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Tetrachloroethylene (Perc) (Final, 2012)

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Data/Software
Data/ Software

PERC risk assessment model

Authors: Chiu, WA; Ginsberg, GL (2011) [MCSim Code]. Washington, DC: U.S. Environmental Protection Agency. [Database] HERO ID: 784005

Abstract: Use GNU MCSim Monte Carlo Simulation Software version 5.x to run attached code.

Data/Software
Data/ Software

Final PBPK model simulation files

Author: U.S. EPA (2011) HERO ID: 787065

[Less] "SimulationFilesDirectory.rtf" file in the zip archive provides a description of each model simulation . . . [More] "SimulationFilesDirectory.rtf" file in the zip archive provides a description of each model simulation file

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Development and evaluation of a harmonized physiologically based pharmacokinetic (PBPK) model for perchloroethylene toxicokinetics in mice, rats, and humans

Authors: Chiu, WA; Ginsberg, GL (2011) Toxicology and Applied Pharmacology 253:203-234. HERO ID: 713689

[Less] This article reports on the development of a “harmonized” PBPK model for the toxicokinetics of perchloroethylene . . . [More] This article reports on the development of a “harmonized” PBPK model for the toxicokinetics of perchloroethylene (tetrachloroethylene or perc) in mice, rats, and humans that includes both oxidation and glutathione (GSH) conjugation of perc, the internal kinetics of the oxidative metabolite trichloroacetic acid (TCA), and the urinary excretion kinetics of the GSH conjugation metabolites N-Acetylated trichlorovinyl cysteine and dichloroacetic acid. The model utilizes a wider range of in vitro and in vivo data than any previous analysis alone, with in vitro data used for initial, or “baseline,” parameter estimates, and in vivo datasets separated into those used for “calibration” and those used for “evaluation.” Parameter calibration utilizes a limited Bayesian analysis involving flat priors and making inferences only using posterior modes obtained via Markov chain Monte Carlo (MCMC). As expected, the major route of elimination of absorbed perc is predicted to be exhalation as parent compound, with metabolism accounting for less than 20% of intake except in the case of mice exposed orally, in which metabolism is predicted to be slightly over 50% at lower exposures. In all three species, the concentration of perc in blood, the extent of perc oxidation, and the amount of TCA production is well-estimated, with residual uncertainties of ~ 2-fold. However, the resulting range of estimates for the amount of GSH conjugation is quite wide in humans (~ 3000-fold) and mice (~ 60-fold). While even high-end estimates of GSH conjugation in mice are lower than estimates of oxidation, in humans the estimated rates range from much lower to much higher than rates for perc oxidation. It is unclear to what extent this range reflects uncertainty, variability, or a combination. Importantly, by separating total perc metabolism into separate oxidative and conjugative pathways, an approach also recommended in a recent National Research Council review, this analysis reconciles the disparity between those previously published PBPK models that concluded low perc metabolism in humans and those that predicted high perc metabolism in humans. In essence, both conclusions are consistent with the data if augmented with some additional qualifications: in humans, oxidative metabolism is low, while GSH conjugation metabolism may be high or low, with uncertainty and/or interindividual variability spanning three orders of magnitude. More direct data on the internal kinetics of perc GSH conjugation, such as trichlorovinyl glutathione or tricholorvinyl cysteine in blood and/or tissues, would be needed to better characterize the uncertainty and variability in GSH conjugation in humans.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Exposure to tetrachloroethylene in dry cleaning shops in the Nordic countries

Authors: Lynge, E; Tinnerberg, H; Rylander, L; Romundstad, P; Johansen, K; Lindbohm, ML; Heikkilä, P; Westberg, H; Clausen, LB; Piombino, A; Thorsted, BL (2011) Annals of Occupational Hygiene 55:387-396. HERO ID: 716622

[Less] Tetrachloroethylene is the dominant solvent used in dry cleaning worldwide and many workers are potentially . . . [More] Tetrachloroethylene is the dominant solvent used in dry cleaning worldwide and many workers are potentially exposed. We report here on results of 1296 measurements of tetrachloroethylene undertaken in Nordic dry cleaning shops 1947-2001.

