Inflammatory and cardiometabolic risk on obesity: role of environmental xenoestrogens.

CONTEXT: Some chemicals used in consumer products or manufacturing (eg, plastics, pesticides) have estrogenic activities; these xenoestrogens (XEs) may affect immune responses and have recently emerged as a new risk factors for obesity and cardiovascular disease. However, the extent and impact on health of chronic exposure of the general population to XEs are still unknown. OBJECTIVE: The objective of the study was to investigate the levels of XEs in plasma and adipose tissue (AT) depots in a sample of pre- and postmenopausal obese women undergoing bariatric surgery and their cardiometabolic impact in an obese state. DESIGN AND PARTICIPANTS: We evaluated XE levels in plasma and visceral and subcutaneous AT samples of Portuguese obese (body mass index ≥ 35 kg/m(2)) women undergoing bariatric surgery. Association with metabolic parameters and 10-year cardiovascular disease risk was assessed, according to menopausal status (73 pre- and 48 postmenopausal). Levels of XEs were determined by gas chromatography with electron-capture detection. Anthropometric and biochemical data were collected prior to surgery. Adipocyte size was determined on tissue sections obtained during surgery. RESULTS: Our data show that XEs are pervasive in this obese population. Distribution of individual and concentration of total XEs differed between plasma, visceral AT, and subcutaneous AT, and the pattern of accumulation was different between pre- and postmenopausal women. Significant associations between XE levels and metabolic and inflammatory parameters were found. In premenopausal women, XEs in plasma seem to be a predictor of 10-year cardiovascular disease risk. CONCLUSIONS: Our findings point toward a different distribution of XE between plasma and AT in pre- and postmenopausal women, and reveal the association between XEs on the development of metabolic abnormalities in obese premenopausal women.

Pharmacological characterization of the discriminative stimulus of inhaled 1,1,1-trichloroethane.

The present study examined the involvement of the GABAA, N-methyl-D-aspartate (NMDA), nicotinic acetylcholine, and mu-opioid receptor systems in the transduction of the discriminative stimulus effects of the abused inhalant 1,1,1-trichloroethane (TCE). Sixteen B6SJLF1/J mice were trained to discriminate 10 min of exposure to 12,000-ppm inhaled TCE vapor from air. Substitution and antagonism tests and TCE blood concentration analysis were subsequently conducted. TCE blood concentrations decreased rapidly after cessation of exposure, falling by 66% within 5 min. TCE vapor concentration-dependently substituted for the 12,000-ppm training stimulus. The volatile anesthetic halothane concentration-dependently and fully substituted for TCE. The benzodiazepine midazolam partially substituted for TCE, producing a maximum of 68% TCE-lever selection. The benzodiazepine antagonist flumazenil attenuated midazolam substitution for TCE, but not the discriminative stimulus effects of TCE itself. The noncompetitive NDMA receptor antagonists phencyclidine and dizocilpine failed to substitute for TCE. Nicotine and the central nicotinic receptor antagonist mecamylamine also failed to produce any TCE-lever selection, nor did they antagonize the discriminative stimulus of TCE. The mu-opioid receptor agonist morphine did not substitute for TCE. The opioid antagonist naltrexone failed to antagonize the discriminative stimulus of TCE. Overall, the present results, combined with previous studies, suggest that the discriminative stimulus effects of TCE are mediated primarily by positive GABAA receptor modulatory effects though a mechanism distinct from the benzodiazepine binding site.

Discriminative stimulus effects of inhaled 1,1,1-trichloroethane in mice: comparison to other hydrocarbon vapors and volatile anesthetics.

