Effects on laboratory animals and in vitro systems. White spirit possesses low acute toxicity for mammals. Thus an LC50 for rats was not achieved with 8-h exposure to 8200 mg/m3 (1400 ppm). In a group of four cats, all were killed at 10 000 mg/m3 (vapour and aerosols). The general signs were irritation, loss of coordination, tremor and clonic spasms. No mortality was found after oral administration (gavage) of 5000 mg/kg to rats. In rabbits loss of appetite and hypoactivity followed a single dermal exposure of 2000-3000 mg/kg, and death occurred in 1 out of 16 exposed animals. In skin irritation tests white spirit was determined to be a slight to moderate irritant. In short- and long-term toxicity studies on white spirit, the central nervous system (CNS), respiratory system, liver and kidney were generally found to be the target of white spirit toxicity. Irritation of the respiratory tract has been observed following inhalation exposure, and histopathological signs from irritation have been observed in rats exposed nose-only to 4-h exposures for 4 days at 214 mg/m3. Guinea-pigs were the most sensitive of five species tested with long-term exposure. There was increased mortality following 90 days of continuous exposure to levels of 363 mg/m3 or more. During postmortem examinations pulmonary irritation was found. Rats exposed to 4800 mg/m3, 8 h daily, for 26 weeks exhibited reduced nerve conduction velocity in the tail axon. Neurobehavioural tests indicated only mild effects and only immediately after a daily exposure. Rats exposed to 2290 and 4580 mg/m3, 6 h daily, for 3 weeks or 6 months were found to develop increases in the levels of catecholamines and serotonin in the brain and reduced protein content in synaptosomes isolated from the animals. No effects were noted in neurobehavioural tests. Neurophysiological recordings have shown changes in sensory evoked potentials in the brain of rats measured 2 months after a 6-month period of exposure to either 2339 or 4679 mg/m3 (400 or 800 ppm) of dearomatized white spirit. Three weeks of exposure to this solvent also resulted in increased levels of reactive oxygen species in brain tissue from the rats. In several inhalation studies, male rats developed the so-called "alfa2-microglobulin nephropathy". Repeated dermal exposure of rabbits caused reduction in weight gain and liver toxicity at dose levels of 2000 mg/kg, given 3 times weekly for 4 weeks. There have been three developmental toxicity studies, all of which reported essentially negative findings. However, insufficient data are available for a comprehensive assessment. White spirit was not found to be genotoxic in assays using Salmonella typhimurium and Saccharomyces cerevisiae, a mouse lymphoma mutation assay, mouse and rat bone marrow cytogenic tests, and rodent (rat and mouse) dominant lethal tests. No carcinogenicity studies have been performed with experimental animals exposed to white spirit. Related heavier and lighter refinery distillation streams such as kerosene, straight-run and light straight-run naphtha have induced skin tumours in mice after 80 weeks of skin application. Effects on humans. The odour threshold of white spirit is quite low, and vapours can be detected at levels of 0.5-5 mg/m3. Tolerance of the odour may be developed. Eye irritation has been reported in connection with acute exposure down to a level of 600 mg/m3 (100 ppm). At higher levels respiratory irritation and more pronounced eye irritation occur. Acute CNS symptoms such as headache, "drunkenness", dizziness and fatigue have been reported in several cases of occupational exposure. Controlled 7-h exposure to levels of 600 mg/m3 or more resulted in impaired balance during walking and to an increased reaction time. Exposure to 4000 mg/m3 for 50 min resulted in impaired performance in tests for perceptual speed and short-term memory. One case of cyanosis, apnoea and cardiac arrest after excessive inhalation exposure during painting has been reported. Ingestion of white spirit has been reported to produce gastrointestinal irritation with pain, vomiting and diarrhoea. Lesions of the mucous membranes in the oesophagus and the gastrointestinal tract followed the oral exposure. Owing to its low viscosity and low surface tension, white spirit poses a risk of aspiration into the lungs following oral exposure. A few ml of solvent aspirated into the lungs are able to produce serious bronchopneumonia and 10-30 ml may be fatal. Prolonged dermal exposure to white spirit, e.g., resulting from wearing clothes that have been soaked or moistened by white spirit for hours, may produce irritation and dermatitis. Single cases of acute toxicity to the kidney, liver and bone marrow have been reported following exposure to white