Screening of safrole, eugenol, their ninhydrin positive metabolites and selected secondary amines for potential mutagenicity

Green, Nancy R.; Savage, Jane R.

doi:10.1016/0027-5107(78)90257-9

Cited by 62 publications

(29 citation statements)

References 7 publications

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“…EUG was not mutagenic to Salmonella typhimuri- um TA1964, TA1535, TA1532, TA1531, TA1530, TA100 and TA98 with or without metabolic activation Dorange et al, 1977;Green and Savage, 1978;Swanson et al, 1979;Eder et al, 1980), and not mutagenic to Escherichia coli WP2 uvrA with or without metabolic activation (Sekizawa and Shibamoto, 1982). However, EUG induced chromosomal aberrations in Chinese hamster ovary cells with or without metabolic activation (Stich et al, 1981;NTP, 1983).…”

Section: Discussionmentioning

confidence: 99%

Lack of modifying effects of eugenol on development of lung proliferative lesions induced by urethane in transgenic mice carrying the human prototype c-Ha-ras gene.

et al. 2001

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To investigate the modifying effects of eugenol (EUG), a component of cigarette smoke, on lung carcinogenesis, male and female transgenic mice carrying the human prototype c-Ha-ras gene (rasH2 mice) were given a single intraperitoneal injection of 250 mg/kg urethane (UR) or saline, followed by a diet containing 6,000 ppm EUG or basal diet for 26 weeks. Their non-transgenic CB6F1 littermates (non-Tg mice) were also treated in the same manner. In both male and female rasH2 mice, alveolar/bronchiolar hyperplasias, adenomas and carcinomas were observed in all UR-treated groups. However, there were no significant intergroup differences in the incidences and multiplicities of these lesions between the UR alone and UR EUG groups. In non-Tg mice, alveolar/bronchiolar hyperplasias, adenomas or carcinomas were sporadically observed in UR-treated groups of both sexes, with no significant differences in the incidences and multiplicities between the UR alone and UR EUG groups. There were no intergroup differences between them in the PCNA-positive ratios of adenomas or carcinomas and the areas of adenomas or carcinomas to the whole lung area examined. The present results suggest that the EUG treatment does not exert modifying effects on lung carcinogenesis induced by UR in both male and female rasH2 mice and non-Tg mice.

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Section: Discussionmentioning

confidence: 99%

Lack of modifying effects of eugenol on development of lung proliferative lesions induced by urethane in transgenic mice carrying the human prototype c-Ha-ras gene.

et al. 2001

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“…No mutagenicity was found in the standard Ames assay when various strains of Salmonella typhimurium (TA97a, TA98, TA100, TA102, TA1535, TA1537, TA1538, TA1530, TA1531, TA1532 and TA1964) (Green and Savage, 1978;Haworth et al, 1978;Andrews et al, 1980;Florin et al, 1980;Haworth et al, 1983;Mortelmans et al, 1986;Zeiger et al, 1987;Karekar et al, 1996;King, 2003).…”

Section: In Vitromentioning

confidence: 99%

“…In a host-mediated assay in which S. typhimurium strain TA1950, TA1951, TA1952 or TA1964 was injected intraperitoneally into mice followed by an intramuscular injection of 800 mg/kg bw of piperidine or pyrrolidine, no mutagenicity was observed (Green and Savage, 1978).…”

Section: In Vitromentioning

confidence: 99%

Scientific Opinion on Flavouring Group Evaluation 86, Revision 2 (FGE.86Rev2): Consideration of aliphatic and arylalkyl amines and amides evaluated by JECFA (65th meeting)

Publication¹

2015

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 (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 30 aliphatic and arylalkyl amines and amides evaluated by JECFA at the 65 th meeting in 2005. This revision is required owing to additional available toxicity data on piperine .003] and deca-(2E,4E)-dienoic acid isobutyl-amide .091]. The substances were evaluated through a stepwise approach that integrates information on structure-activity relationships, intake from current uses, toxicological thresholds of concern and available data on metabolism and toxicity. The Panel agrees with JECFA's conclusion "No safety concern at estimated levels of intake as flavouring substances" based on the Maximised Survey-derived Daily Intake (MSDI) approach for all substances considered in this FGE. Besides the safety assessment of these flavouring substances, the specifications for the materials of commerce have also been considered and for all 30 substances, the information is adequate. The previous version of this consideration, FGE.86Rev1, dealt with 34 aliphatic and arylalkyl amines and amides which are in the Register and which were evaluated by JECFA at its 65 th meeting. The Panel concluded that no structurally related substances to support the evaluation in a corresponding Flavouring Group Evaluation (FGE) was available. © European FoodSince the publication of FGE.86Rev1, the Industry has informed that four of the substances, 16.049, 16.093 and 16.094], are no longer used as flavouring substances in Europe and will therefore not be further considered in this FGE. The present consideration therefore only deals with 30 flavouring substances.In FGE.86Rev1, the Panel agreed with the application of the Procedure as performed by JECFA for 27 of the 30 substances. For two substances, piperine .003] and deca-(2E,4E)-dienoic acid isobutyl-amide .091], the Panel did not agree with JECFA that appropriate studies are available for deriving NOAELs and concluded that additional toxicity data are required for these two substances.The present revision of FGE.86Rev1 is due to the submission of the requested toxicity data for [FLno: 14.003 and 16.091]. Based on the results of two 90-day oral toxicity studies received by EFSA the Panel now concludes that these two substances are not of safety concern when used as flavouring substances at the estimated levels of exposure based on the MSDI approach.For N-isopentylidene isopentylamine .017] the Panel concluded that this substance can be metabolised to innocuous products and accordingly evaluated along the A-side of the Procedure (while JECFA evaluated .017] along the B-side). Like JECFA the Panel concluded that ] is of no safety concern at estimated level of intake, ba...

