NIOSH REL: 15-min ceiling 2, IDLH 50; OSHA PEL: TWA 2;
ACGIH TLV: TWA 2 (adopted).
LogP：
0.59 at 20℃
物理描述：
Hydroquinone appears as light colored crystals or solutions. May irritate the skin, eyes and mucous membranes. Mildly toxic by ingestion or skin absorption.
Hydroquinone is absorbed through the skin and metabolized primarily to sulfate and glucuronide conjugates, which are excreted in the urine.[DHHS/NTP: Nomination Profile Hydroquinone
/This study/ investigated the metabolism of hydroquinone in naive and hydroquinone pretreated male Sprague-Dawley rats. (14)C hydroquinone was administered by gavage in single doses of 5, 30, or 200 mg/kg to naive rats. Hydroquinone was given repeatedly by gavage to male rats at 200 mg/kg for 4 consecutive days followed by a single dose with 200 mg/kg of (14)C hydroquinone. In separate studies rats were fed 5.6% unlabeled hydroquinone in the diet for 2 days or were dosed by gavage with 311 mg/kg (14)C hydroquinone. The excretion patterns of (14)C hydroquinone and its metabolites were similar for rats dosed singly or repeatedly. Rats given a single dose of 200 mg/kg of (14)C hydroquinone excreted 91.9% of the dose in the urine within 2-4 days; 3.8% was excreted in the feces, about 0.4% was excreted in expired air, and 1.2% remained in the carcass. Radioactivity was widely distributed throughout the tissues with higher concentrations in the liver and kidneys. A decrease in (14)C tissue concentrations occurred from 48 to 96 hr. The only radiolabeled compounds in the urine were hydroquinone (1.1-8.6% of the dose), hydroquinone monosulfate (25-42%), and hydroquinone monoglucuronide (56-66%). Similar findings were observed for rats given hydroquinone in the feed. There were no significant increases from controls for absolute or relative liver weights, liver microsomal protein concentrations, cytochrome b-5, cytochrome P450 or cytochrome c reductase activity in rats dosed repeatedly with 200 mg/kg hydroquinone. Cytochrome P450 values were slightly but significantly decreased in rats dosed repeatedly with hydroquinone compared with controls.
The metabolite 2-(S-glutathionyl)hydroquinone is formed when a microsomal incubation mixture containing either benzene or phenol is supplemented with glutathione. This metabolite is derived from the conjugation of benzoquinone, an oxidation product of hydroquinone. However, neither the glutathione conjugate or its mercapturate, N-acetyl-S-(2,5-dihydroxyphenyl)-L-cysteine, have been identified as metabolites resulting from in vivo metabolism of benzene, phenol, or hydroquinone. To determine if a hydroxylated mercapturate is produced in vivo, we treated male Sprague-Dawley rats with either benzene (600 mg/kg), phenol (75 mg/kg), or hydroquinone (75 mg/kg) and collected the urine for 24 hr. HPLC coupled with electrochemical detection confirmed the presence of a metabolite that was chromatographically and electrochemically identical to N-acetyl-S-(2,5-dihydroxyphenyl)-L-cysteine. The metabolite was isolated from the urine samples and treated with diazomethane to form the N-acetyl-S-(2,5-dimethoxyphenyl)-L-cysteine methyl ester derivative. The mass spectra obtained from these samples were identical to that of an authentic sample of the derivative. The results of these experiments indicate that benzene, phenol, and hydroquinone are metabolized in vivo to benzoquinone and excreted as the mercapturate, N-acetyl-S-(2,5-dihydroxyphenyl)-L- cysteine.
IDENTIFICATION AND USE: Hydroquinone (HQ) is an aromatic compound in the form of light tan to gray crystals. It is a high-volume commodity chemical used as a reducing agent, antioxidant, polymerization inhibitor, chemical stabilizer, chemical intermediate, and photographic reducer and developer. It is also used in skin lighteners, in cosmetics, hair dye, glue, and a medication to treat dyschromias. HUMAN EXPOSURE: A great deal of research has been conducted with HQ because it is a metabolite of benzene. In workers engaged in the manufacture, HQ dust oxidizes to brown benzoquinone. This material causes pigmentation of the eye and, in some cases, permanent corneal damage. There are reported cases of keratitis and discoloration of the conjunctiva among men exposed to concentrations ranging from 10 to 30 mg of vapor or dust of HQ per cubic meter of air. Ingestion of 1 g by an adult has caused dizziness, sense of suffocation, increased rate of respiration, vomiting, pallor, muscular twitching, headache, dyspnea, cyanosis and collapse and eventually death due to respiratory failure. Upon ingestion urine is green or brownish-green in color and continues to darken on standing. Five hundred forty-four (544) crewmen aboard a large USA Navy vessel developed GI disease characterized by acute onset of nausea, vomiting, abdominal cramps, and diarrhea which was found to be due to hydroquinone contamination of the chilled water system by automatic photo developing machines on the ship. HQ is only weakly positive in in vivo chromosomal assays when expected human exposure routes are used. Chromosomal effects are increased significantly when parenteral or in vitro assays are used. Hydroquinone impairs several leukocyte cell functions, which alter the immune response. It evokes pro-inflammatory properties in endothelial cells that are triggered by the enhancement of NF-kappaB nuclear translocation-dependent gene transcription. Parenteral administration of HQ is associated with changes in several hematopoietic and immunologic endpoints. This toxicity is more severe when combined with parenteral administration of phenol. It is likely that oxidation of HQ within the bone marrow compartment to the semiquinone or p-benzoquinone (BQ), followed by covalent macromolecular binding, and is critical to these effects. Bone marrow and hematologic effects are generally not characteristic of HQ exposures in animal studies employing routes of exposure other than parenteral. Enhanced Ras signaling increases both hydroquinone-mediated growth inhibition in yeast and genotoxicity in mammalian hematopoietic suggesting that HQ toxicity is modulated by Ras signaling and individuals with abnormal Ras signaling could be more vulnerable to developing myeloid diseases after exposure. Hydroquinone also increases proliferation of CFU-GM progenitor cells in mice with Nf1 null bone marrow relative to WT, the same cell type associated with benzene-associated leukemia. It is confirmed animal carcinogen with unknown relevance to humans. ANIMAL STUDIES: In cancer bioassays, HQ has reproducibly produced renal adenomas in male rats. The mechanism of tumorigenesis is unclear but probably involves a species-, strain-, and sex-specific interaction between renal tubule toxicity and an interaction with the chronic progressive nephropathy that is characteristic of aged male rats. Mouse liver tumors (adenomas) and mononuclear cell leukemia (female rat) have also been reported following HQ exposure, but their significance is uncertain. Various tumor initiation/promotion assays with HQ have shown generally negative results. In two-year studies in rats of each sex given hydroquinone in deionized water by gavage, nearly all male rats and most female rats in all vehicle control and dosed groups had nephropathy. The severity of this disease was judged to be greater in high dose male rats. The data on the effect of HQ on development are conflicting, with several studies reporting minimal to no treatment -related effects on duration of gestation, mean litter size, fetal viability, or lactation index in rats fed diets containing HQ. However, one study reports that female rats fed 0.5 g of hydroquinone in their diet during pregnancy had higher rates of fetal resorption than controls (100% versus 41% of the dams), and a greater number of the total implantations were resorbed (27% versus 11%). HQ was not mutagenic in Salmonella typhimurium strains TA98, TA100, TA1535, or TA1537 with or without exogenous metabolic activation. It induced trifluorothymidine resistance in mouse L5178Y/TK lymphoma cells in the presence or absence of metabolic activation, and induced sister chromatid exchanges in Chinese hamster ovary cells both with or without exogenous metabolic activation and caused chromosomal aberrations in the presence of activation. HQ also induced aneuploidy in yeast by delaying the cell cycle at the G2/M transition.
Evaluation: There is inadequate evidence in humans for the carcinogenicity of hydroquinone. There is limited evidence in experimental animals for the carcinogenicity of hydroquinone. Overall evaluation: Hydroquinone is not classifiable as to its carcinogenicity to humans (Group 3).
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
A3；已确认对动物有致癌性，但对人类的相关性未知。
A3; Confirmed animal carcinogen with unknown relevance to humans.
A toxicology review of hydroquinone noted several reports indicating relatively rapid absorption of hydroquinone via the oral route, including a study involving rats that ingested 3% hydroquinone in developer solution. In addition, in CD and F344 rats dosed with 350 mg/kg, >90% absorption was measured in blood levels, with peak levels observed within 1 hr.[DHHS/NTP: Nomination Profile Hydroquinone
Following intravenous (iv) administration of radiolabeled hydroquinone, radioactivity (either hydroquinone or a metabolite) was detected within 2 hr in bone marrow and thymus of rats given 1.2-12 mg/kg. Radioactivity was also detected in the liver and bone marrow of these rats up to 24 hr. Whether given in single or repeated oral doses, radioactivity was found in various rat tissues, with the highest concentrations in the liver and kidneys. Following i.v. administration of radiolabeled hydroquinone in dogs, radioactivity was found in the skin, liver, and intestine. When mice were administered 75 mg/kg radiolabeled hydroquinone by intraperitoneal (ip) injection, radioactivity was detected covalently bound to proteins in the liver, kidneys, blood, and bone marrow, with 10-fold higher specific activity in the liver than in the bone marrow...[DHHS/NTP: Nomination Profile Hydroquinone
When 2% [(14)C]-hydroquinone was administered to human forearms (n = 4 males) in an unspecified cream, hydroquinone moved rapidly and continuously into the stratum corneum and radiolabel was detected in plasma samples within 0.5 hr. Over an 8 hr plasma sampling period, hydroquinone levels peaked at 4 hr (0.04 equivalents/ mL). Following application of the 2% cream on the foreheads of 6 male volunteers for 24 hr, the recovery of hydroquinone in urine was 45.3% (SD = 11.2%).[DHHS/NTP: Nomination Profile Hydroquinone
Human absorption of hydroquinone upon topical application is less efficient than with oral administration. When absorption was measured as elimination 10 of hydroquinone via urine following application (2.0% in alcohol) to the foreheads of human volunteers (6 males per preparation) for 24 hr, the average percutaneous absorption reported was 57% (SD = 11%) with peak elimination within 12 hr and complete elimination by 5 days. The addition of a sunscreen (3.0% Escalol 507) significantly decreased the absorption (26%, SD = 14%), and the addition of a penetration enhancer (0.5% Azone) did not significantly increase absorption in the presence or absence of the sunscreen (35%, SD = 17% and 66%, SD = 13%, respectively).[DHHS/NTP: Nomination Profile Hydroquinone
