Energy-related pollutants in the environment: Use of short-term tests for mutagenicity in the isolation and identification of biohazards

Epler, J.L.; Larimer, Frank W.; Rao, T.K.; Nix, Carroll E.; Ho, Ti

doi:10.1289/ehp.782711

Cited by 35 publications

(4 citation statements)

References 34 publications

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“…In addition, hydroquinone also induced micronuclei in mice in vivo (92,98,202,203). As expected for a clastogen, hydroquinone was not mutagenic in Salmonella (38,202,204).…”

Section: Genetic Toxicologymentioning

confidence: 61%

Multiple-site carcinogenicity of benzene in Fischer 344 rats and B6C3F1 mice.

Huff

Haseman

DeMarini

et al. 1989

Environ Health Perspect

113

107

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Toxicology and carcinogenesis studies of benzene (CAS No. 71-43-2; greater than 99.7% pure) were conducted in groups of 60 F344/N rats and 60 B6C3FW mice of each sex for each of three exposure doses and vehicle controls. These composite studies on benzene were designed and conducted because of large production volume and widespread human exposure, because of the epidemiologic association with leukemia, and because previ. ous experiments were considered inadequate or inconclusive for determining carcinogenicity in laboratory animals. Using the results from 17-week studies, doses for the 2-year studies were selected based on clinical observations (tremors in higher dosed mice), on clinical pathologic findings (lymphoid depletion in rats and leukopenia in mice), and on body weight effects. Doses of 0, 50, 100, or 200 mg/kg body weight benzene in corn oil were administered by gavage to male rats, 5 days per week, for 103 weeks. Doses of 0, 25, 50, or 100 mg/kg benzene in corn oil were administered by gavage to female rats and to male and female mice for 103 weeks. Ten animals in each of the 16 groups were killed at 12 months, and necropsies were performed. Hematologic profiles were performed at 3-month intervals.For the 2-year studies, mean body weights of the top dose groups of male rats and of both sexes of mice were lower than those of the controls. Survivals of the top dose group of rats and mice of each sex were reduced; however, at week 92 for rats and week 91 for mice, survival was greater than 60% in all groups; most of the dosed animals that died before week 103 had neoplasia. Compound-related nonneoplastic or neoplastic effects on the hematopoietic system, Zymbal gland, forestomach, and adrenal gland were found both for rats and mice. Further, the oral cavity was affected in rats, and the lung, liver, Harderian gland, preputial gland, ovary, and mammary gland were affected in mice. Under the conditions of these 2-year gavage studies, there was clear evidence of carcinogenicity of benzene in male F344/N rats, female F344/N rats, male B6C3FW mice, and female B6C3FM mice. In male rats, benzene caused increased incidences of Zymbal gland carcinomas, squamous cell papillomas and squamous cell carcinomas of the oral cavity, and squamous cell papillomas and squamous cell carcinomas of the skin. In female rats, benzene caused increased incidences of Zymbal gland carcinomas and squamous cell papillomas and squamous cell carcinomas of the oral cavity. In male mice, benzene caused increased incidences of Zymbal gland squamous cell carcinomas, malignant lymphomas, alveolar/bronchiolar carcinomas and alveolar/bronchiolar adenomas or carcinomas (combined), Harderian gland adenomas, and squamous cell carcinomas of the preputial gland. In female mice, benzene caused increased incidences of malignant lymphomas, ovarian granulosa cell tumors, ovarian benign mixed tumors, carcinomas and careinosarcomas of the mammary gland, alveolar/bronchiolar adenomas, alveolar/bronchiolar carcinomas, and Zymbal gland squamous cell carcin...

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“…In addition, hydroquinone also induced micronuclei in mice in vivo (92,98,202,203). As expected for a clastogen, hydroquinone was not mutagenic in Salmonella (38,202,204).…”

Section: Genetic Toxicologymentioning

confidence: 61%

Multiple-site carcinogenicity of benzene in Fischer 344 rats and B6C3F1 mice.

Huff

Haseman

DeMarini

et al. 1989

Environ Health Perspect

113

107

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“…With few exceptions, HQ has been shown to be inactive as a direct mutagen in various shortterm assays. Negative results have been reported with various strains of S. typhimurium and E. coli, with or without metabolic activation, [117][118][119][120][121][122][123][124] in yeast (S. cerevisiae, strain D4), 117 and in Drosophila. 7,125,126 In addition, no evidence for mutagenicity was demonstrated in an in vivo mouse spot test 127 and in a dominant lethal assay in male rats following p.o.…”

Section: Genotoxicitymentioning

confidence: 99%

The Toxicology of Hydroquinone — Relevance to Occupational and Environmental Exposure

DeCaprio¹

1999

Critical Reviews in Toxicology

178

128

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Hydroquinone (HQ) is a high-volume commodity chemical used as a reducing agent, antioxidant, polymerization inhibitor, and chemical intermediate. It is also used in over-the-counter (OTC) drugs as an ingredient in skin lighteners and is a natural ingredient in many plant-derived products, including vegetables, fruits, grains, coffee, tea, beer, and wine. While there are few reports of adverse health effects associated with the production and use of HQ, a great deal of research has been conducted with HQ because it is a metabolite of benzene. Physicochemical differences between HQ and benzene play a significant role in altering the pharmacokinetics of directly administered when compared with benzene-derived HQ. 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. In cancer bioassays, HQ has reproducibly produced renal adenomas in male F344 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 F344 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. Epidemiological studies with HQ have demonstrated lower death rates and reduced cancer rates in production workers when compared with both general and employed referent populations. 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, 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. Myelotoxicity is also not associated with human exposure to HQ. These differences are likely due to significant route-dependent toxicokinetic factors. Fetotoxicity (growth retardation) accompanies repeated administration of HQ at maternally toxic dose levels in animal studies. HQ exposure has not been associated with other reproductive and developmental effects using current USEPA test guidelines. The skin pigment lightening properties of HQ appear to be due to inhibition of melanocyte tyrosinase. Adverse effects associated with OTC use of HQ in FDA-regulated products have been limited to a small number of cases of exogenous ochronosis, although higher incidences of this syndrome have been reported with inappropriate use of unregulated OTC products containing higher HQ concentrations. The most serious human health effect related to HQ is p...

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“…Bioassays 45 and immunological assays 46 are presently being evaluated for monitoring exposure to toxic materials. 47 ' 48 The evolution of the EPA priority pollutant list has been discussed. 49 A short review emphasizing the analysis of these compounds has been published.…”

Section: Compoundsmentioning

confidence: 99%