Abstract  The objective of this study was to compare the toxicokinetics of inhaled 1,2,4-trimethylbenzene (1,2,4-TMB) in man after exposure to white spirit with that observed after exposure to 1,2,4-TMB alone. TMBs occur mainly in petroleum products and the TMBs or their metabolites have been suggested as suitable biomarkers of exposure to white spirit and other distillation products. The toxicokinetics were studied in 9 male, healthy volunteers exposed to solvent vapours in an exposure chamber for 2 h during a work load of 50 W. The subjects were exposed to 11 mg/m3 of 1,2,4-TMB on two occasions; during exposure to 1,2,4-TMB vapour alone and during exposure to 300 mg/m3 of white spirit. The 1,2,4-TMB isomer was analyzed in blood and exhaled air by gas chromatography. In addition, a major urinary metabolite of 1,2,4-TMB, 3,4-dimethylhippuric acid (3,4-DMHA), was analyzed by high performance liquid chromatography. Further the occurrence of acute effects was studied by means of a questionnaire. Irritation and central nervous system symptoms were recorded by ratings on a 100-mm visual analogue scale. Blood levels of 1,2,4-TMB and excretion rates of 3,4-DMHA in urine were markedly elevated both during and after exposure to white spirit as compared to exposure to TMB alone. Thus, it appears that components in white spirit inhibit the metabolic elimination of 1,2,4-TMB. This should be considered in biological exposure monitoring as well as in risk assessment. No irritation or central nervous system effects were reported at these conditions.

Abstract  To evaluate the neurobehavioral effects of hydrocarbon solvents and to establish a working model for extrapolating animal test data to humans, studies were conducted which involved inhalation exposure of rats and humans to white spirit (WS). The specific objectives of these studies were to evaluate the behavioral effects of exposure to WS in rats and humans and to determine relationships between internal levels of exposure and behavioral effects. In both animals and volunteers, methods for assessment of similar functional effects were used to enable interspecies comparisons. A battery of tests including standardized observational measures, spontaneous motor activity assessments and learned visual discrimination performance was utilized in rat studies to evaluate acute central nervous system (CNS) depression. Groups of rats were exposed to WS at target concentrations of 0, 600, 2400 or 4800mg/m(3), 8h/day for 3 consecutive days. Blood and brain concentrations of two WS constituents; 1,2,4-trimethylbenzene (TMB) and n-decane (NDEC), were used as biomarkers of internal exposure. In a volunteer study, 12 healthy male subjects were exposed for 4h to either 57 or 570mg/m(3) WS in two test sessions spaced 7 days apart, and neurobehavioral effects were measured using a computerized neurobehavioral test battery. Blood samples were taken at the end of the exposure period to measure internal concentrations of TMB and NDEC. Results of the behavioral tests in rats indicated WS-induced changes particularly in performance and learned behavior. In humans, some subtle performance deficits were observed, particularly in attention. The behavioral effects were related to concentrations of the WS components in the central nervous system. These studies demonstrated a qualitative similarity in response between rats and humans, adding support to the view that the rodent tests can be used to predict levels of response in humans and to assist in setting occupational exposure levels for hydrocarbon solvents.

Abstract  Subjective symptoms and exposure to organic compounds were recorded in road repair and construction workers. Abnormal fatigue, reduced appetite, laryngeal/pharyngeal irritation, and eye irritation were recorded more often in such workers handling asphalt than in a corresponding reference group without asphalt exposure. Mean daily exposure to volatile compounds was only occasionally above 1 ppm. Mean exposure to asphalt fume was 0.358 mg/m3. There was no correlation between symptoms and total amount of volatile compounds, but a significant positive correlation was demonstrated between symptoms and some substances. The highest correlation was found for 1, 2, 4 trimethyl benzene. Symptoms increased with increasing asphalt temperature and with increasing concentrations of asphalt fumes. Amine addition did not increase the sum of symptoms, but soft asphalt seems to result in fewer symptoms than the harder types. Symptoms were not related to external factors like weather, traffic density, or specific working operations. As preventive measures, asphalt temperature should be kept below 150 degrees C, fume concentrations below 0.40 mg/m3, and if possible, the use of harder asphalt types which also require high temperatures should be avoided.

