Experimental Human Exposure to Trichloroethylene

Stewart, Richard D.; Dodd, Hugh C.; Gay, Harold H.; Erley, D. S.

doi:10.1080/00039896.1970.10665543

Cited by 105 publications

(50 citation statements)

References 10 publications

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“…After the clearance of this compartment, the breath concentration may follow the emptying of a compartment with a longer half-time, at a rate that indicates an integrated exposure over a longer period. These results are consistent with studies of breath concentrations after exposure to trichloroethylene (8), and they support the view that breath samples taken on the morning after exposure provide a more useful index of exposure than those taken at the end of a workshift.…”

Section: Occupational Exposuresupporting

confidence: 81%

Breath concentration as an index of the health risk from benzene. Studies on the accumulation and clearance of inhaled benzene.

Berlin¹,

Jc²,

Gullberg³

et al. 1980

Scand J Work Environ Health

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Section: Occupational Exposuresupporting

confidence: 81%

Breath concentration as an index of the health risk from benzene. Studies on the accumulation and clearance of inhaled benzene.

Berlin¹,

Jc²,

Gullberg³

et al. 1980

Scand J Work Environ Health

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“…For rats, the blood concentration of DCA (a = 1.14) seems to be systematically underpredicted. For (24) data. This leads to high residual errors (a = 0.79).…”

Section: Resultsmentioning

confidence: 99%

“…The concentration of TCE in the air chamber was measured. The same study also exposed four groups of 3 [21][22][23][24]. The venous blood concentrations of TCE and TCA were measured at various times.…”

Section: Methods Datamentioning

confidence: 99%

Statistical analysis of Clewell et al. PBPK model of trichloroethylene kinetics.

Bois

2000

Environ Health Perspect

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A physiologically based pharmacokinetic model for trichloroethylene (TCE) in rodents and humans was calibrated with published toxicokinetic data sets. A Bayesian statistical framework was used to combine previous information about the model parameters with the data likelihood, to yield posterior parameter distributions. The use of the hierarchical statistical model yielded estimates of both variability between experimental groups and uncertainty in TCE toxicokinetics. After adjustment of the model by Markov chain Monte Carlo sampling, estimates of variability for the animal or human metabolic parameters ranged from a factor of 1.5-2 (geometric standard deviation [GSDI). Uncertainty was of the same order as variability for animals and higher than variability for humans. The model was used to make posterior predictions for several measures of cancer risk. These predictions were affected by both uncertainties and variability and exhibited GSDs ranging from 2 to 6 in mice and rats and from 2 to 10 for humans. The recent development of a comprehensive physiologically based pharmacokinetic (PBPK) model of trichloroethylene (TCE) disposition and metabolism in mice, rats, and humans (1) offers us the opportunity to examine issues of variability and uncertainty for that solvent. In particular, uncertainties in prediction of various cancer dose metrics deserve to be computed, since they could be directly used as input for improved risk assessments.PBPK modeling provides a strong mechanistic basis for prediction of disposition and metabolism of toxicants. Yet much uneasiness remains with the use of these models in toxicology (2). Similarly, as discussed in a recent review and an accompanying commentary, PBPK modeling has not seen the development it promised for therapeutic compounds (3,4). The reason for this essentially lies in the lack of statistical methods for calibrating these models. Because of individual variability and uncertainty, many parameters are difficult to measure accurately even for inbred animal strains. Using input parameters or presenting results in the form of a single value can therefore be very misleading (5). In the absence of rigorous statistical treatment, inference presented by PBPK modeling is largely empirical, hypotheses are left unvalidated, and predictions lack realistic measures of uncertainty. This state of affairs is unfortunate, when considering the consequences (for public health and national welfare) of the decisions made using these models.Obviously, correct statistical treatment of PBPK models is difficult, since these are large nonlinear models with relatively small data sets and a high degree of uncertainty and biological variability (6). It is also essential to respect the fundamental specificity of PBPK models, i.e., their high prior information content, which they provide through the opportunity to use physiological information on parameter values. Yet, although several parameters have physiological meaning and a narrow range of possible values, others-often specific of the com...

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“…From a survey of a factory where TRI levels were higher than 10 ppm in 40°, of about 200 air samples collected, Lilis et al (1969) found that the most common complaints of the workers were dizziness (88%), headache (74%), fatigue (68%), irritability (56%) and nausea (43%). In contrast, Stewart et al (1970) reported from controlled exposures of volunteers at 200 ppm that the only troublesome response was mild fatigue and sleepiness. Because of technical limitation of the days of the studies cited, the levels reported in factory surveys may not mean the breath zone air concentration but rather indicate the levels in the grab-sampled workroom air.…”

Section: Discussionmentioning

confidence: 79%

Increased subjective symptom prevalence among workers exposed to trichloroethylene at sub-OEL levels.

Liu

Jin

Chen

et al. 1988

Tohoku J. Exp. Med.

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Over 100 workers exposed to trichloroethylene (TRI) mostly at less than 50 ppm during the production or vapor degreasing operation and about an equal number of the non-exposed control workers were examined for subjective symptoms, hematology, serum biochemistry, and sugar, protein and occult blood in urine. Essentially all the clinico-laboratory tests stayed normal, and there was no significant difference in the findings between the exposed and the controls. Thus, no clinically significant effects of TRI exposure were found in the blood and liver functions among the exposed workers as compared with the controls. The prevalence of the subjective symptoms was, however, significantly higher in the exposed group than in the controls, and dose-response relationship could be established in some selected symptoms such as nausea, heavy feeling in the head, forgetfulness, tremor in extremities, cramp in extremities and dry mouth, although the exposure was low. The findings warrant further attention to the effects of TRI especially on the central nervous system at the concentration lower than, e.g., 50 ppm.

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Experimental Human Exposure to Trichloroethylene

Cited by 105 publications

References 10 publications

Breath concentration as an index of the health risk from benzene. Studies on the accumulation and clearance of inhaled benzene.

Breath concentration as an index of the health risk from benzene. Studies on the accumulation and clearance of inhaled benzene.

Statistical analysis of Clewell et al. PBPK model of trichloroethylene kinetics.

Increased subjective symptom prevalence among workers exposed to trichloroethylene at sub-OEL levels.

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