Mutagenic activity of chemicals identified in drinking water

Simmon, Vincent F.; Kauhanen, K.; Mortelmans, Kristien; Tardiff, Robert G.

doi:10.1016/0165-1161(78)90337-0

Cited by 124 publications

(100 citation statements)

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“…The results have been generally negative. For instance, two groups reported that chloroform failed to induce mutations in Salmonella typhimurium (21,22), and chloroform was also negative in a sex-linked recessive lethal test conducted in Drosophila melanogaster (23). Most recently, chloroform was selected as one of several prototype chemicals to be evaluated in a comprehensive battery of short term tests for carcinogenicity.…”

Section: Discussionmentioning

confidence: 99%

Mechanistic Considerations for Carcinogenic Risk Estimation: Chloroform

Reitz¹,

Fox²,

Quast³

1982

Environmental Health Perspectives

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Chloroform has been reported to induce cancer in rodents after chronic administration of high doses by gavage. However, the interpretation of these findings is hampered by a lack of knowledge concerning the relative roles of genetic and nongenetic mechanisms in these bioassays. The present studies were carried out in male B6C3F1 mice in order to investigate the potential of chloroform to induce genetic damage and/or organ toxicity at the sites where tumors have been observed in the various bioassays. These studies revealed that carcinogenic doses of chloroform produced severe necrosis at the sites where tumors later developed. This was demonstrated by light microscopy as well as by determination of the cellular regeneration index following administration of 3H-thymidine. Noncarcinogenic doses of chloroform failed to induce these responses. In contrast, studies of DNA alkylation and DNA repair in vivo failed to give any indication that chloroform had produced the type of genetic alterations associated with known genotoxic chemicals. These data suggest that the-primary mechanism of chloroform-induced carcinogenesis is nongenetic in nature. If the same mechanism predominates in man, there should be little to no carcinogenic risk associated with exposure to noncytotoxic levels of chloroform.

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Section: Discussionmentioning

confidence: 99%

Mechanistic Considerations for Carcinogenic Risk Estimation: Chloroform

Reitz¹,

Fox²,

Quast³

1982

Environmental Health Perspectives

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“…Two members of this group (borneol,.016] and isobornyl propionate, .131]) consistently gave negative results in the Ames assay when incubated at a concentration of up to 5000 µg/plate with a variety of Salmonella typhimurium strains including TA97, TA98, TA100, TA1535, TA1537 and TA1538 with or without metabolic activation (Simmon et al, 1977;Wild et al, 1983;Azizan and Blevins, 1995).…”

Section: In Vitromentioning

confidence: 99%

Scientific Opinion on Flavouring Group Evaluation 87 Revision 1 (FGE.87Rev1): Consideration of bicyclic secondary alcohols, ketones and related esters evaluated by JECFA (63rd meeting) structurally related to bicyclic secondary alcohols, ketones and relat

Flavourings¹

2012

EFSA Journal

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Flavouring Group Evaluation 87, Revision 1 EFSA Journal 2012;10(2):2564 2 through a stepwise approach that integrates information on structure-activity relationships, intake from current uses, toxicological threshold of concern, and available data on metabolism and toxicity. The Panel agrees with the application of the Procedure as performed by the JECFA for all 17 substances considered in this FGE and agrees with the JECFA conclusion, "No safety concern at estimated levels of intake as flavouring substances" based on the MSDI approach. Besides the safety assessment of these flavouring substances, the specifications for the materials of commerce have also been considered for the substances evaluated through the Procedure and for two substances, [FL-no: This consideration deals with 17 bicyclic secondary alcohols, ketones and related esters, which are in the Register and which were evaluated by the JECFA at its 63 rd meeting.The revision is made due to consideration of two additional substances [FL-no: 02.100 and 02.101] compared to the previous version. These two substances are alpha,beta-unsaturated substances which have been considered with respect to genotoxicity in FGE.211 and FGE.212Rev1, and the Panel concluded that the data available ruled out the concern for genotoxicity and thus concluded that the two substances can be evaluated through the Procedure in this FGE.87Rev1. EU production volume on two substances [FL-no: 09.153 and 09.319] and new information on stereoisomerism for 13 substances 02.038, 02.059, 07.159, 09.017, 09.082, 09.131, 09.153, 09.176, 09.218, 09.319, 09.456 and 09.457] are also included.The Panel concluded that all 17 substances are structurally related to the group of four bicyclic secondary alcohols, ketones and related evaluated by EFSA in the Flavouring Group Evaluation 47 (FGE.47).The Panel agrees with the application of the Procedure as performed by the JECFA for the 17 bicyclic secondary alcohols, ketones and related esters. It was concluded at step A3 of the Procedure that the 17 substances do not pose a safety concern when used as flavouring substances at estimated levels of intake, based on the MSDI approach.For all 17 substances evaluated through the Procedure use levels are needed to calculate the mTAMDIs in order to identify those flavouring substances that need more refined exposure assessments and to finalise the evaluation.In order to determine whether the conclusion for the JECFA-evaluated substances can be applied to the materials of commerce, it is necessary to consider the available specifications. Specifications are available for all the materials of commerce. For two of the candidate substances [FL-no: 02.100 and 02.101] the stereoisomeric composition has not been specified. Thus, for these two JECFA-evaluated substances [FL-no: 02.100 and 02.101] the Panel has reservations (information on the stereoisomeric composition is lacking).For the remaining 15 JECFA-evaluated substances

