Chromosome aberrations and sister chromatid exchanges in chinese hamster ovary cells: Evaluations of 108 chemicals

Galloway, Sheila M.; Armstrong, Michael J.; Reuben, C.; Colman, Sue; Brown, B. M.; Cannon, Christopher P.; Bloom, Arthur D.; Nakamura, Frank T.; Ahmed, Maham; Duk, Soledad; Rimpo, J.; Margolin, Barry H.; Resnick, Michael A.; Anderson, Beth; Zeiger, Errol

doi:10.1002/em.2850100502

Cited by 587 publications

(244 citation statements)

References 64 publications

(10 reference statements)

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“…By gavage administration, 1,2-DCP induced hepatocellular adenomas in mice but not in rats 6) . In in vitro studies, 1,2-DCP exhibited weak mutagenicity at high concentrations in the Ames test 7−9) and induced sister chromatid exchange and chromosome aberration in CHO cells 10,11) . There is an unpublished report showing that the micronucleus in bone marrow cells was negative in mice administered 1,2-DCP by gavage 12) .…”

mentioning

confidence: 99%

Assessment of the Genotoxicity of 1,2‐Dichloropropane and Dichloromethane after Individual and Co‐exposure by Inhalation in Mice

Suzuki

Yanagiba

Suda

et al. 2014

Journal of Occupational Health

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205Tetsuya SUZUKI, et al.: Genotoxicity of 1,2-dichloropropane and Dichloromethane effects were greatly enhanced by simultaneous exposure to DCM. (J Occup Health 2014; 56: 205-214) Key words: 1,2-Dichloropropane, Co-exposure, Dichloromethane, Genotoxicity, InhalationRecently, the occurrence of cholangiocarcinoma cases was reported among the employees and former employees of an offset printing company in Osaka, Japan 1) . So far, 11 cancer patients have been diagnosed among 62 workers conducting offset color proof printing in this factory, and this surely shows an extremely high incidence rate of this kind of cancer compared with the national average during the same period. In addition, the ages of the workers at diagnosis were 25−45 years, and this is obviously much younger that in the general population. Later, more cases were found in factories, including other offset printing companies, in a national survey sponsored by the occupational health authorities 2) . The occurrence of cholangiocarcinoma in this industry is therefore suspected to be related to some factors in the workplaces.1,2-Dichloropropane (1,2-DCP) and dichloromethane (DCM) were the substances suspected of causing the cancer, since they were used as the ink cleaners in a large amounts and can easily evaporate into the air, meaning that the workers were therefore exposed to these chlorinated organic solvents at high concentrations. Our colleagues carried out an experiment to reproduce the working environment of the proof-printing room of this company in Osaka and concluded that the exposure concentrations might have been as high as several hundreds ppm for either 1,2-DCP or DCM under the conditions of ordinary work amount 3) , and the latter solvent showed 2-3 fold higher concentration than the former solvent because of the difference in evaporation rate. Other components in the cleaner included 1,1,1-trichloroethane, petroleum- Occurrence of cholangiocarcinoma was recently reported at a high incidence rate among the employees working for an offset printing company in Osaka, Japan. 1,2-Dichloropropane (1,2-DCP) and dichloromethane (DCM) are suspected to be the causes of the cancer, as they had been used as ink cleaners in large amounts. However, it is not clear whether these chlorinated organic solvents played a role in the occurrence of cholangiocarcinoma or why the incidence rate is so high among the workers in this industry. To provide possible evidence for this severe occupational problem, we investigated the genotoxic effects of 1,2-DCP and DCM. Methods: Male B6C3F1 and gpt Delta C57BL/6J mice were exposed by inhalation to the individual solvents or both solvents at multiple concentrations including the levels that were possibly present in the workplaces. The genotoxicity was analyzed by Pig-a gene mutation and micronuclei assays in peripheral blood and gpt mutation and comet assays in the livers of mice after repeated inhalation of 1,2-DCP or/and DCM. Results: The Pig-a mutant frequencies and micronuclei incidences were not significantl...

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confidence: 99%

Assessment of the Genotoxicity of 1,2‐Dichloropropane and Dichloromethane after Individual and Co‐exposure by Inhalation in Mice

Suzuki

Yanagiba

Suda

et al. 2014

Journal of Occupational Health

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“…Nur in menschlichen Hepatozyten fand sich bei hoher zytotoxischer BHT-Konzentration (11 mM) eine leicht erhöhte UDS-Rate (Chipman und Davies 1988), deren Relevanz aufgrund der starken Toxizität fraglich ist. Auch induziert BHT keine Schwesterchromatidaustausche (Abe und Sasaki 1977;Galloway et al 1987;Grillo und Dulout 1995Kawachi et al 1980;Shelby und Stasiewicz 1984;Williams et al 1984).…”