RATIONALE: Because the toxicity of many inhalants precludes evaluation in humans, drug discrimination, an animal model of subjective effects, can be used to gain insights on their poorly understood abuse-related effects. OBJECTIVES: The purpose of the present study was to train a prototypic inhalant that has known abuse liability, 1,1,1-trichloroethane (TCE), as a discriminative stimulus in mice, and compare it to other classes of inhalants. MATERIALS AND METHODS: Eight B6SJLF1/J mice were trained to discriminate 10 min of exposure to 12,000 ppm inhaled TCE vapor from air and seven mice were trained to discriminate 4,000 ppm TCE from air. Tests were then conducted to characterize the discriminative stimulus of TCE and to compare it to representative aromatic and chlorinated hydrocarbon vapors, volatile halogenated anesthetics as well as an odorant compound. RESULTS: Only the 12,000 ppm TCE versus the air discrimination group exhibited sufficient discrimination accuracy for substitution testing. TCE vapor concentration- and exposure time-dependently substituted for the 12,000 ppm TCE vapor training stimulus. Full substitution was produced by trichloroethylene, toluene, enflurane, and sevoflurane. Varying degrees of partial substitution were produced by the other volatile test compounds. The odorant, 2-butanol, did not produce any substitution for TCE. CONCLUSIONS: The discriminative stimulus effects of TCE are shared fully or partially by chlorinated and aromatic hydrocarbons as well as by halogenated volatile anesthetics. However, these compounds can be differentiated from TCE both quantitatively and qualitatively. It appears that the degree of similarity is not solely a function of chemical classification but may also be dependent upon the neurochemical effects of the individual compounds.

Ethanol-induced increase in the metabolic clearance of 1,1,1-trichloroethane in human volunteers.

This study evaluated the effect of moderate doses of ethanol over a short period of time on the toxicokinetics of an organic solvent, 1,1,1-trichloroethane. A group of 10 moderate drinkers were recruited and exposed via inhalation for 2 h to a low concentration of 1,1,1-trichloroethane (175 ppm) on two separate occasions. Subjects were administered ethanol (0.35 g/kg body weight) on each of the 7 days preceding one of the exposures. Blood and urine samples were collected during and following each exposure, with blood analyzed for 1,1,1-trichloroethane and urine analyzed for the metabolites of 1,1,1-trichloroethane: trichloroethanol and trichloroacetic acid. Prior ethanol consumption resulted in a significant increase in apparent metabolic clearance of 1,1,1-trichloroethane (mean increase = 25.4%). The results of this study demonstrate that ethanol consumption over time can affect the rate at which an organic solvent is cleared through metabolism in humans. For chemicals with toxic metabolic products, this inductive effect of ethanol consumption on the rate of biotransformation could be potentially harmful to exposed individuals. Metabolic clearance of compounds with high hepatic extraction may not be affected by enzyme induction as it is likely that these compounds are essentially completely metabolized while passing through the liver.

Evaluation of dynamic headspace with gas chromatography/mass spectrometry for the determination of 1,1,1-trichloroethane, trichloroethanol, and trichloroacetic acid in biological samples.

A sensitive and reproducible method is described for the analysis of trichloroacetic acid in urine and 1,1,1-trichloroethane in blood using dynamic headspace GC/MS. Samples were analyzed using the soil module of a modified purge and trap autosampler to facilitate the use of disposable purging vessels. Coefficients of variation were below 3.5% for both analytes, and response was linear in the range of 0.01-7.0 microg/ml for trichloroacetic acid and 0.9 ng/ml-2.2 microg/ml for 1,1,1-trichloroethane. Attempts at using dynamic headspace for the analysis of trichloroethanol in urine were unsuccessful.

Residuals of beta-hexachlorocyclohexane, dichlorodiphenyltrichloroethane, and hexachlorobenzene in serum, and relations with consumption of dietary components in rural residents in Japan.

