Identity, physical and chemical properties. Hydroquinone (1,4-benzenediol; C6H4(0H)2) is a white crystalline substance when pure, with a melting point of 173-174 degrees C. The specific gravity is 1.332 at 15 degrees C, and the vapour pressure is 2.4 x 10-3 Pa (1.8 x 10-5 mmHg) at 25 degrees C. It is highly soluble in water (70 g/litre at 25 degrees C) and the log n-octanol/water partition coefficient is 0.59. With respect to organic solvents, the solubility varies from 57% in ethanol to less than 0.1% in benzene. Hydroquinone is combustible when preheated. It is a reducing agent which is reversibly oxidized to its semiquinone and quinone. Environmental transport, distribution and transformation. Hydroquinone occurs in the environment as a result of manmade processes as well as in natural products from plants and animals. Due to its physicochemical properties, hydroquinone will be distributed mainly to the water compartment when released into the environment. It degrades both as a result of photochemical and biological processes; consequently, it does not persist in the environment. The BOD5/COD ratio, which is an indicator of biodegradability, has been reported to be 0.37 and 0.53 in two different studies. No bioaccumulation is observed. A bioconcentration factor (BCF) for Leusiscus idus was 40, (static test, 3 days). Effects on laboratory mammals, and in vitro systems. Oral LD50 values for several animal species range between 300 and 1300 mg/kg body weight. However, for the cat LD50 values range from 42 to 86 mg/kg body weight. Acute high-level exposure to hydroquinone causes severe effects on the central nervous system (CNS) including hyperexcitability, tremor, convulsions, coma and death. At sublethal doses these effects are reversible. The dermal LD50 value has been estimated to be 3800 mg/kg in rodents. Inhalation LC50 values are not available. A formulation containing 2% hydroquinone in a single-insult patch test in rabbits resulted in an irritation score of 1.22 (on a scale of 0 to 4). Daily topical applications for three weeks of 2 or 5% hydroquinone in an oil-water emulsion on the depilated skin of black guinea-pigs caused depigmentation, inflammatory changes and thickening of the epidermis. The depigmentation was more marked at higher concentrations, and female guinea-pigs were more sensitive than males. Sensitization tests in guinea-pigs have shown weak to strong reactions depending on the methods or vehicles used. The strongest reactions were obtained with the guinea-pig maximization test. A cross-sensitization of almost 100% between hydroquinone and p-methoxyphenol was also seen in guinea-pigs, but only restricted evidence of cross-reactions to p-phenylenediamine, sulfanilic acid and p-benzoquinone was obtained. A 6-week oral toxicity study in male F-344 rats resulted in nephropathy and renal cell proliferation. Thirteen-week oral gavage studies in F-344 rats and in B6C3F, mice resulted in nephrotoxicity in rats at 100 and 200 mg/kg, and tremors and convulsions in rats at 200 mg/kg; reduced body weight gain was seen in both rats and mice. Dosing at 400 mg/kg was lethal in rats. In mice dosed for 13 weeks at 400 mg/kg, tremors, convulsions and lesions in the gastric epithelium were reported. Thirteen-week hydroquinone exposure of Sprague Dawley rats resulted in decreased body weight gain and CNS signs at 200 mg/kg. CNS signs were also observed at a dose level of 64 mg/kg body weight but not at 20 mg/kg. Hydroquinone injected subcutaneously reduced fertility in male rats, and prolonged the estrus cycle in female rats. However, this was not found in oral studies (a dominant lethality study and a two-generation study). In a developmental study in rats, oral doses of 300 mg/kg body weight caused slight maternal toxicity and reduced fetal body weight. In rabbits, the no-observed-effect level (NOEL) for maternal toxicity was 25 mg/kg per day, and it was 75 mg/kg per day for developmental toxicity. In a twogeneration reproduction study in rats hydroquinone caused no reproductive effects at oral doses of up to 150 mg/kg body weight per day. The no-observed-adverse-effect level (NOAEL) for parental toxicity was determined to be 15 mg/kg per day, and for reproductive effects through two generations it was 150 mg/kg per day. Hydroquinone induces micronuclei in vivo and in vitro. Structural and numerical chromosome aberrations have been observed in vitro and after intraperitoneal administration in vivo. Furthermore, the induction of gene mutations, sister-chromatid exchange and DNA damage has been demonstrated in vitro. Hydroquinone caused chromosomal aberrations in male mouse germ cells at the same order of magnitude as in mouse bone marrow