|IDENTIFICATION AND USE: o-Cresol forms crystals in liquid becoming dark with age and exposure to light and air. It has been used in explosive, petroleum, photographic, paint, and agricultural industries, as an intermediate for the production of pesticides, epoxy resins, dyes and pharmaceuticals, but also as a component of disinfectants and cleaning agents.
HUMAN EXPOSURE AND TOXICITY: o-Cresol is a respiratory irritant in humans. Eight of 10 subjects exposed to "brief exposure" to a concentrated aerosol of 6 mg/cu m o-Cresol complained of dryness, nasal constriction, and throat irritation. Dose-dependent SCE increases were not observed in cultured human fibroblasts at concentrations up to 8 mM. There was a small but significant increase in SCE frequency compared to control at 8 mM.
ANIMAL STUDIES: In an acute dermal toxicity study, technical grade o-cresol caused severe skin damage on at least 2/6 shaved, female, albino rabbits within 4 hours of application of 890 mg/kg . o-Cresol can cause severe local irritation and corrosion following dermal and ocular exposure. Eye irritation can be severe and include corneal opacity. All three cresols isomers are more toxic to mice than to rats when administered by gavage. o-Cresol is the most toxic, followed by p-cresol and then m-cresol. The effects are similar to, but less severe than, those following phenol exposure. Phenol, o- and p-cresol have about equal toxicity in cats while m-cresol is slightly less toxic. An assortment of respiratory effects, including inflammation and irritation of the upper respiratory tract, pulmonary edema, and hemorrhage and perivascular sclerosis in the lungs were seen in animals exposed to 9-50 mg/cu m of o-cresol 2-6 hours/day for 1 month or more. In mice exposed to a mixture of o-cresol aerosol and vapor 2 hr/day, 6 days/week for 1 month no mortality was recorded. Clinical signs of toxicity during the daily exposure periods were limited to signs of respiratory irritation at the start of the exposure, followed by a period of hypoactivity lasting until the end of the exposure. Microscopic examination revealed signs of irritation in the respiratory tract. Other lesions included degeneration of heart muscle, liver, kidney and nerve cells and glial elements of the central nervous system. A detailed oral neurotoxicity study of intermediate duration was performed on rats using all three cresol isomers. A host of clinical observations indicative of neurotoxicity (including hypoactivity, rapid labored respiration, excessive salivation, and tremors) was reported at doses of 50 mg/kg/day or higher for all three isomers. Convulsions were reported at 450 mg/kg/day or higher. o-Cresol appeared to lengthen the estrus cycle in treated female rats and mice. Developmental effects have been reported in animals given cresols, but only at maternally toxic doses. Maternal effects in rats dosed throughout gestation occurred at 450 mg/kg/day. At this dose o-cresol produced slight fetotoxicity, but had no effect on malformation incidence or gestation parameters. In rabbits dosed throughout gestation, maternal effects, such as audible respiration, ocular discharge, and hypoactivity, were seen following exposure to o-cresol at 50 mg/kg/day. At 100 mg/kg/day, o-cresol produced fetotoxicity, but no other effects at any dose. Chromosomal aberrations were induced in Chinese hamster (CHO) cells in both the presence and absence of S9 mix, following treatment with o-cresols. Mice were given a single dermal application of 9,10-dimethyl-1,2-benzanthracene (DMBA), a cancer initiator, followed by application of 20% solutions of o-cresol in benzene twice a week for 12 weeks. Promotion with o-cresol led to increases in the average number of skin papillomas per mouse and the percentage of exposed mice with at least one papilloma. Carcinomas were not observed following cresols exposure, although the observed papillomas have the potential to develop into carcinomas.
ECOTOXICITY STUDIES: Sarotherodon mossambicus (a teleost) was exposed to a sublethal concentration of o-cresol for 30 days and observed to show degenerative changes. LC50 value for 96 hr exposure of 23.5 mg/L. Growth studies have shown that o-cresols are moderately toxic to aquatic bacteria, cyanobacteria (blue-green algae) and protozoa. Growth inhibition thresholds were 33 mg/L for the bacterium Pseudomonas putida; 6.8 mg/L for the cyanobacterium Microcystis aeruginosa; 17 mg/L for the bacterivorous flagellate protozoan Entosiphon sulcatum and 132 mg/L for the saprozoic flagellate protozoan, Chilomonas paramecium.