Abstract  The interaction of tetrachloroethylene with hepatic microsomal cytochromes P-450 has been investigated using male Long-Evans rats. The spectral binding of tetrachloroethylene to cytochromes P-450 in hepatic microsomes from uninduced rats was characterized by a Ks of 0.4 mM. The Ks was not affected by phenobarbital induction, but was increased following pregnenolone-16α-carbonitrile induction. The KM of 1.1 mM, calculated for the conversion of tetrachloroethylene to total chlorinated metabolites by the hepatic microsomal cytochrome P-450 system, was decreased by phenobarbital induction and increased by pregnenolone-16α-carbonitrile induction. The maximum extents of binding (ΔAmax) and metabolism (Vmax) of tetrachloroethylene were increased by both phenobarbital and pregnenolone-16α-carbonitrile induction. Induction with β-naphthoflavone was without effect on any of the above parameters. The effects of the inducing agents on tetrachloroethylene-stimulated CO-inhibitable hepatic microsomal NADPH oxidation followed the same trend as their effects on Vmax for the metabolism of tetrachloroethylene, although in all cases the extent of NADPH oxidation was 5- to 25-fold greater than the extent of metabolite production. The inhibitors of cytochromes P-450, viz. metyrapone, SKF 525-A, and CO, inhibited the hepatic microsomal binding and metabolism of tetrachloroethylene. Free trichloroacetic acid was found to be the major metabolite of tetrachloroethylene from the hepatic microsomal cytochrome P-450 system. Neither 2.2,2-trichloroethanol nor chloral hydrate was produced in measurable amounts from tetrachloroethylene. A minor but significant metabolite of tetrachloroethylene by cytochrome P-450 was the trichloroacetyl moiety covalently bound to components of the hepatic microsomes. Incubation of tetrachloroethylene. an NADPH-generating system. EDTA and hepatic microsomes was without effect on the levels of microsomal cytochromes P-450, cytochrome b5, beme, and NADPH-cytochrome c reductase. It is concluded that hepatic microsomal cytochromes P-450 bind and metabolize tetrachloroethylene. The major product of this interaction is trichloroacetic acid, which is also the major urinary metabolite of tetrachloroethylene in vivo. The forms of cytochrome P-450 that bind and metabolize tetrachloroethylene include those induced by pregnenolone-16α-carbonitrile and by phenobarbital. Cytochrome P-448. which was induced in rat liver by β-naphthoflavone, does not appear to spectrally bind or metabolize tetrachloroethylene. The metabolism and toxicity of tetrachloroethylene are considered in relation to other chlorinated ethylenes.

Abstract  Control rabbits or those treated with 2,4-dichloro-6-phenylphenoxyethyldiethylamine-HBr (Lilly 18947), an inhibitor of microsomal mixed-function oxidases, were exposed to 5200 ppm tetrachloroethylene in an inhalation chamber under dynamic airflow conditions for 1 h. Even at this high concentratio, tetrachloroethylene was only weakly arrhythmogenic when animals were challenged with up to 3 μg/kg epinephrine i.v. Unlike trichloroethylene and methylchloroform, the arrhythmogenicity of tetrachloroethylene was not potentiated by treatment with Lilly 18947.

Abstract  British journal of industrial medicine e field[29]: Perchloroethylene

Abstract  There is considerable potential for worker exposure to tetrachloroethylene, both by skin contact and by inhalation, during its use in dry cleaning and degreasing operations. This paper reviews accounts of both accidental overexposures of workers and controlled exposures of human subjects by these two routes of exposure. Several reported cases of accidental overexposure to anesthetic doses of the chemical reveal that recovery was generally complete but prolonged, and accompanied by many days of measurable levels of the chemical in the patient's alveolar breath. Chronic overexposures of workmen have lessened since the general acceptance by the Western world of the recommended TLV of 100 ppm for 8 hr of daily exposure. Controlled inhalation studies with volunteer subjects at this level of exposure revealed no effects upon health but did indicate a slight decrement in performance on a coordination test. Additional behavioral and neurological tests revealed no interactive effects when alcohol or diazepam, two depressant drugs, were added singly to tetrachloroethylene exposures. Individual susceptibility to the vapor of this chemical, as evidenced by subjective complaints, was noted in approximately one of ten subjects. The authors conclude that the TLV concentration of 100 ppm in the workplace has a negligible margin of safety regarding unimpaired performance during repeated exposures which could be especially hazardous if the worker is physically active or is in a situation where skin absorption presents an added burden.