Abstract  In a painter's workshop, where 27 painters and 10 auxiliaries are employed, industrial hygiene and medical tests were performed in view to solve the question as to a relationship existing between the hydrocarbon solvents of high boiling point used in this workshop and the observed health damages. The results of these tests have shown that the painters have been working for several years mainly with a solvent composed of trimethylbenzene. The concentration of this solvent in the air varied between 10 and 60 ppm. Besides a survey of the general work conditions and of the sickness absenteism, the workers were submitted to a thorough medical examination. The latter revealed for the 27 painters a remarkably high percentage of subjective nervous complaints, bronchitis with asthma, anaemic hyperchromic blood picture, and coagulation troubles. These pathological states had to be put on account of the exposure to trimethylbenzene.

Abstract  Some clinical and laboratory studies indicate that industrial solvents such as toluene, styrene, xylene, trichloroethylene and carbon disulfide or their mixtures may affect the inner ear, although the mechanism of this process is still not well understood. The aim of this investigation was to assess the incidence of hearing and vestibular disorders (using modem audiological and vestibular tests) in 61 workers exposed to a mixture of organic solvents at the production of paints and varnishes; the control group included 40 age-matched non-exposed subjects. Environmental and biological monitoring revealed that the most significant exposure can be attributed to the following mixture constituents: ethylbenzene, xylene and trimethylbenzene isomers such as pseudocumene, mesitylene and hemimellitene. Electronystagmographic examinations showed the symptoms of vestibular dysfunction, as well as the decreased duration, amplitude and slow phase angular velocity of induced nystagmus in 47.5% of the subjects exposed versus 5% of controls. This was accompanied by sensorineural high frequency hearing loss, identified by means of pure tone audiometry in 42% of those exposed versus 5% controls, and reduced amplitudes of transiently evoked and distortion-product otoacoustic emissions. The findings closely correspond with the rate of the total exposure to the solvent mixture. A possible mechanism responsible for ototoxicity of solvents is discussed

Abstract  OBJECTIVES: To study mortality and prevalence of neuropsychological symptoms among a cohort of painters known to have been heavily exposed to organic solvents. METHODS: A mortality study of 1292 male painters who had worked in a dockyard in Scotland for > or = 1 year between 1950 and 1992 comprised a nested cross sectional study of 953 surviving painters from the cohort and 953 male non-painters randomly selected from the local population and a case-control study of those with high symptom scores. Mortality, symptoms, and risks associated with painting, adjusting for age, education, smoking, alcohol, and personality were measured. RESULTS: The proportional mortality ratio for all cancers was not increased significantly (110 (95% confidence interval (95% CI) 84 to 143), except for a possible excess of deaths from ischaemic heart disease (132, 105 to 164). Standardised mortality ratios were not significantly increased. Among the 260 surviving painters and 539 community controls who responded to the questionnaire there was a significant excess of symptoms among painters; adjusted relative risk (RR) increased significantly with increasing symptom score. These RRs suggested an exposure-response relation; for a high score (12-22) for all symptoms RR was 2.27 (1.20 to 4.30) for 1-4 years of exposure, 2.42 (1.18 to 4.95) for 5-9 years, 2.89 (1.42 to 5.88) for 10-14 years, and 3.41 (1.82 to 6.36) for 15-41 years, compared with controls. In multivariate analyses, painting exposure, and aging were associated with high symptom scores and there was again an increased risk relative to time worked as a painter. CONCLUSION: This study supports the hypothesis that heavy and prolonged exposure to paint solvents leads to neuropsychological ill health.

Abstract  The Ontario Ministry of the Environment (MOE) has identified the need to develop and/or update air quality standards for priority contaminants. The Ministry’s Standards Plan, which was released in October, 1996 and revised in November, 1999, identified candidate substances for which current air standards will be reviewed. Once all consultations have been completed, all substances will be incorporated into the Regulation as standards (as opposed to guidelines). 1,2,4-Trimethylbenzene (1,2,4-TMB) was identified as a high priority compound for review based on its pattern of use in Ontario and recent toxicological information that has been published. This document provides a review of scientific and technical information relevant to the setting of Ambient Air Quality Criteria (AAQC) and half-hour Point of Impingement (POI) standards for 1,2,4-TMB and other trimethylbenzene isomers.