To estimate levels of organochlorine residuals in the Japanese population and the contribution of dietary factors to these levels, we determined serum levels of beta-hexachlorocyclohexane (beta-HCH), hexachlorobenzene (HCB), p,p'-dichlorodiphenyldichloroethane (p,p'-DDD), 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (p,p'-DDE) and p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT) in 41 volunteers (14 men and 27 women) in a rural area of Northern Japan. These organochlorine levels were measured using gas-chromatography mass-spectrometry. By a self-administered dietary history questionnaire, the usual dietary intake was estimated. Their median levels (range) were as follows: beta-HCH, 0.50 (0.05-1.50); HCB, 0.20 (0.02-0.70); and total DDT (p,p'-DDE + p,p'-DDT), 5.0 (0.9-31.0) ng/ml serum. Levels of p,p'-DDD were detected in only seven subjects (0.05-0.6 ng/ml serum). The beta-HCH levels were increased with rice and milk intakes, but the least squares means were not simply increased according to the quartile of the intakes. Concerning HCB, fish intake showed a borderline significant correlation (0.20, P = 0.052). In terms of total DDT, intakes of meat, fish, vegetable and milk showed a positive relationship, although none of them provided statistically significant results. No other statistically significant relation between any organochlorines and any food intakes examined was observed in this study. The present study suggests that organochlorine compounds are transported into the human body via foods in the Japanese population. Their effects on health should thus be investigated and monitored.

The importance of measured end-points in demonstrating the occurrence of interactions: a case study with methylchloroform and m-xylene.

Mixed exposures may result in significant changes in one biomarker of exposure without altering another biomarker, and this may have unknown significance in terms of exposure assessment and overall toxicity of the mixture. Results from a previous investigation showed that human exposure to methylchloroform (MC, 400 ppm) and m-xylene (XYL, 200 ppm) during 4 h did not result in any significant effect on blood concentrations of these solvents, suggesting the absence of interaction between MC and XYL. Those results were adequately described by conducting a physiologically-based toxicokinetic (PBTK) modeling of the MC-XYL interaction in humans; however, the model suggested that urinary excretion of MC metabolites would be reduced as a result of combined exposure, whereas that of XYL metabolites would not be modified. An experimental verification of this model prediction was then undertaken with rats. In this study, Sprague-Dawley rats (n, 5) were exposed during 4 h to MC (400 ppm) or XYL (200 ppm), alone or as a mixture. Results showed that combined exposure did not affect the blood concentration of MC whereas that of XYL was increased throughout the 2-h blood collection period following exposure. The excretion of MC metabolites during a period of 48 h following the onset of exposure, i.e., trichloroethanol (TCE: -71%) and trichloroacetic acid (TCA: -73%), were significantly reduced. Methylhippuric acid (MHA) was not affected by co-exposure to MC as expected from the PBTK model forecasts. These results exemplify the use of a priori PBPK modeling for designing interaction studies and choosing appropriate/sensitive end-points for demonstrating the occurrence of potential interactions.

Regional brain dosimetry of trichloroethane in mice and rats following inhalation exposures.

While certain neuroactive volatile organic compounds (VOCs) have been reported to have an uneven distribution in various anatomically distinctive brain regions, this has not yet been reported for the short-chain aliphatic halogenated hydrocarbons. Therefore, the uptake and regional brain distribution of 1, 1, 1-trichloroethane (TRI) in mice and rats following inhalation exposure were examined. Male Sprague-Dawley rats and CD-1 mice were exposed to TRI at either 3500 or 5000 ppm for 10, 30, 60, or 120 min. Seven brain regions from rats and three from mice were sampled, and TRI concentrations in the blood and brain tissues were determined by headspace gas chromatography. In both species, the medulla oblongata was found to have the highest TRI concentrations, while cortex (in both species) and hippocampus (only sampled in rats) contained the lowest TRI concentrations. Substantial differences were also observed between the two species, as the mice exhibited higher capacity to accumulate TRI in the blood as well as in the brain regions. It appears that lipid content is a main factor influencing the differential disposition of TRI among the brains regions. Physiological differences in the respiratory systems of the two species and the physiochemical properties of the chemical favoring diffusion toward lipid-rich compartments could also have been expected to account for the patterns of regional distribution and species differences.