We searched documents and files in the Nordic institutes of occupational health for air measurements of tetrachloroethylene. Repeated measurements from the same facility during a short time interval were registered only once using the time-weighted average. We registered also changes over time in occupational exposure limits (OELs) to tetrachloroethylene.

Only scattered measurements were available from the early years, and the exposure level seemed fairly stable up until the mid 1970s. The median exposure level was 20 p.p.m. in 1976 and decreased to 3 p.p.m. in 2000. Exposure levels in the four Nordic countries followed similar trends. In the late 1960s, the OELs varied between the Nordic countries from 30 to 100 p.p.m. Sweden was first to lower the limit, but limits gradually converged over time. At present, Denmark, Finland, and Sweden use 10 p.p.m., while Norway uses 6 p.p.m. Over time, the average observed exposure level was lower than the OEL in all countries, but in Denmark and Sweden, up to one-third of measured exposures exceeded the OEL. Overall, the stationary measurements for maintenance work showed 36 p.p.m., while the personal measurements showed 7.5 p.p.m. for dry cleaners and 6.25 p.p.m. for shop assistants.

The Nordic data illustrate that it is possible over time to control chemical exposures even in an industry consisting of many small and scattered work places.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Trichloroacetic acid: Updated estimates of its bioavailability and its contribution to trichloroethylene-induced mouse hepatomegaly

Author: Chiu, WA (2011) Toxicology 285:114-125. HERO ID: 729640

[Less] Trichloroacetic acid (TCA) is a common drinking water disinfection byproduct that produces a spectrum . . . [More] Trichloroacetic acid (TCA) is a common drinking water disinfection byproduct that produces a spectrum of liver effects, including hepatomegaly and liver tumors, in mice. It is also an oxidative metabolite of trichloroethylene (TCE), a solvent used in degreasing with widespread environmental exposure, which also produces hepatomegaly and liver tumors in mice. Physiologically based pharmacokinetic (PBPK) modeling of TCE and TCA can be used to quantitatively compare the dose-responses for hepatomegaly for these two chemicals on the basis of internal TCA dose, and thereby test the hypothesis that TCA could fully explain TCE-induced hepatomegaly. Previously, using a PBPK model calibrated using kinetic data from i.v. and gavage dosing of TCA and from TCA produced from TCE, it was concluded that TCA accounted for only about one-fifth of the degree of hepatomegaly produced by TCE. However, recently available data suggest a non-linear change in internal TCA dose attributed to a dose-dependent fractional absorption of TCA administered in drinking water, the primary route of exposure of TCA both environmentally and in experimental toxicity studies. Therefore, in the present reanalysis, the PBPK modeling of TCA was updated using these data and the comparison between TCA- and TCE-induced hepatomegaly was revisited using updated internal dose predictions. With respect to updated PBPK modeling results, incorporating less than complete absorption of TCA administered in drinking water substantially improves the PBPK model fit to the newly available data, based on goodness-of-fit comparison. However, inter-experimental variability is high, with nearly complete absorption estimated for some studies. With respect to the comparison of TCA and TCA-induced hepatomegaly, this reanalysis predicts that TCA can account for roughly one-third to one-half of the effect observed with TCE - greater than previously reported, but still inconsistent with TCA being the sole active moiety for this effect. However, given uncertainty as to the precise degree of contribution of TCA and due to high inter-experimental variability in estimated fractional absorption, a more precise quantitative estimate of the relative contribution of TCA may obtained through an appropriate experiment in mice simultaneously measuring TCA kinetics and TCE- and TCA-induced hepatomegaly.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Carcinogenicity of chemicals in industrial and consumer products, food contaminants and flavourings, and water chlorination byproducts

Authors: Grosse, Y; Baan, R; Secretan-Lauby, B; El Ghissassi, F; Bouvard, V; Benbrahim-Tallaa, L; Guha, N; Islami, F; Galichet, L; Straif, K (2011) Lancet Oncology 12:328-329. HERO ID: 730457


The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Visual contrast sensitivity in children exposed to tetrachloroethylene

Authors: Storm, JE; Mazor, KA; Aldous, KM; Blount, BC; Brodie, SE; Serle, JB (2011) Archives of Environmental and Occupational Health 66:166-177. HERO ID: 735838