Section: Indikatortestsunclassified

“…Die an V79-Zellen (Ochi und Ohsawa 1985), CH-Don-Zellen (Abe und Sasaki 1977), CHL-Zellen (Ishidate 1983;Ishidate und Odashima 1977;Ishidate et al 1980Ishidate et al , 1984Kawachi et al 1980) und CHO-Zellen (Galloway et al 1987) durchgeführten Untersuchungen ließen keine Chromosomenaberrationen erkennen. Jedoch wurde in einer anderen Untersuchung an CHO-Zellen ein konzentrationsabhängiger Anstieg der Chromatidbrüche bis um das 150fache gegenüber der Kontrolle (ohne Vehikel) beobachtet (Grillo und Dulout 1995 20fache Erhöhung der Chromatidbrüche gegenüber der unbehandelten Kontrolle.…”

Section: Chromosomenaberrationstestsunclassified

Butylhydroxytoluol (BHT) [MAK Value Documentation in German language, 2004]

2012

The MAK‐Collection for Occupational Health and Safety

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Veröffentlicht in der Reihe Gesundheitsschädliche Arbeitsstoffe , 39. Lieferung, Ausgabe 2004 Der Artikel enthält folgende Kapitel: Allgemeiner Wirkungscharakter Wirkungsmechanismus Toxikokinetik und Metabolismus Aufnahme, Verteilung, Ausscheidung Metabolismus Erfahrungen beim Menschen Tierexperimentelle Befunde Akute Toxizität Subakute, subchronische und chronische Toxizität Wirkungen auf Haut und Schleimhäute Allergene Wirkung Reproduktionstoxizität Genotoxizität Kanzerogenität Bewertung

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“…Without S9, the response in this test was equivocal, with a significant increase in chromosomal aberrations observed only at 1000 µg/mL (Galloway, 1985(Galloway, , 1987NTP, 1992).…”

Section: In Vitro Testingmentioning

confidence: 99%

Scientific Opinion on the use of Resorcinol as a food additive

2010

EFSA Journal

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Following a request from the European Commission (EC), the Panel on Food Additives and Nutrient Sources added to Food (ANS) was asked to deliver a scientific opinion on the safety of resorcinol when used as an antioxidant in crustaceans. Resorcinol is a specific inhibitor of polyphenol oxidase and therefore it can act as an anti-browning agent in fresh, frozen and deep-frozen crustaceans. Resorcinol is rapidly absorbed from the gastrointestinal tract, metabolised extensively to sulphate and/or glucuronic acid conjugates and excreted primarily in the urine. Resorcinol causes moderate acute toxicity in rats. Subchronic toxicity studies in rats and mice indicate a steep dose-response curve for lethality. Carcinogenicity studies in rats and mice demonstrated the lack of carcinogenic activity of resorcinol. However, clinical signs of toxicity were seen at approximately 100 mg resorcinol/kg bw/day (5 days per week) and above. Based on the available data from in vitro and in vivo genotoxicity tests the Panel concluded that there is no concern with respect to genotoxicity. Resorcinol has no adverse effects on the developing fetus nor does it cause maternal toxicity in rats and rabbits. The Panel considers the acute neurological signs of toxicity to be the pivotal adverse effect of resorcinol and based on the NOAEL of 36 mg resorcinol/kg bw/day in the carcinogenicity study in rats and using an uncertainty factor of 300 the Panel established an ADI of 0.12 mg/kg bw/day for resorcinol. The conservative estimates of acute consumption of shrimps (the only category for which experimental data were reported) indicate that dietary exposure to resorcinol for adults and for children would exceed the ADI when the residual concentration of resorcinol in whole raw shrimps is above 35 mg/kg. The Panel notes that this value is only applicable if other uses of resorcinol are excluded. KEY WORDS Resorcinol, CAS SUMMARYFollowing a request from the European Commission to the European Food Safety Authority (EFSA), the Scientific Panel on Food Additives and Nutrient Sources added to Food (ANS) was asked to provide a scientific opinion on the safety of resorcinol when used as an antioxidant in crustaceans.Resorcinol is a specific inhibitor of polyphenol oxidase and therefore it can act as an anti-browning agent in fresh, frozen and deep-frozen crustaceans. Specifications for resorcinol indicated by the petitioner are: the minimum purity of resorcinol is 99 % (stated range of 99.0-100.5 % by iodometry assay), insoluble matter is set at 0.005 % and the residue after ignition 0.01 % maximum. The antibrowning agent intended to be authorised contains resorcinol as a main ingredient (more than 99.5 %) and citric or ascorbic acid at less than 0.3 %.The petitioner proposes to use resorcinol at a concentration of 5 to 7 g/L in the dipping solution for a dipping time of 4-5 minutes. Under these treatment conditions, the residual resorcinol measured in raw shrimps (whole product) was 120 mg/kg, in edible parts of raw shrimps was 30 mg/kg, and ...

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Chromosome aberrations and sister chromatid exchanges in chinese hamster ovary cells: Evaluations of 108 chemicals

Cited by 587 publications

References 64 publications

Assessment of the Genotoxicity of 1,2‐Dichloropropane and Dichloromethane after Individual and Co‐exposure by Inhalation in Mice

Assessment of the Genotoxicity of 1,2‐Dichloropropane and Dichloromethane after Individual and Co‐exposure by Inhalation in Mice

Butylhydroxytoluol (BHT) [MAK Value Documentation in German language, 2004]

Scientific Opinion on the use of Resorcinol as a food additive

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