Schedule-controlled operant behavior of rats during 1,1,1-trichloroethane inhalation: relationship to blood and brain solvent concentrations.

The central nervous system is the principal target of 1,1,1-trichloroethane (TRI), and several studies of this volatile solvent have demonstrated effects on learned animal behaviors. There have been few attempts, however, to quantitatively relate such effects to blood or target organ (brain) solvent concentrations. Therefore, Sprague-Dawley rats trained to lever-press for evaporated milk on a variable interval 30-s reinforcement schedule were placed in an operant test cage and exposed to clean air for 20 min, followed by a single concentration of TRI vapor (500-5000 ppm) for 100 min. Additional rats were exposed to equivalent TRI concentrations for 10, 20, 40, 60, 80, or 100 min to determine blood and brain concentration vs. time profiles. Inhalation of 1000 ppm slightly increased operant response rates, whereas 2000, 3500, and 5000 ppm decreased operant response rates in a concentration- and time-dependent manner. Accumulation of TRI in blood and brain was rapid and concentration dependent, with the brain concentration roughly twice that of blood. Plots of blood and brain TRI concentrations against operant performance showed responding in excess of control rates at low concentrations, and decreasing response rates as concentrations increased. Linear regression analyses indicated that blood and brain concentrations, as well as measures of time integrals of internal dose, were strongly correlated with operant performance. Neurobehavioral toxicity in laboratory animals, as measured by changes in operant performance, can therefore be quantitatively related to internal measures of TRI exposure to enhance its predictive value for human risk assessment.

Concentration in blood and organs of dogs after high dose 1,1,1-trichloroethane inhalation.

Dogs were exposed to 1% (v/v) (10,000 ppm) vapor of 1,1,1-Trichloroethane (1,1,1-TCE) by inhalation for 3 min repeated four times at 4 hr intervals under continuous anesthesia. Changes in the 1,1,1-TCE concentration in blood with time, as well as distribution of 1,1,1-TCE in the organs and tissues (lungs, liver, kidneys, heart, brain, and fat around the kidneys and on the abdominal wall) upon completion of the four exposures were studied. Concentrations of 1,1,1-TCE in blood showed the highest level immediately after exposure, and fairly decreased in about 30 min after exposure. The half life of 1,1,1-TCE in blood was 4-12 min after exposure. Upon completion of the exposures (3 min inhalations repeated four times), 1,1,1-TCE concentrations per gram wet weight of each organ ranged from 0.1 to 0.5 microgram/g in the lungs, liver, kidneys, heart and brain. On the other hand, the 1,1,1-TCE concentration in fat ranged from 16.9 to 54.6 micrograms/g, greatly exceeding those in other organs.

Acute effects of 1,1,1-trichloroethane inhalation on the human central nervous system.

The object of this study was to examine the immediate nervous effects of variable 1,1,1-trichloroethane (TCE) exposure combined with physical exercise. The effects on the quantitative electroencephalography (EEG), visual evoked potentials (VEP) and body sway were analyzed. Nine male volunteers were exposed to either a stable or a fluctuating exposure pattern with the same time-weighted average concentration of 200 ppm (8.1 mumol/l). In both cases, the subjects engaged in physical exercise during the exposures. Exercise alone induced an increase in the dominant alpha frequency in the EEG and, after an initial drop, an increase in the alpha percentage with a concomitant decrease in theta, whereas delta and beta bands remained unaffected. By contrast, exposure to TCI and exercise did not affect the alpha, theta or delta activities but induced changes in beta during the morning recordings at peak exposure to TCE. The body sway tended to decrease slightly during the fluctuating TCE exposure, and the later peaks in VEPs showed slight prolongations. Overall, no deleterious effects of exposure were noted.

Effect of various exposure scenarios on the biological monitoring of organic solvents in alveolar air. II. 1,1,1-Trichloroethane and trichloroethylene.