[Less] This study examined relationships between indoor air, breath, and blood tetrachloroethylene (perc) levels . . . [More] This study examined relationships between indoor air, breath, and blood tetrachloroethylene (perc) levels and visual contrast sensitivity (VCS) among adult and child residents of buildings with or without a colocated dry cleaner using perc. Decreasing trends in proportions of adults or children with maximum VCS scores indicated decreased VCS at a single spatial frequency (12 cycles per degree [cpd]) among children residing in buildings with colocated dry cleaners when indoor air perc level averaged 336 μg/m3; breath perc level averaged 159.5 μg/m3; and blood perc level averaged 0.51 μg/L. Adjusted logistic regression indicated that increases in indoor air, breath, and blood perc levels among all child participants significantly increased the odds for decreased VCS at 12 cpd. Adult VCS was not significantly decreased by increasing indoor air, breath, or blood perc level. These results suggest that elevated residential perc exposures may alter children's VCS, a possible subclinical central nervous system effect.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Occupation and risk of lymphoma: A multicentre prospective cohort study (EPIC) - Erratum

Authors: Neasham, D; Sifi, A; Nielsen, KR; Overvad, K; Raaschou-Nielsen, O; Tjønneland, A; Barricarte, A; González, CA; Navarro, C; Rodriguez Suarez, L; Travis, RC; Key, T; Linseisen, J; Kaaks, R; Crosignani, P; Berrino, F; Rosso, S; Mattiello, A; Vermeulen, RC; Bueno-de-Mesquita, HB; Berglund, G; Manjer, J; Zackrisson, S; Hallmans, G; Malmer, B; Bingham, S; Khaw, KT; Bergmann, MM; Boeing, H; Trichopoulou, A; Masala, G; Tumino, R; Lund, E; Slimani, N; Ferrari, P; Boffetta, P; Vineis, P; Riboli, E (2011) Occupational and Environmental Medicine 68:550. [Erratum] HERO ID: 3449167


Technical Report
Technical Report

Toxicological review of Tetrachloroethylene (Perchloroethylene) (CASRN 127-18-4) in support of summary information on the Integrated Risk Information System (IRIS)

Author: U.S. EPA (2011) HERO ID: 737542


The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Risk of lung cancer associated with quantitative beryllium exposure metrics within an occupational cohort

Authors: Schubauer-Berigan, MK; Deddens, JA; Couch, JR; Petersen, MR (2011) Occupational and Environmental Medicine 68:354-360. HERO ID: 667892

[Less] Objectives Beryllium has been identified as a human carcinogen on the basis of animal and epidemiological . . . [More] Objectives Beryllium has been identified as a human carcinogen on the basis of animal and epidemiological studies. The authors recently reported updated associations between lung cancer and beryllium exposure in a large, pooled occupational cohort. The authors conducted the present study to evaluate the shape of exposure-response associations between different exposure metrics and lung cancer in this cohort, considering potential confounders (race, plant, professional and short-term work status, and exposure to other lung carcinogens). Methods The authors conducted Cox proportional hazards regression analyses of lung cancer risk with cumulative, mean and maximum 'daily weighted average' (DWA) exposure among 5436 workers, using age-based risk sets. Different exposure-response curves were fitted to the exposure metrics, including categorical, power, restricted cubic spline and piecewise log-linear fits. Results The authors found significant positive associations between lung cancer and mean (p<0.0001) and maximum (p<0.0001) exposure, adjusting for age, birth cohort and plant, and for cumulative (p=0.0017) beryllium exposure, adjusting for these factors plus short-term work status and exposure to asbestos. The best-fitting models were generally categorical or piecewise log-linear, with the steepest increase in lung cancer risk between 0 and 10 μg/m(3) for both mean and maximum DWA exposure and between 0 and 200 μg/m(3)-days for cumulative DWA exposure. The estimated mean DWA beryllium exposure associated with 10(-3) excess lifetime risk based on the piecewise log-linear model is 0.033 μg/m(3). Conclusion This study provides evidence that lung cancer risk is elevated at levels near the current US Occupational Safety and Health Administration beryllium exposure limit of 2.0 μg/m(3) DWA for workers.