cells after intraperitoneal injection. Induction of germcell mutations could not be established in a dominant lethal test in male rats dosed orally. In a two-year study, oral administration of hydroquinone caused a dose-related incidence of renal tubular cell adenomas in male F-344/N rats. The incidence was statistically significant in the high-dose group. In the high-dose males, renal tubular cell hyperplasia was also found. In female rats a dose-related increased incidence of mononuclear cell leukaemia occurred. Female B6C3F, mice developed a significantly increased incidence of hepatocellular adenomas. In another study, hydroquinone (at a dietary level of 0.8%) produced a significantly increased incidence of epithelial hyperplasia of the renal papilla and a significant increase of renal tubular hyperplasia and adenomas in male rats. No increased incidence of mononuclear cell leukaemia in female rats was observed. In mice, the incidence of squamous cell hyperplasia of the forestomach epithelium was significantly increased in both sexes. In male mice, there was a significantly increased incidence of hepatocellular adenomas and also of renal tubular hyperplasia. A few renal cell adenomas were observed. In vivo (intraperitoneal injection) and in vitro studies in mice have demonstrated that hydroquinone has a cytotoxic effect by reducing the bone marrow and spleen cellularity and also an immunosuppressive potential by inhibiting the maturation of B-lymphocytes and the natural killer cell activity. Results also indicate that bone marrow macrophages may be the primary target for hydroquinone myelotoxicity. Myelotoxic effects were not observed in a long-term bioassay in rodents. In a 90-day study in rats using a functional-observational battery, dose levels of 64 and 200 mg hydroquinone/kg produced tremors, and 200 mg/kg produced depression of general activity. Neuropathological examinations were negative. Effects on humans. Cases of intoxication have been reported after oral ingestion of hydroquinone alone or of photographic developing agents containing hydroquinone. The major signs of poisoning included dark urine, vomiting, abdominal pain, tachycardia, tremors, convulsions and coma. Deaths have been reported after ingestion of photographic developing agents containing hydroquinone. In a controlled oral study on human volunteers, ingestion of 300-500 mg hydroquinone daily for 3-5 months did not produce any observable pathological changes in the blood and urine. Dermal applications of hydroquinone at concentration levels below 3% in different bases caused negligible effects in male volunteers from different human races. However, there are case reports suggesting that skin lightening creams containing 2% hydroquinone have produced leucoderma, as well as ochronosis. Hydroquinone (1% aqueous solution or 5% cream) has caused irritation (erythema or staining). Allergic contact dermatitis due to hydroquinone has been diagnosed. Combined exposure to hydroquinone and quinone airborne concentrations causes eye irritation, sensitivity to light, injury of the corneal epithelium, corneal ulcers and visual disturbances. There have been cases of appreciable loss of vision. Irritation has occurred at exposure levels of 2.25 mg/m3 or more. Long-term exposure causes staining of the conjunctiva and cornea and also opacity. Slowly developing inflammation and discoloration of the cornea and conjunctiva have resulted after daily hydroquinone exposure for at least two years of 0.05-14.4 mg/m3; serious cases have not occurred until after five or more years. One report described cases of corneal damage occurring several years after the exposure to hydroquinone had stopped. There are no adequate epidemiological data to assess the carcinogenicity of hydroquinone in humans. Effects on other organisms in the laboratory and field. The ecotoxicological behaviour of hydroquinone has to be related to its physicochemical properties, which induce sensitivity to light, pH and dissolved oxygen. Its ecotoxicity, which is generally high (e.g., 1 mg/litre for aquatic organisms), varies from species to species. The 72 h EC50 (growth) for the alga Selenastrum capricornutum was 0.335 mg/l. For Daphnia magna a 24 h EC50 of 0.09 mg/l and a 48 h EC50 of 0.29 mg/l was available. For Brachydanio rerio, Onchorhyncus mykiss and Pinephales promelas the lowest 96 ha LC50-values available were 0.17 mg/l; 0.097 mg/l and 0.044 mg/l, respectively. Algae, yeasts, fungi and plants are less sensitive to hydroquinone than the other organisms generally used for toxicity testing. However, within the same taxonomic group, the sensitivity of different species to hydroquinone may vary by a factor of 1000.