The purpose of the present study was to investigate the influence of different exposure scenarios on the elimination of trichloroethylene (TRI) and 1,1,1-trichloroethane (1,1,1-TRI) in alveolar air and other biological fluids in human volunteers. In addition, it was sought to establish an interactive process between experimental data gathering and simulation modeling in an attempt to predict the influence of the different scenarios of exposure to TRI and 1,1,1-TRI on their respective biological monitoring indices and thus to establish the flexibility and validity of simulation models. Two adult male and two adult female Caucasian volunteers were exposed by inhalation, in a dynamic controlled exposure chamber, to various concentrations of TRI (12.5-25 ppm) or 1,1,1-TRI (87.5-175 ppm) in order to establish the influence of exposure concentration, duration of exposure, variation of concentration within day, and work load on biological exposure indices. The concentrations of unchanged solvents in end-exhaled air and in blood as well as the urinary excretion of trichloroethanol (TCE) and trichloroacetic acid (TCA) were determined. The results show that doubling the exposure concentration for both solvents led to a proportional increase in the concentrations of unchanged solvents in alveolar air and blood at the end of a 7-h exposure period; this proportionality was still observable in 1,1,1-TRI expired air samples 16 h after the end of the third exposure day. In the case of urinary excretion of TCE and TCA, the proportionality between excretion and exposure concentration was not as good. It was once again observed that the slow excretion of both metabolites leads to progressive cumulation and that their urinary determination is subject to considerable interindividual variations. After adjustment (lowering) of the exposure concentration to account for a prolongation of the duration of exposure (from 8 to 12 h) it was observed that the concentrations of TRI or 1,1,1-TRI towards the end of both exposure periods are more a reflection of the actual exposure concentration than of the exposure duration. Despite important interindividual variations, these adjusted and nonadjusted exposures led to almost identical average total urinary excretion over 24 h) of TCE and TCA after exposure to 1,1,1-TRI, as was also the case for TCE but not for TCA after exposure to TRI. Induced within-day variations in the exposure concentration led to corresponding but not proportional changes in alveolar air concentrations for both solvents. After exposure to peak concentrations there was a lag period before alveolar air concentrations returned to prepeak levels. At the end of repeated 10-min periods of physical exercise at 50 W, alveolar air concentrations of TRI were increased by 50% while those of 1,1,1-TRI increased by only 12%. After optimization of the physiologically based toxicokinetic model parameters with experimental data collected during the first exposure scenario, results pertaining to the three other scenarios were adequately simulated by the optimized models. Overall, the results of the present study suggest that alveolar air solvent concentration is a reliable index of exposure to both TRI and 1,1,1-TRI under various experimental exposure scenarios. These results also suggest that urinary excretion of TCE and TCA must be interpreted with caution when assessing exposure to either solvents. For exposure situations likely to be encountered in the workplace, physiologically based toxicokinetic modeling appears to be a useful tool both for developing strategies of biological monitoring of exposure to volatile organic solvents and for predicting alveolar air concentrations under a given set of exposure conditions.

Inter-individual variability in blood/air partitioning of volatile organic compounds and correlation with blood chemistry.

In vitro blood/air partition coefficients (KB/A) for acetone, 1,1,1-trichloroethane, toluene, and styrene were measured in blood samples from 73 human subjects and correlated with blood chemistry parameters (hematocrit, total cholesterol, serum triglycerides, serum albumin, total plasma proteins, Na+, K+, Cl-, and HCO3-). Statistically significant inter-individual variation existed in KB/A between some subjects. Substitution of group or generic in vitro KB/A values for values determined in some individuals could introduce errors of up to 50%. However, most subjects could be well represented by group averages (mean +/- SD; acetone, 301 +/- 22; 1,1,1-trichloroethane, 6.0 +/- 0.8; toluene, 19 +/- 3; styrene, 62 +/- 10). The KB/A values for acetone, 1,1,1-trichloroethane and toluene were normally distributed. The data for styrene appeared to deviate from a normal distribution and may have been bimodal. The KB/A values for the two structurally related compounds, toluene and styrene, were strongly correlated within individuals, while the KB/A values for compounds with less structural similarity, such as acetone and styrene, were poorly correlated. At most, 15% of the variation in KB/A among individuals could be explained by variation in the measured blood chemistry parameters. When the entire sample group was considered, blood chemistry parameters were not significantly correlated with KB/A for any compound. The KB/A of 1,1,1-trichloroethane was significantly correlated with the concentration of cholesterol and triglycerides in females. Sex was a significant grouping variable for the correlation of albumin concentration with the KB/A of styrene. Age was not a significant correlation variable. Blood chemistry parameters which previously have been correlated with KB/A in small sample groups do not appear to be significantly correlated in our larger sample group.