Abstract  A 6-week-old breast-fed infant had obstructive jaundice and hepatomegaly. When a dry-cleaning solvent, tetrachloroethylene, was detected in the mother's milk and blood, breast-feeding was discontinued. Rapid clinical and biochemical improvement followed. The child grew normally and had normal liver function during 2 years of follow-up.

Abstract  British journal of industrial medicine e field[29]: Perchloroethylene

Abstract  Abstract: dogs es references. e field[29]: Perchloroethylene

Abstract  The relatively high and almost constant absorption/min of trichloroethylene (TRI) is explained by the relatively high partition coefficient between blood and air (lambdab/g = 15) combined with the rapid metabolism (75 %). Tetrachloroethylene (PERC) has about the same lambdab/g as TRI, but the metabolism is insignificant (2 %); therefore, the amount taken up/min decreases in the course of exposure. The lambdab/g (5) for 1,1,1-trichloroethane (MC) is smaller, the metabolism is insignificant (3.5 %), therefore the capacity of the body to absorb MC is relatively small and in consequence the uptake/min decreases fast in the course of exposure. Due to the lower lambdab/g the excretion of MC after exposure is much faster than of PERC. As a result of the metabolism of TRI only a relatively small amount of TRI absorbed is excreted by the lungs after exposure.

Abstract  It is known from industrial experience and experimental studies that percutaneous absorption of concentrated liquid solvents may be considerable and even hazardous if large enough areas of skin are exposed for long periods of time. Percutaneous penetration of xylene, styrene, toluene, 1,1,1-trichloroethane and tetrachloroethylene vapors at ambient air concentrations of 600 ppm for 3.5 h was studied in a dynamic exposure chamber with a restricted number of human volunteers. Although the small number of exposed persons precluded conclusive quantitation of absorption and valid intercompound comparisons, aromatic solvents and tetrachloroethylene appear to penetrate skin much more readily than 1,1,1-trichloroethane. Skin penetrating properties of solvents seem, under the circumstances, to be associated primarily with lipid solubility. It was approximated that percutaneous exposure (total body surface) to 600 ppm of xylene vapor for 3.5 h corresponded to an equally long inhalation exposure of less than10 ppm. Similar percutaneous exposure to 1,1,1-trichloroethane corresponded to an inhalation exposure of only 0.6 ppm. Disease-affected skin may display altered permeability characteristics, and one volunteer with atopic dermatitis exhibited a more than three times larger absorption of xylene vapor when compared to subjects with normal skin. It may be concluded that in the work environment percutaneous absorption of solvent vapors from the surrounding air through undamaged skin is likely to be insignificant.

Abstract  Tetrachloroethylene (1,1,2,2-tetrachloroethene) is a widely used organic solvent capable of producing adverse renal, hepatic, and central nervous system effects. The cardiac effects of tetrachloroethylene, thus far unexplored, were studied in several species. To standardize the dosimetry, tetrachloroethylene was prepared for intravenous injection in solutions of Tween 80, which had no demonstrable cardiotoxicity. In rabbits under urethane and in cats and dogs under pentobarbital, tetrachloroethylene increased the vulnerability of the ventricles to epinephrine-induced extra-systoles, bigeminal rhythms, and tachycardia. The mean threshold doses of tetrachloroethylene were 10 mg/kg in rabbits, 24 mg/kg in cats, and 13 mg/kg in dogs. In rabbits this threshold dose for cardiac arrhythmias correspond to blood levels between 2.2 and 3.6 microgram/ml. Animals demonstrating a reflex bradycardia to vasopressor doses of epinephrine were relatively resistant to the arrhythmogenic action of tetrachloroethylene. Ventricular arrhythmias occurred in less than 30% of the animals after tetrachloroethylene alone. In cats higher doses of tetrachloroethylene (40 mg/kg) produced acute pulmonary edema. Tetrachloroethylene (30-40 mg/kg) decreased left intraventricular dP/dt (max) in dogs, without significantly increasing left intraventricular end-diastolic pressure, although there was a transient decrease in arterial blood pressure that accompanied the early phase of myocardial depression. These results are being used as the basis for studies of the chronic effects of tetrachloroethylene on cardiac performance.

