The Metabolism of Thiophen in the Rabbit and the Rat

Bray, H. G.; Carpanini, F.M.B.; Waters, Brian

doi:10.3109/00498257109044387

Cited by 37 publications

(37 citation statements)

References 38 publications

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“…comprising not more than about 1 % of the dose) excreted in the urine (Hickman et al, 1992), contrary to the results of Bray et al (Bray et al, 1971). It is noted that 2-thienyl mercapturic acid was also identified as a less important metabolite by Bray et al (1971) and that the two studies differ in route of administration. The oral route of administration (Bray et al, 1971) results in higher metabolic conversion as compared to the intraperitoneal one (Hickman et al, 1992).…”

Section: ])contrasting

confidence: 55%

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Scientific Opinion on Flavouring Group Evaluation 21, Revision 3 (FGE.21Rev3): Thiazoles, thiophenes, thiazoline and thienyl derivatives from chemical groups 29 and 30

Flavourings¹

2012

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 evaluate 59 flavouring substances in the Flavouring Group Evaluation 21, including an additional three substances in this Revision 3, using the Procedure in Commission Regulation (EC) No 1565/2000. Since the publication of the last revision of this FGE, the EFSA has been requested to evaluate three additional substances 15.079 and 15.135], which have been included in the present revision of FGE.21. Seven of the substances 15.086, 15.090, 15.099, 15.114, 15.119 and 15.133] were considered to have genotoxic potential. The remaining 52 substances were evaluated through a stepwise approach (the Procedure) that integrates information on structure-activity relationships, intake from current uses, toxicological threshold of concern, and available data on metabolism and toxicity. The Panel concluded that 26 substances [FLno: 15.038, 15.039, 15.044, 15.050, 15.051, 15.052, 15.058, 15.061, 15.062, 15.063, 15.067, 15.068, 15.069, 15.071, 15.078, 15.080, 15.082, 15.084, 15.085, 15.087, 15.089, 15.098, 15.108, 15.115, 15.116 and 15.118] do not give rise to safety concerns at their levels of dietary intake, estimated on the basis of the MSDI approach. For the remaining 26 candidate substances 15.040, 15.042, 15.043, 15.045, 15.054, 15.055, 15.057, 15.064, 15.070, 15.072, 15.074, 15.076, 15.077, 15.079, 15.088, 15.091, 15.092, 15.093, 15.094, 15.096, 15.097, 15.106, 15.107, 15.129 and 15.135] evaluated through the Procedure, no appropriate NOAEL was available and additional data are required. Besides the safety assessment of these flavouring substances, the specifications for the In the present FGE.21Rev3, the 59 flavouring substances include five-and six-membered sulphurcontaining aromatic and non-aromatic heterocycles, which have been arranged into 11 subgroups in order to facilitate comparisons of the data sets between the groups. This division was done on the basis of degree of aromaticity and according to the presence of other heteroatoms (i.e. nitrogen). SUMMARYTwelve flavouring substances possess one or more chiral centres. For four of these substances 15.057, 15.079 and 15.135] the stereoisomeric composition has not been specified sufficiently.Forty-six of the flavouring substances are classified into structural class II and 13 candidate substances are classified into structural class III, according to the decision tree approach presented by Cramer et al., 1978. Forty-four candidate substances in the present group have been reported to occur in a wide range of food items.In its evaluation, the Panel as a default used the "Maximised Survey-derived Daily Intake" (MSDI) approach to estimate the per capita intakes of the flavouring substances in Europe. However, when the Panel examined the information provided by the European Flavour Industry on the use levels in various foods, it appeared obvious that the MSDI approach in a number of cases would grossly underestimate th...

