gas in a h

ISSN:0272-4332    

DOI:10.1111/j.1539-6924.1993.tb00733.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

ISSN:0272-4332    

DOI:10.1111/j.1539-6924.1993.tb00734.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

ISSN:0272-4332    

DOI:10.1111/j.1539-6924.1993.tb00735.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY