Neurobehavioral toxicity of long-term exposure to tetrachloroethylene

doi:10.1016/0892-0362(89)90041-X

Neurotoxicology and Teratology

Volume 11, Issue 6, November–December 1989, Pages 579-583

https://doi.org/10.1016/0892-0362(89)90041-X Get rights and content

Abstract

One hundred and one employees of dry cleaning shops exposed to tetrachloroethylene (time weighted average 205 mg/m³) and 84 employees of departmental stores and hotels were compared from the results of a psychological examination. Age, gender, the daily consumption of alcohol and the intellectual level were taken into consideration analysing the effects of tetrachloroethylene. Perceptual speed, digit reproduction as a memory test, the digit symbol test as a substitution task and variables of a choice reaction test as well as a cancellation test differed significantly between the controls on one hand, and the groups of low and high exposure on the other. But, the differences between the exposure groups were not significant. There was no effect of alcohol on the exposure-related group differences. By means of discriminant analyses the diagnostic effectiveness of the biochemical, neurological and psychological methods were compared to classify the subjects into exposure groups. The highest rate of correct classifications was performed by the multidisciplinary combination of approaches.

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Cited by (37)

Prenatal and early childhood exposure to tetrachloroethylene (PCE) and non-medical use of prescription drugs: A retrospective cohort study in Cape Cod, MA
2021, Environmental Research
Citation Excerpt :
Additionally, there is evidence of associations between PCE and other neurotoxic outcomes such as decreased cognition, ocular effects, and impairment of neuropsychological function (e.g. reaction time) (ATSDR, 2019; Bale et al., 2011; Guyton et al., 2014; White et al., 1995), which have been observed in both animal experiments and epidemiological studies in occupational and community settings. Studies following chronic occupational exposure to PCE have suggested that exposure influences the functioning of the front lobes (mediating executive functioning and reasoning) as well as the limbic system (mediating mood and memory) (Altmann et al., 1995; Echeverria et al., 1995; Seeber, 1989). Thus, a potential mechanism in which PCE may lead to use of drugs could be related due to neurological changes that impair impulse control and adversely influence judgement and mood as observed in occupational studies (Altmann et al, 1992, 1995; Janulewicz et al., 2012).
Between 1968 and 1983, public drinking water supplies of Cape Cod, Massachusetts were contaminated with the chlorinated solvent tetrachloroethylene (PCE). We previously found an affinity for risk-taking behaviors, including the use of illicit drugs, following prenatal and early childhood exposure to PCE. Using newly collected data, we investigated the risk of non-medical use of prescription drugs (NMUPD) following prenatal and early childhood PCE exposure.
Participants were identified from a retrospective cohort study ("Cape Cod Health Study”) via cross-matching birth certificates and water system data. The original self-administered questionnaire gathered data on demographics, work and medical history, and alcohol and illicit drug use from 618 individuals (363 exposed and 255 unexposed). The follow-up survey added questions on non-medical use of prescription pain relievers, tranquilizers, stimulants and sedatives. A validated leaching and transport model was used to estimate exposure to PCE exposure in drinking water.
There was a wide distribution of cumulative prenatal and early childhood PCE exposure levels (range: 0.04 g–3722.2 g). PCE exposed subjects had a 1.92-fold increase in risk of any non-medical use of prescription drugs [Adjusted RR: 1.92, (95% CI: 1.31, 2.83)]. Furthermore, the association followed a dose-response relationship where the risk of NMUPD was higher for those exposed to PCE levels greater than or equal the median level versus those exposed to levels less than the median [Adjusted RR: 2.05 (95% CI: 1.34, 3.15) vs. 1.83 (95% CI: 1.20, 2.79) (p-value for trend < 0.01)]. Additionally, we found moderate increases in risk by level of non-medical use (any non-medical use, non-medical use of 1 or more categories of prescription drugs, or 2+ categories) as well as by category of drug for pain relivers, stimulants and tranquilizers.
We found that prenatal and early childhood exposure to PCE was associated with a moderate increase in the risk of NMUPD. Exposed subjects had dose-related increased risks of NMUPD of pain relievers, tranquilizers, and stimulants. This study has a number of limitations and is the first to report this association. Additional longitudinal studies of populations exposed to PCE during early life should be conducted to examine its long-term neurotoxic effects.
Combination effect of ultrasound and shake as a mechanical action for textile cleaning
2015, Ultrasonics Sonochemistry
Citation Excerpt :
Commercial dry-cleaning with organic detergent solvents has been utilized for delicate garments. However, the solvents cannot remove water-soluble contaminants sufficiently as well as have human toxicity and environmental impacts [1,2]. Moreover, many dry cleaning accidents have been recently reported, especially for the textiles coated and laminated with other materials.
The ultrasonic cleaning of artificially soiled fabrics with and without shake was carried out in an aqueous anionic surfactant solution. The polyester, cotton and polyester/cotton (65/35) fabrics were soiled with oleic acid or carbon black as a model soil, and cleaned together with their original fabrics with applying ultrasound for 5 min. The detergency and the soil redeposition were determined from the change in the Kubelka–Munk function of the soiled and original fabric surfaces due to the cleaning. For any fabric, the removal of oleic acid and carbon black from the soiled fabric and their redeposition onto the original fabric increased with increasing electric power consumption of ultrasound. When ultrasound and shake were applied at the same time, the detergency further increased for any electric power consumption. The maximum detergency obtained with combination of ultrasound 340 W and shake 160 spm was compared with detergency obtained with Wascator, a horizontal axis drum type washer. It was found that the ultrasound/shake combination cleaning enabled efficient removal of both soils from any fabric and the detergency of the polyester fabrics was comparable to that with Wascator. The mechanical action during the washing was evaluated by two mechanical action test pieces commercially available, which indicated that the ultrasound/shake combination cleaning provided gentle mechanical action to the fabric in comparison with the drum type washer. The SEM observations showed the damage of the fabric and fiber surfaces was negligibly small after the ultrasound/shake combination washing.
Clinical impact assessment of chronic exposure to tetrachloroethylene in a population of 50 dry-cleaning workers
2011, Archives des Maladies Professionnelles et de l'Environnement