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Section: ])contrasting

confidence: 55%

“…The final metabolite is subsequently excreted via urine, and may be converted spontaneously into 2-thienylmercapturic acid (Dansette et al, 1992). The authors considered the formation of the epoxide intermediate, as suggested by Bray et al (1971), highly unlikely.…”

Section: ])mentioning

confidence: 99%

Scientific Opinion on Flavouring Group Evaluation 21, Revision 3 (FGE.21Rev3): Thiazoles, thiophenes, thiazoline and thienyl derivatives from chemical groups 29 and 30

Flavourings¹

2012

EFSA Journal

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“…More than 70 % of thiophene administered to rats by gavage (200-300 mg/kg b.w.) was excreted in expired air and in urine within 24 h (Bray et al, 1971), suggesting that the major part of this compound was absorbed through the gastrointestinal tract.…”

Section: Sulphur-containing Moahmentioning

confidence: 99%

“…Sulphur-containing aromatic compounds Bray et al (1971) found that thiophene (200-300 mg/kg b.w.) administered by gavage to rats was partly (approximately 30 % of the dose) excreted unchanged in expired air and partly (approximately 40 % of the dose) eliminated as mercapturic acids in urine.…”

Section: Moahmentioning

confidence: 99%

Scientific Opinion on Mineral Oil Hydrocarbons in Food

2012

EFS2

107

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Consumers are exposed to a range of mineral oil hydrocarbons (MOH) via food. Mineral oil saturated hydrocarbons (MOSH) consist of linear and branched alkanes, and alkyl-substituted cyclo-alkanes, whilst mineral oil aromatic hydrocarbons (MOAH) include mainly alkyl-substituted polyaromatic hydrocarbons. Products, commonly specified according to their physico-chemical properties, may differ in chemical composition depending on the oil source. Technical grade MOH contain 15 -35 % MOAH, which is minimised in food grade MOSH (white oils). Major sources of MOH in food are food packaging and additives, processing aids, and lubricants. Estimated MOSH exposure ranged from 0.03 to 0.3 mg/kg b.w. per day, with higher exposure in children. Specific production practices of bread and grains may provide additional MOSH exposure. Except for white oils, exposure to MOAH is about 20 % of that of MOSH. Absorption of alkanes with carbon number above C 35 is negligible. Branched and cyclic alkanes are less efficiently oxidised than n-alkanes. MOSH from C 16 to C 35 may accumulate and cause microgranulomas in several tissues including lymph nodes, spleen and liver. Hepatic microgranulomas associated with inflammation in Fischer 344 rats were considered the critical effect. The no-observed-adverse-effect level for induction of liver microgranulomas by the most potent MOSH, 19 mg/kg b.w. per day, was used as a Reference Point for calculating margins of exposure (MOEs) for background MOSH exposure. MOEs ranged from 59 to 680. Hence, background exposure to MOSH via food in 1 On request from the European Commission, Question No EFSA-Q-2010-00170, adopted on 3 May 2012. 2 SUMMARYFollowing a request from the European Commission, the EFSA Panel on Contaminants in the Food Chain (CONTAM Panel) was asked to deliver a scientific opinion on mineral oil hydrocarbons (MOH) in Food. Mineral oil hydrocarbons occur in food both as a result of contamination and from various intentional uses in food production. In order to assess the need for possible regulatory measures as regards MOH in food, EFSA was requested to assess the risks related to their occurrence in food. More specifically, the opinion should evaluate whether new toxicity data are available and whether the current acceptable daily intakes (ADIs) are still applicable, explore whether certain classes (or subclasses) of MOH are more relevant due to their toxicity or to differences in the way they are metabolised by the human body, and identify the different background sources, other than from adulteration or misuse, of MOH occurrence in food. In addition a dietary exposure assessment was requested for the general population and for specific subgroups of the population (e.g. infants, children and people following specific diets), by taking into account the background occurrence of MOH in food. Included in the request was also to advise on MOH and food classes to be included if monitoring were to be set up for their presence in food.The scientific literature and other sources were s...