spirit at high levels. However, owing to lack of details and the sporadic nature of the reportings, the relevance of these findings is unclear. There have been few reports concerning the haematological or biochemical effects of white spirit. However, clinical studies reveal decreased erythrocyte, leukocyte and platelet counts, and increased mean corpuscular volume in exposed workers. Similar haematological changes have been observed in animal studies. There are no consistent serum biochemical changes; reduced aspartate aminotransferase and lactate dehydrogenase activity and elevated creatinine kinase activity have been observed. Numerous epidemiological studies have been performed involving painters with long-term exposure to white spirit. Increased incidence of complaints of memory impairment, fatigue, impaired concentration, irritability, dizziness, headache, anxiety and apathy have been demonstrated in several cross-sectional studies. Studies including neuropsychological tests have shown impaired ability in performing some of the tests. In some studies an overall reduction in cognitive functioning was noted to a degree that corresponded to a diagnosis of chronic toxic encephalopathy. In a few studies a dose-response relationship was established. This was the case in a comprehensive study in which painters predominantly exposed to white spirit were compared with non-exposed bricklayers. Painters with low solvent exposure were comparable to non-exposed bricklayers with regard to neuropsychological test results. However, the prevalence of impaired functioning increased with increasing exposure in the groups of painters with medium and high exposure. Similar complaints and neuropsychological test results, although more severe, were reported from clinical studies in which painters predominantly exposed to white spirit had been referred to occupational medical clinics for detailed examinations because of health complaints and suspected chronic toxic encephalopathy due to the long-term solvent exposure. In case-control studies, increased odds ratios for the award of disability pension because of mental disturbances were found for painters compared to other occupational groups not exposed to white spirit or other solvents. Several case-control studies have shown a high risk of glomerulonephritis among painters. Even though cross-sectional studies using early markers of nephropathy were inconclusive, they are consistent with the hypothesis that painters have an increased risk of glomerulonephritis and renal dysfunction. Several minor studies concerning reproductive effects in humans have been undertaken. In one of the most extensive studies, reproductive parameters were compared between members of a union for painters and members of a union for electricians. No firm conclusion in this or in the other studies could be drawn as no significant differences occurred. Nevertheless, there is a suggestion that parental exposure to solvents may have an untoward effect on the offspring. However, there is no adequately reported information directly related to white spirit. Few epidemiological studies of cancer in humans exposed solely to white spirit are available. Increased risks of respiratory, pancreatic and kidney cancer have been reported in three studies on dry cleaners where white spirit was the predominant cleaning solvent. For painters, an occupational group widely exposed to white spirit, evidence has been found of increased cancer risks, particularly in the lung and bladder. There was no increase in sister-chromatic exchange in a group of painters with long-term solvent exposure. However, there were some small increases in cytogenetic damage in a small number of humans exposed mainly to petroleum vapours. Effects on other organisms in the laboratory and field. Few studies on the toxicity of white spirit to organisms other than laboratory mammals have been reported. Reports of inhibitory effects on growth of the fungus Aspergillus niger have been made, although concentrations of the white spirit in the growth medium were difficult to assess. No effects were found on mycorrhizal fungi in a single study. Increased oxygen uptake by excised plant root tips has been reported; the significance of this finding is doubtful for actual exposure in the field. The few studies on the aquatic toxicity of white spirit and related hydrocarbon mixtures indicate moderate toxicity to freshwater and marine organisms. The toxicity is probably due to the dissolved fraction and leads to 96-h LC50 values of the order of 0.5 to 5.0 mg/litre. These results are likely to overestimate the effects of white spirit in the field, given its volatility and lowered bioavailability following sorption to soil/sediment. (Shortened).