Exposure of rats to high concentrations of 1,1,1-trichloroethane and its effects on brain lipid and fatty acid composition.

Exposure of rats to 1,1,1-trichloroethane (TRI) (1200 p.p.m.) for 30 days resulted in changes in the fatty acid pattern of the brain ethanolamine phosphoglyceride. A decrease was observed in stearic acid (18:0) and arachidonic acid (20:4), while the 22-carbon (n-3) fatty acids were increased. These changes in the fatty acid pattern were similar to that observed previously in the rat for another solvent, perchloroethylene, at a lower exposure concentration (320 p.p.m). Both these solvents are little metabolised and it seems that a common mechanism exists whereby these solvents alter the fatty acid pattern of brain phospholipid upon exposure. The relatively low uptake of TRI makes a high exposure level (1200 p.p.m.) necessary to attain a blood concentration high enough for the changes to appear.

Percutaneous absorption of 3 organic solvents in the guinea pig (V). Effect of "accelerants".

The influence of "accelerants" on the percutaneous absorption of 3 organic solvents (butanol, toluene, 1,1,1-trichloroethane) was investigated in the guinea pig. DMSO in binary and ternary mixtures with various concentrations, the result of adding 0.1 M C18 fatty acids, and of pretreatment with DMSO and olive oil, were studied. Addition of DMSO (binary solutions) resulted in increased or decreased absorption of the solvents related to their water solubility. There was reduced absorption of toluene and trichloroethane in binary mixtures with DMSO, while DMSO in binary mixture with butanol gave a marked increase, with concentrations of 50 and 75%. Pretreatment with DMSO resulted in a decrease in the absorption of toluene and a marked increase in the absorption of butanol. The same tendency was seen when skin was pretreated with olive oil under occlusion. The results indicate that the effect of DMSO is related to the water solubility of the penetrant.

Developmental toxicity of 1,1,1-trichloroethane in CD rats.

1,1,1-Trichloroethane (TCEN), a major industrial and household solvent, was evaluated for pre- and postnatal developmental effects in Sprague-Dawley rats. This study was designed to assess the repeatability of a report (S.C. Dapson, D.E. Hutcheon, and D. Lehr, Teratology 29, 25A, 1984) that indicated that 10 ppm TCEN in drinking water caused cardiac malformations in developing rats. In the present study, TCEN (97% pure) was administered in the drinking water at target concentrations of 3, 10, and 30 ppm, using 0.05% Tween 80 as an emulsifying agent. Two control groups, one receiving deionized/filtered water and the other receiving a vehicle control solution containing 0.05% Tween 80 and 0.9 ppm 1,4-dioxane, a stabilizing agent found in the bulk chemical, were also included. Male and female breeders (more than 30 per group) were exposed to the control solutions or test compound for 14 consecutive days prior to cohabitation and for up to 13 days during the cohabitation phase. Sperm-positive females (24-29 per group) continued to be exposed to these formulations during pregnancy and lactation to Postnatal Day (PND) 21. Parental animals exhibited a slight aversion to the 30-ppm drinking water during the premating exposure. No significant effect on reproductive competence of the parental animals or postnatal growth and development of the offspring to PND 21 was noted. A slight increase in mortality from implantation to PND 1, possibly due to high mortality in one litter, was observed in the 30-ppm dose group. There was no indication of an increase in the incidence of cardiac or other malformations in PND 21 pups. In summary, TCEN administered at 3, 10, and 30 ppm in the drinking water had no significant effect on the morphological development of CD rats.

