We present in this paper a review of the toxicological and environmental hazards, exposures and risks of tetrahydrofuran (THF; CASRN 109-99-9). THF is a polar solvent and monomer that is easily absorbed by all routes of exposure. The acute toxicity of THF is low to moderate by all routes. Irreversible corrosive damage to the eye can result from direct contact. However, THF is neither a skin irritant, nor sensitizer. Studies in vitro and in vivo have shown that THF is not mutagenic. Chronic studies have found benign tumors in the kidneys of male rats and in the livers of female mice. These findings have been examined, and although a mode of action is not known, the weight of evidence suggests that these tumors are likely not relevant to human health, but instead secondary to rodent-specific modes of action. THF produces transient sedative effects in rats at high concentrations but no significant neurobehavioral changes or neuropathology in sub-chronic studies. There were no specific effects reported on reproduction or developmental toxicity in rats or mice, with non-specific developmental toxicity observed only in the presence of significant maternal toxicity. The log K(ow) value for THF is less than 3, indicating a low potential for bioaccumulation. THF is inherently biodegradable, thus is not expected to be environmentally persistent. THF does not present an ecotoxicity hazard based on test results in fish, aquatic invertebrates and plants. Exposures to THF in the workplace, to consumers and via environmental releases were modeled and all found to fall below the derived toxicity thresholds.
The present studies indicate pronounced species-, sex-, and strain- related differences in the acute nephrotoxicity of hydroquinone (HQ) when administered by gavage to male and female Sprague-Dawley (SD) rats, Fischer 344 (F344) rats, and B6C3F1 mice. Following a single dose of 400 mg/kg, male and female F344 rats displayed pronounced enzymuria and glucosuria. In female F344 rats, urinary alkaline phosphatase and glucose were the most sensitive indicators of renal toxicity, reaching levels of, respectively, 157 times and 137 times control values within 24 h of dosing. HQ treatment of male F344 rats also resulted in significant enzymuria, although it was less marked than that seen in female F344 rats. Significant numbers of epithelial cells were also present in the urine from F344 rats at 200 (female) or 400 mg/kg (male and female). SD rats did not show evidence of elevated levels of urinary enzymes or increased blood urea nitrogen (BUN) after oral administration of HQ at a dose level of 400 mg/kg. Oral administration of HQ to male and female B6C3F1 mice at 350 mg/kg resulted in only slight but significant increases in BUN.
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