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“…Based on these normal use levels mTAMDI figures (see Table 2.2.2) can be calculated (EFSA, 2004d (Green & Savage, 1978;Haworth et al, 1978;Andrews et al, 1980;Florin et al, 1980;Haworth et al, 1983;Mortelmans et al, 1986;Zeiger et al, 1987;Karekar et al, 1996;King, 2003).…”

Section: Efsa Considerationsmentioning

confidence: 99%

Flavouring Group Evaluation 86, (FGE.86) - Consideration of aliphatic and aromatic amines and amides evaluated by JECFA (65th meeting) - Scientific Opinion of the Panel on Food Additives - Flavourings, Processing Aids and Materials in Contact with Food

2008

EFSA Journal

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The present consideration concerns 35 aliphatic and aromatic amines and amides evaluated by the JECFA (65 th meeting). The Panel concluded that no corresponding FGE is available.Further two substances were evaluated by the JECFA in this group, but these are not in the Register (1-amino-2-propanol and acetamide; JECFA-no: 1591 and 1592, respectively).The Panel agreed with the application of the Procedure as performed by the JECFA for 28 of the 35 substances. The JECFA concluded the five substances 14.003, 16 11.004, 11.005, 11.007, 11.014, 11.015, 11.016, 11.017, 11.018, 11.020, 11.021, 11.023, 11.025, 11.026, 14.080, 14.133, 14.141, 14.168, 16.049, 16.052, 16.091 and 16.092] the EU production figures are anticipated.For 22 substances evaluated by the JECFA through the Procedure use levels have been provided by the Industry 11.004, 11.005, 11.007, 11.014, 11.015, 11.016, 11.018, 11.020, 11.021, 11.023, 11.025, 11.026, 14.080, 14.133, 14.141, 16.049, 16. 14.141, 16.052, 16.091, 16.092, 16.093 and 16.094] the intakes, estimated on the basis of the mTAMDI approach, exceed the threshold for their structural classes. Therefore more reliable exposure data are required. On the basis of such additional data, these flavouring substances should be considered using the Procedure. Subsequently, additional data might become necessary.For the remaining 13 substances 11.003, 11.006, 11.009, 11.017, 14.003, 14.010, 14.064, 14.167, 14,168, 16.006, 16.013 and 16.053] use levels are needed to calculate the mTAMDIs in order to identify those flavouring substances that need more refined exposure assessment and to finalise the evaluation.In order to determine whether the conclusion for the 35 JECFA evaluated substances can be applied to the materials of commerce, it is necessary to consider the available specifications:Specifications including complete purity criteria and identity tests are available for 30 of the 35 JECFA evaluated substances. For one substance .013] information on the stereoisomeric composition is lacking and for one substance .017] composition of mixture has to be specified. For two substances ] data on solubility are needed, and for three substance 14.168 and 16.094] identity tests are missing.Thus, for seven substances 11.017, 14.064, 14.168, 16.013, 16.053 and 16.094] the Panel has reservations (no European production volumes available, preventing them from being evaluated using the Procedure, and/or missing data on specifications and/or information on stereoisomerism /composition).For seven of the 35 evaluated substances the Panel did not agree with the JECFA application of the Procedure and additional toxicity data are required for five of the seven substances [FLno: 11.014, 14.003, 16.091, 16.093 and 16.094]. One substance cannot be evaluated through the Procedure due to concern with respect to genotoxicity/carcinogenicity .049] and one substance ] is evaluated along the A-side, while the JECFA evaluated it along the B-side.Overall, for the remaining 23 of the 35 JECFA evaluated aliphatic and ar...

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Screening of safrole, eugenol, their ninhydrin positive metabolites and selected secondary amines for potential mutagenicity

Cited by 62 publications

References 7 publications

Lack of modifying effects of eugenol on development of lung proliferative lesions induced by urethane in transgenic mice carrying the human prototype c-Ha-ras gene.

Lack of modifying effects of eugenol on development of lung proliferative lesions induced by urethane in transgenic mice carrying the human prototype c-Ha-ras gene.

Scientific Opinion on Flavouring Group Evaluation 86, Revision 2 (FGE.86Rev2): Consideration of aliphatic and arylalkyl amines and amides evaluated by JECFA (65th meeting)

Flavouring Group Evaluation 86, (FGE.86) - Consideration of aliphatic and aromatic amines and amides evaluated by JECFA (65th meeting) - Scientific Opinion of the Panel on Food Additives - Flavourings, Processing Aids and Materials in Contact with Food

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