Variability in biological monitoring of organic solvent exposure. II. Application of a population physiological model.

A physiological population model is used to study the variability associated with the biological monitoring of solvent exposure. The model consists of a combination of a physiological compartmental model and statistical simulation technique. Variable components considered are: exposure concentration, physical workload, body build, liver function, and renal function. The model is applied to six solvents: trichloroethylene, tetrachloroethylene, methylchloroform, benzene, toluene, and styrene. Biological indicators and air monitoring are compared as predictors of exposure, both external and internal (uptake, brain concentration, reactive metabolite formation). It appears that the choice of the best indicator depends on the type of exposure which is to be predicted. The effects of the various factors, environmental, physiological, or metabolic, are quantified and discussed. It is shown that fluctuation in exposure plays a large part in the final variability of biological indicator results. Further improvements and applications of this population model are considered.

Diagnosis and treatment of acute poisoning with volatile substances.

1. The acute toxicity of many volatile compounds is similar, being more related to physical properties than to chemical structure. 2. Volatile substance abusers experiences euphoria and disinhibition but this may be followed by nausea and vomiting, dizziness, coughing and increased salivation; cardiac arrhythmias, convulsions, coma and death occur in severe cases. 3. Laboratory analysis of blood and urine samples collected up to 24 h post-exposure may be helpful if the diagnosis of volatile substance abuse is in doubt. 4. There is only a weak correlation between blood toluene and 1,1,1-trichloroethane concentrations and the clinical features of toxicity, possibly because of rapid initial tissue distribution and elimination. 5. Recovery normally occurs quickly once exposure has ceased but support for respiratory, renal or hepatic failure may be needed as well as treatment for cardiac arrhythmias. Therapy with intravenous acetylcysteine should be considered in cases of acute carbon tetrachloride poisoning.

Behavioral changes during exposure to 1,1,1-trichloroethane: time-course and relationship to blood solvent levels.

We report the results of an exposure chamber study in which volunteers were exposed to 0, 950 mg.m-3 (175 ppm) and 1,990 mg.m-3 (350 ppm) of 1,1,1-trichloroethane for 3.5 hours. The time-course of the behavioral changes and the relationship to blood concentrations of 1,1,1-trichloroethane were investigated. A pattern of performance deficits consistent with earlier work was found for some of the tests of psychomotor performance. The time-course of these appeared to be rapid, occurring in some cases within 20 minutes of exposure. For those tasks shown to be sensitive to 1,1,1-trichloroethane exposure, the development of performance changes followed the time-course of blood solvent levels. Two behavioral tests not previously used in this type of work were also employed. One was concerned with the distractability of attention and concentration (the Stroop test), and the other was concerned with analysing grammatical statements (the syntactic reasoning test). Different effects were found. In the Stroop test, enhanced performance was observed following exposure; however, the syntactic reasoning test was found to be resistant to solvent effects. Measures of short-term subjective well-being were not affected by exposure. It is suggested that the observations of time-course effects in performance and their relationship to change in blood solvent levels have implications for psychological test selection and for study designs for examining field exposure.

Metabolites of chlorinated solvents in blood and urine of subjects exposed at environmental level.

After a two-level selection, 141 blood donors living in Milan, Italy, were analyzed for their content of plasma and urinary trichloroacetic acid (TCA) and trichloroethanol (TCE). Environmental levels of exposure to trichloroethylene (TRI) and tetrachloroethylene (PER) through drinking water and air were also measured. The plasma TCA levels were in the range of previously found concentrations. Relationships among plasma and urinary metabolites were found and discussed.