Abstract  Case-referent studies were performed within two cohorts of women engaged in laundry or dry-cleaning work. The aim was to elucidate if tetrachloroethylene (perchloroethylene) exposure increased the risk of adverse pregnancy outcome (spontaneous abortion, perinatal death, congenital malformations or birth weight < 1,500 g). Pregnancies and outcomes were identified in national registers and exposure data were obtained from the women by postal questionnaires. Response rates were 75-88%. Conditional logistic regression analysis of the total material yielded an adjusted odds ratio for tetrachloroethylene exposure during the first trimester of 1.1 (95% confidence interval 0.6–2.0) when several potential confounding factors were accounted for. The total material included few highly exposed pregnancies and a limited number of cases of specific adverse outcomes. Consequently, the results do not invalidate the recommendation that tetrachloroethylene should be handled with caution by women in childbearing ages.

Abstract  Fischer 344 rats and B6C3F1 mice of both sexes were exposed to 400 ppm perchloroethylene (PER) by inhalation, 6 hr/day for 14, 21, or 28 days or to 200 ppm for 28 days. Increased numbers of peroxisomes were seen under the electron microscope and increased peroxisomal cyanide-insensitive palmitoyl CoA oxidation was measured (3.6-fold increase in males and 2.1-fold increase in females) in the livers of mice exposed to PER. Hepatic catalase was not increased. Peroxisome proliferation was not observed in rat liver or in the kidneys of either species. Trichloroacetic acid (TCA), a known carcinogen and hepatic peroxisome proliferating agent, was found to be a major metabolite of PER. Blood levels of this metabolite measured in mice and rats during and for 48 hr after a single 6-hr exposure to 400 ppm PER showed that peak blood levels in mice were 13 times higher than those seen in rats. Comparison of areas under the curves over the time course of the experiment showed that mice were exposed to 6.7 times more TCA than rats. The difference in metabolism of PER to TCA in mice and rats leads to the species difference in hepatic peroxisome proliferation which is believed to be the basis of the species difference in hepatocarcinogenicity. Peroxisome proliferation does not appear to play a role in the apparent carcinogenicity of PER in the rat kidney.

Abstract  The numbers of deaths by cause among 1,292 white male metal polishers and platers identified from obituary listings in the Journal of the Metal Polishers, Buffers, Platers, and Allied Workers International Union were compared to an expected distribution based on the white male population of Illinois and the U.S. The proportions of deaths due to cancers of the esophagus and the liver were high, particularly among those over 65 and those listed as metal polishers or platers on the death certificate. The PCMRs for these two tumors were also moderately elevated. Despite methodologic limitations, these findings, along with the known use in this industry of chromium and nickel, strong acid and alkaline solutions, and the solvents trichloroethylene and tetrachloroethylene, suggest that metal polishers and platers may be subject to exposures capable of inducing cancer.

Abstract  A case-referent study of occupational risk indicators of renal cell adenocarcinoma was conducted. Each incident case in Finland in 1977-1978 was matched with two population referents. Lifelong job histories were collected and translated into indicators of industry, occupation, and occupational exposures. The analyses of 338 sets of cases and referents revealed elevated risks for a history of employment in white-collar occupations; the printing industry; the chemical industry; the manufacturing of metal products; mail, telephone, and telegraph services; and iron and metalware work. A decreased risk was observed for male farmers. An elevated risk and an exposure-response relationship were found for gasoline exposure. The excess risk was highest at a latency period of approximately 30 years. The findings support the hypothesis that exposure to some constituent(s) of gasoline increases the incidence of renal adenocarcinoma in humans. Suggestions of elevated risks appeared for exposures to inorganic lead, cadmium, and nonchlorinated solvents.