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“…For all substances, use levels are needed to calculate the mTAMDIs. consistently gave negative results in the Ames assay when incubated at a concentration of up to 5000 µg/plate with a variety of Salmonella typhimurium strains including TA97, TA98, TA100, TA1535, TA1537 and TA1538 with or without metabolic activation (Simmon et al, 1977;Wild et al, 1983;Azizan and Blevins, 1995).…”

Section: Efsa Considerationsmentioning

confidence: 99%

Scientific Opinion on Flavouring Group Evaluation 87, Revision 2 (FGE.87Rev2): Consideration of bicyclic secondary alcohols, ketones and related esters evaluated by JECFA (63rd meeting) structurally related to bicyclic secondary alcohols, ketones and rela

Flavourings¹

2014

EFSA Journal

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The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to consider evaluations of flavouring substances assessed since 2000 by the Joint FAO/WHO Expert Committee on Food Additives (the JECFA), and to decide whether further evaluation is necessary, as laid down in Commission Regulation (EC) No 1565/2000. The present consideration concerns a group of 19 bicyclic secondary alcohols, ketones and related esters evaluated by the JECFA at the 63 rd meeting in 2004. This revision of FGE.87 is made due to inclusion of two additional substances Nookatone .089] and 4,4a,5,6-tetrahydro-7-methylnapthalen-2(3H)-one ] cleared for genotoxicity concern in FGE.213 Rev1. The substances were evaluated through a stepwise approach that integrates information on structure-activity relationships, intake from current uses, toxicological threshold of concern, and available data on metabolism and toxicity. The Panel agrees with the application of the Procedure as performed by the JECFA for all substances considered in this FGE and for 18 substances the Panel agrees with the JECFA conclusion, "No safety concern at estimated levels of intake as flavouring substances" based on the MSDI approach. For one substance .136], a production volume for Europe is not available, which precludes the finalisation of the evaluation by EFSA of this substance. Besides the safety assessment of these flavouring substances, the specifications for the materials of commerce have also been considered for the substances evaluated through the Procedure and for all 19 substances, the information is adequate. This consideration deals with 19 bicyclic secondary alcohols, ketones and related esters, which are in the Register and which were evaluated by the JECFA at its 63 rd meeting.The revision is made due to consideration of two additional substances nootkatone and 4,4a,5,6-tetrahydro-7-methylnapthalen-2(3H)-one [FL-no: 07.089 and 07.136] compared to the previous version. These two substances are α,β-unsaturated alicyclic ketones which have been considered with respect to genotoxicity in FGE.213Rev1, and the Panel concluded that the data available ruled out the concern for genotoxicity and thus concluded that the two substances can be evaluated through the Procedure in this FGE.87Rev2.The Panel concluded that all 19 substances are structurally related to the group of bicyclic secondary alcohols, ketones and related evaluated by EFSA in the Flavouring Group Evaluation 47 (FGE.47Rev1).The Panel agrees with the application of the Procedure as performed by the JECFA for the 19 bicyclic secondary alcohols, ketones and related esters. It was concluded at step A3 of the Procedure that 18 substances do not pose a safety concern when used as flavouring substances at estimated levels of intake, based on the MSDI approach. For one substance ], the evaluation through the Procedure could not be finalised because of absence of an EU production volume.For all 19 substances evaluated through the Proce...

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Mutagenic activity of chemicals identified in drinking water

Cited by 124 publications

References 0 publications

Mechanistic Considerations for Carcinogenic Risk Estimation: Chloroform

Mechanistic Considerations for Carcinogenic Risk Estimation: Chloroform

Scientific Opinion on Flavouring Group Evaluation 87 Revision 1 (FGE.87Rev1): Consideration of bicyclic secondary alcohols, ketones and related esters evaluated by JECFA (63rd meeting) structurally related to bicyclic secondary alcohols, ketones and relat

Scientific Opinion on Flavouring Group Evaluation 87, Revision 2 (FGE.87Rev2): Consideration of bicyclic secondary alcohols, ketones and related esters evaluated by JECFA (63rd meeting) structurally related to bicyclic secondary alcohols, ketones and rela

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