Évaluation du retentissement clinique de l’exposition chronique au perchloroéthylène dans une population de salariés de pressing. Évaluation métrologique et biométrologique de cette exposition et validation de l’hypothèse d’une exposition respiratoire au-delà des valeurs indicatives en lien avec des pics d’exposition répétés. Recherche des facteurs professionnels influençant cette exposition.
Après définition du protocole, inclusion des salariés des pressings de deux services de santé au travail (Brest et Quimper). Étude exposés/non exposés pour l’évaluation de la symptomatologie clinique avec appariement sur l’âge, le sexe, le tabac. Évaluation de l’exposition professionnelle par prélèvement atmosphérique sur badge Gabie sur une journée et dosage sanguin du perchloroéthylène en fin de semaine. Recueil des données d’activité lors de la semaine d’étude (avril 2009).
Cinquante salariés et 95 témoins ont été inclus. Les symptômes neurologiques sont prépondérants chez les salariés, il n’y a pas de signes de somnolence (Epworth < 8 pour 84 %) et la présence d’un syndrome prénarcotique (SPN) n’est retrouvée que pour 10 % des salariés. Pas de différence significative entre population exposée et non exposée sur la présence de signes cliniques, la somnolence et le SPN. La moyenne des taux atmosphériques en perchloroéthylène est de 7 ppm (0,22–33) et tous sont inférieurs à la valeur moyenne d’exposition et la médiane au niveau sanguin de 73,6 μg/l (11,8–544) avec aucun résultat supérieur à la valeur guide française. Cinquante-six pour cent des salariés ont une concentration sanguine en perchloroéthylène supérieure aux valeurs recommandées actuellement pour les femmes enceintes et 67 % en référence aux nouvelles valeurs de l’ANSES. Une corrélation faiblement significative entre les valeurs des taux atmosphériques et les activités de raclage des boues et changement de filtres est notée.
Des axes d’amélioration de la prévention collective et individuelle sur les opérations exposantes (raclage de boues, nettoyage de filtre, test au perchloroéthylène) ressortent de l’analyse. La répétition des pics de perchloroéthylène n’entraîne pas d’exposition supérieure aux valeurs recommandées. La clinique est indiquée dans le suivi des expositions subaiguës mais doit être associée à la biométrologie pour les expositions chroniques. Une attention particulière doit être prise pour les femmes en âge de procréer avec information sur les risques. Le faible effectif, de notre étude, nous permet d’émettre ces hypothèses sans toutefois pouvoir les affirmer.
To evaluate the clinical impact of chronic exposure to perchloroethylene in a population of dry cleaning workers. Atmospheric and biometrological assessment of this exposure and validation of the hypothesis that repeated exposure peaks lead to a respiratory exposure beyond the guideline values. Search for occupational factors influencing exposure.
After defining the protocol, inclusion of the employees of dry cleaning shopsof two Occupational Health Services (Brest and Quimper). Study of the exposed/unexposed population to evaluate the clinical symptoms with matching on age, sex, tobacco smoking. Evaluation of occupational exposure by air sampling, during 1 day, by means of the Gabie badge and determination of perchloroethylene blood concentration at the end of the week. Data collection activity during the study week (April 2009).
Fifty workers and 95 controls were included. Neurological symptoms are prominent among employees, there are no signs of sleepiness (Epworth < 8 to 84%) and the presence of a prenarcotic syndrome (PNS) is found for only 10% of the employees. No significant differences between exposed and unexposed populations are noted concerning clinical symptoms, drowsiness and PNS. The average atmospheric perchloroethylene concentration is 7 ppm (0.22–33) and all concentrations are below the French average threshold limit value of exposure, and the median blood level of perchloroethylene is 73.6 μg/l (11.8 to 544) with no result above the French guideline value. Fifty-six percent of the employees have a blood concentration of perchloroethylene greater than that presently recommended for pregnant women and 67% when referring to the new ANSES values of. A significant correlation between the values 56% of atmospheric levels and activities of sludge scraping and filter change is noted.
For collective and individual prevention, improvements on technical operations (sludge scraping, filter cleaning, perchloroethylene test) emerge from the analysis. The repetition of perchloroethylene exposure peaks does not cause excess exposure than recommended. The clinical examination can be used in the follow-up of subacute exposures but must be combined with biometrics for chronic exposures. Particular attention should be paid to women of childbearing age with information concerning the risks. The small size of our study allows us to make these assumptions without being however able to assert them.
Development and evaluation of a harmonized physiologically based pharmacokinetic (PBPK) model for perchloroethylene toxicokinetics in mice, rats, and humans
2011, Toxicology and Applied Pharmacology
Citation Excerpt :
A recently updated occupational cohort study reported a new finding of increased incidence of end-stage renal disease among dry cleaning workers, further supporting a role for perc in kidney toxicity (Calvert et al., 2010). However, the strongest and most consistent epidemiologic evidence remains that for neurotoxic effects (Altmann et al., 1995; Echeverria et al., 1995; Ferroni et al., 1992; Schreiber et al., 2002; Seeber, 1989). A simplified metabolism scheme for perc is shown in Fig. 1.
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.
Perchloroethylene exposure and biological surveillance
2010, Archives des Maladies Professionnelles et de l'Environnement
Cytotoxicity evaluation after coexposure to perchloroethylene and selected peroxidant drugs in rat hepatocytes
2004, Toxicology in Vitro
There is evidence of hepatotoxic effects caused by Perchloroethylene (PCE), presumably due to reactive metabolic intermediates; lipid peroxidation is under study as a potential mechanism of toxicity. We aimed to verify if PCE levels comparable to those reached in the blood of exposed subjects can cause cell damage and lipid peroxidation. The association of PCE with lipid peroxidation inducing drugs (cyclosporine A, valproic acid and amiodarone) was also tested on rat isolated hepatocytes. AST and LDH release, MTT test and lipid peroxidation assay showed that PCE determines dose-dependent effects on rat isolated hepatocytes. The toxic potential resulting from our data would be valproic acid<cyclosporine A<amiodarone. While valproic acid and cyclosporine caused a mild toxicity, the effects of amiodarone were more severe; in particular, the association of PCE with amiodarone showed a clear additive effect. The role of lipid peroxidation in the liver toxicity exerted by the tested compounds was confirmed by our data, and resulted relevant after treatment of cells with amiodarone and PCE. Extrapolating these results to human, we can suggest that a subject professionally exposed to PCE, who chronically assumes a lipid peroxidation inducing drug like amiodarone, may be potentially exposed to a higher risk of liver toxicity.