Abstract  BACKGROUND: Paternal exposure to mutagenic agents has been suggested to affect pregnancy outcome adversely. METHODS: A nationwide data base of medically diagnosed spontaneous abortions and other pregnancies and national census data was used to evaluate the effects of men's occupational exposures on risk of spontaneous abortion in 99,186 pregnancies in Finland. Census data from the years 1975 and 1980 provided information about the occupation, industry, and socioeconomic status. A job-exposure classification was developed to classify women and their husbands according to possible occupational exposures on the basis of their occupational title and industry. RESULTS: In 10% of the pregnancies, the husband was exposed to one or more of the mutagens, and the rate of spontaneous abortion was unaffected (OR = 1.0). Of the 25 specific mutagenic exposures evaluated, paternal exposure to four (ethylene oxide, rubber chemicals, solvents used in refineries, and solvents used in the manufacturing of rubber products) was associated with an increased relative risk of spontaneous abortion. In addition, the risk of spontaneous abortion was higher among wives of rubber products workers than among unexposed men. CONCLUSIONS: Although there is some biological rationale for the findings of this study, these findings need to be confirmed by studies in which individual exposures can be measured directly.

Abstract  In recent years, there have been growing concerns that due to differences, both pharmacokinetic and pharmacodynamic, between children and adults, children could be at greater risk of adverse effects following chemical exposure. The specific goal of this study was to demonstrate an approach for using physiologically based pharmacokinetic (PBPK) modeling to compare inhalation dosimetry in the adult and the child of both males and females. Three categories of gases were considered: rapidly and irreversibly reactive in the respiratory tract (ozone), relatively water-soluble and nonreactive (isopropanol), and relatively water-insoluble and nonreactive (styrene, vinyl chloride, and perchloroethylene). The nonreactive chemicals were also selected because they are metabolized in the respiratory tract. The age-related changes observed for the estimated dose metrics were a function of the physiochemical properties of the inhaled vapor and their interactions in the body. Blood concentrations estimated for all vapors, either poorly metabolized (e.g., PERC), moderately metabolized (e.g., ST), or highly metabolized vapors (e.g., IPA and VC), varied less than a factor of two between infants and adults. These changes, moreover, were confined to the first year after birth, a relatively short window compared to the total lifespan of the individual. In contrast, circulating metabolite concentrations estimated in the blood, as well as amounts metabolized in the liver and lung, appeared to be a strong function of age, due to their dependence on the maturity of the pertinent metabolic enzyme systems.

Abstract  The hypothesis that long-term low-level exposure to perchloroethylene (PERC) may impair the dopaminergic control of prolactin (PRL) secretion and negatively affect neurobehavioral performance, was tested in a cross-sectional survey of dry-cleaners. Sixty female workers exposed to PERC in dry-cleaning shops and thirty controls recruited in a cleaning plant not using solvents were examined. PERC air concentration during four-hour random periods varied from 1 to 67 ppm (median 15 ppm). PERC blood levels ranged 12-864 mg/l (median 145 mg/l). A set of tests from a computer-based performance evaluation system was administered, including Finger Tapping with both dominant and non-dominant hands, Simple Reaction Times, Digit Symbol, and Shape Comparison in two different versions constructed to test Vigilance and the response to moderate stress, respectively. During the proliferative phase of the menstrual cycle, PERC-exposed workers showed increased serum PRL (12.1 +/- 6.7 ng/ml) as compared to their matched controls (7.4 +/- 3.1 ng/ml, p less than 0.001). Prolonged reaction times were also observed in all tests. However, neither the duration of exposure nor air and blood PERC concentrations were significantly correlated with performance. Nor were exposure variables associated with the increased PRL levels.

Abstract  BIOSIS COPYRIGHT: BIOL ABS. RRM CHILD ALDEHYDES KETONES HALOGENS HYDROCARBONS AROMATICS CENTRAL NERVOUS SYSTEM DAMAGE OCCUPATIONAL EXPOSURE PREGNANCY MENTAL RETARDATION GROWTH MATERNAL DRUG ABUSE MCCARTHY SCALES OF GENERAL ABILITIES

Abstract  BACKGROUND: Tetrachloroethylene, also known as perchloroethylene or