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“…Rabbit ( Other urinary metabolites, in particular conjugates of 2-hydroxy-or 3-hydroxythiophene, any acidhydrolysable products of thiophene or free thiophene were not found (Bray et al, 1971). …”

Section: Metabolitesmentioning

confidence: 99%

Scientific Opinion on Flavouring Group Evaluation 21, Revision 2 (FGE.21Rev2): Thiazoles, thiophene, thiazoline and thienyl derivatives from chemical group 29. Miscellaneous substances from chemical group 30

Flavourings¹

2011

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 evaluate 56 flavouring substances in the Flavouring Group Evaluation 21, Revision 2, using the Procedure in Commission Regulation (EC) No 1565/2000. Seven of the substances 15.086, 15.090, 15.099, 15.114, 15.119 and 15.133] were considered to have genotoxic potential. The remaining 49 substances were evaluated through a stepwise approach (the Procedure) that integrates information on structure-activity relationships, intake from current uses, toxicological threshold of concern, and available data on metabolism and toxicity. The Panel concluded that 26 substances 15.039, 15.044, 15.050, 15.051, 15.052, 15.058, 15.061, 15.062, 15.063, 15.067, 15.068, 15.069, 15.071, 15.078, 15.080, 15.082, 15.084, 15.085, 15.087, 15.089, 15.098, 15.108, 15.115, 15.116 and 15.118] do not give rise to safety concerns at their levels of dietary intake, estimated on the basis of the MSDI approach. For the remaining 23 candidate substances 15.040, 15.042, 15.043, 15.045, 15.054, 15.055, 15.064, 15.070, 15.072, 15.074, 15.076, 15.077, 15.088, 15.091, 15.092, 15.093, 15.094, 15.096, 15.097, 15.106, 15.107 and 15.129], of the 49 substances evaluated through the Procedure, no appropriate NOAEL was available and additional data are required. Besides the safety assessment of these flavouring substances, the Flavouring Group Evaluation 21, Revision 2 2 EFSA Journal 2011; 9(10):1989 specifications for the materials of commerce have also been considered. For two substances are an identity test lacking and for one has the stereoisomeric composition to be specified. In the present FGE.21Rev2, the 56 candidate substances include five-and six-membered sulphurcontaining aromatic and non-aromatic heterocycles, which have been arranged into 11 subgroups in order to facilitate comparisons of the data sets between the groups. This division was done on the basis of degree of aromaticity and according to the presence of other heteroatoms (i.e. nitrogen).Five of the 56 candidate substances possess one chiral centre Forty-six of the 56 candidate substances are classified into structural class II and 10 candidate substances are classified into structural class III, according to the decision tree approach presented by Cramer et al., 1978. Forty-two of 56 the candidate substances have been reported to occur in a wide range of food items.In its evaluation, the Panel as a default used the "Maximised Survey-derived Daily Intake" (MSDI) approach to estimate the per capita intakes of the flavouring substances in Europe. However, when the Panel examined the information provided by the European Flavour Industry on the use levels in various foods, it appeared obvious that the MSDI approach in a number of cases would grossly underestimate the intake by regular consumers of products flavoured at the use level reported by the Industry, especially in those cases where the annual production values were reported to be small. ...

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The Metabolism of Thiophen in the Rabbit and the Rat

Cited by 37 publications

References 38 publications

Scientific Opinion on Flavouring Group Evaluation 21, Revision 3 (FGE.21Rev3): Thiazoles, thiophenes, thiazoline and thienyl derivatives from chemical groups 29 and 30

Scientific Opinion on Flavouring Group Evaluation 21, Revision 3 (FGE.21Rev3): Thiazoles, thiophenes, thiazoline and thienyl derivatives from chemical groups 29 and 30

Scientific Opinion on Mineral Oil Hydrocarbons in Food

Scientific Opinion on Flavouring Group Evaluation 21, Revision 2 (FGE.21Rev2): Thiazoles, thiophene, thiazoline and thienyl derivatives from chemical group 29. Miscellaneous substances from chemical group 30

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