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^☆: The investigations were carried out at the Central Institute of Occupational Medicine, Berlin (GDR), the former workplace of the author. The exposure measurements were performed by the Inspectorate of Occupational Hygiene at the Local Council of Berlin (GDR). I would like to thank Prof. Gerhard Winneke (Medical Institute of Environmental Hygiene, Düsseldorf, FRG) for helpful comments in drawing up the paper.

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Neurobehavioral epidemiologyNeurobehavioral toxicity of long-term exposure to tetrachloroethylene☆

Abstract

Chronische Tetrachlorethylenexposition unter Berücksichtigung der Ethanolaufnahme—Eine epidemiologische Querschnitt-Studie

Use of behavioral performance tests in the assessment of solvent toxicity

Scand. J. Work Environ. Health

Querschnittsstudie zur Frage der Gesundheitsschädigung durch chronische Perchloräthylen-Exposition

Human exposure to tetrachlorethylene inhalation and skin contact

Environ. Health Perspect.

Behavioral test battery of toxicopsychological studies

Does solvent poisoning exists?

Health surveillance of workers exposed to tetrachloroethylene in dry-cleaning shops

Int. Arch. Occup. Environ. Health

Aufnahme, Metabolisierung und Ausscheidung von Tetrachlorethylen und Beeinflussung durch gleichzeitige Aufnahme von Ethanol beim Menschen

Neurobehavioral epidemiology
Neurobehavioral toxicity of long-term exposure to tetrachloroethylene☆