Toxicological tests on flavouring matters. II. Pyrazines and other compounds

Posternak, J; Dufour, J. J.; Rogg, C.; Vodoz, C.A.

doi:10.1016/s0015-6264(75)80215-x

Cited by 38 publications

(30 citation statements)

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“…90 Food consumption and body weights were recorded weekly, and hematological examinations and blood urea nitrogen measurements were performed on half of the animals at 7 weeks and on the remaining animals at 13 weeks. A slight nonstatistical increase in blood urea nitrogen was observed at the end of the study.…”

Section: International Journal Of Toxicology 33(supplement 1)mentioning

confidence: 99%

Disulfide Oil Hazard Assessment Using Categorical Analysis and a Mode of Action Determination

Morgott

Bootman²,

Banton

2013

Int J Toxicol

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Diethyl and diphenyl disulfides, naphtha sweetening (Chemical Abstracts Service [CAS] # 68955-96-4), are primarily composed of low-molecular-weight dialkyl disulfides extracted from C 4 to C 5 light hydrocarbon streams during the refining of crude oil. The substance, commonly known as disulfide oil (DSO), can be composed of up to 17 different disulfides and trisulfides with monoalkyl chain lengths no greater than C 4 . The disulfides in DSO constitute a homologous series of chemical constituents that are perfectly suited for a hazard evaluation using a read-across/worst-case approach. The DSO constituents exhibit a common mode of action that is operable at all trophic levels. The observed oxidative stress response is mediated by reactive oxygen species and free radical intermediates generated after disulfide bond cleavage and subsequent redox cycling of the resulting mercaptan. Evidence indicates that the lowest series member, dimethyl disulfide (DMDS), can operate as a worst-case surrogate for other members of the series, since it displays the highest toxicity. Increasing the alkyl chain length or degree of substitution has been shown to serially reduce disulfide toxicity through resonance stabilization of the radical intermediate or steric inhibition of the initial enzymatic step. The following case study examines the mode of action for dialkyl disulfide toxicity and documents the use of read-across information from DMDS to assess the hazards of DSO. The results indicate that DSO possesses high aquatic toxicity, moderate environmental persistence, low to moderate acute toxicity, high repeated dose toxicity, and a low potential for genotoxicity, carcinogenicity, and reproductive/developmental effects.

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Section: International Journal Of Toxicology 33(supplement 1)mentioning

confidence: 99%

Disulfide Oil Hazard Assessment Using Categorical Analysis and a Mode of Action Determination

Morgott

Bootman²,

Banton

2013

Int J Toxicol

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“…(Posternak et al, 1975) Toxicity data reported as part of a summary publication on a large number of flavouring substances. Body weight, food utilisation, haematological and histopathology examination undertaken, clinical chemistry restricted to blood urea nitrogen, organ weight changes restricted to liver and kidney.…”

Section: Rat; M/fmentioning

confidence: 99%

Scientific Opinion on Flavouring Group Evaluation 21, Revision 5 (FGE.21Rev5): Thiazoles, thiophenes, thiazoline and thienyl derivatives from chemical groups 29 and 30

Flavourings¹

2015

EFS2

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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 41 flavouring substances in Flavouring Group Evaluation 21, Revision 5, using the Procedure in Commission Regulation (EC) No 1565/2000. This revision was carried out because of the inclusion of the assessment of new toxicity data on the candidate substances, 5-ethylthiophene-2-carbaldehyde .074] and 2-pentylthiophene . These data on 5-ethylthiophene-2-carbaldehyde .074] should cover 2-acetylthiophene .040] and 2-propionylthiophene . These data on 2-pentylthiophene .096] should cover 2-butylthiophene .045], 2-hexylthiophene .076] and 2-octylthiophene . For two of the substances ] the Panel concluded that additional genotoxicity data are required. The remaining 39 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 the 39 flavouring substances 15.039, 15.040, 15.044, 15.045, 15.050, 15.051, 15.052, 15.054, 15.055, 15.057, 15.058, 15.061, 15.062, 15.063, 15.067, 15.068, 15.069, 15.071, 15.074, 15.076, 15.078, 15.079, 15.080, 15.082, 15.084, 15.085, 15.086, 15.087, 15.089, 15.093, 15.096, 15.097, 15.098, 15.108, 15.115, 15.116, 15.118 and 15.135] do not give rise to safety concerns at their levels of dietary intake, estimated on the basis of the Maximised Survey-derived Daily Intake (MSDI) approach. Besides the safety assessment of these flavouring substances, the specifications for the materials of commerce have also been considered. Adequate specifications, including complete purity criteria and identity for the materials of commerce, have been provided for all 41 candidate substances. All candidate substances are five-or six-member sulphur-containing heterocyclic compounds, some of which also contain nitrogen. They have been divided into two main groups: (A) those with an aromatic ring (33 candidate substances) and (B) those with a non-aromatic ring structure (8 candidate substances). All are ring-substituted with one or more of the substituents alkyl, alkenyl, aryl, alcohol, keto and thio. For assessment purposes, the following further subdivision of groups (A) and (B) has been made:-(Subgroup A-Ia: Thiophene. The substance previously allocated to the group is no longer supported for use as a flavouring substance in Europe by Industry.)-Subgroup A-Ib: Thiophene derivatives with non-thiol-containing ring substituents.-Subgroup A-Ic: Thiophene derivatives with thiol-containing ring substituents.-Subgroup A-II: Thiazole derivatives.-(Subgroup A-III: Benzothiazoles. The substance previously allocated to the group is no longer supported for use as flavouring substance in Europe by Industry.)• Group (B): Non-aromatic:-(Subgroup B-I: Dihydrothiophenes. The substance previously allocated to the group is no longer supported for use as a flavouring substance...

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“…For the substance 2-methyl-5-methoxythiazole .002], an NOAEL of 8.6 mg/kg bw/day was identified from a 90-day toxicity study (Posternak et al, 1975 For the substance 2-thienyl disulphide .008], an NOAEL of 0.29 mg/kg bw/day was identified from a 90-day toxicity study (Morgareidge and Oser, 1970g Therefore the Panel concluded at step B4 of the Procedure that these three substances would be of no safety concern at their estimated levels of intake based on the MSDI approach. For the remaining 16 substances the Panel, in contrast to the JECFA, did not anticipate that they will be metabolised to innocuous products due to concern with respect to N-oxidation of pyridines and for the pyrroles concerns about N-oxidation and epoxidation and accordingly concluded that they should be evaluated along the B-side.…”

Section: Fge75 Tetrahydrofuran and Furanone Derivatives (Efsa 2008aw)mentioning

confidence: 99%

Scientific Opinion on Flavouring Group Evaluation 96 (FGE.96): Consideration of 88 flavouring substances considered by EFSA for which EU production volumes / anticipated production volumes have been submitted on request by DG SANCO. Addendum to FGE. 51, 5

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 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 FGE.96 concerns 88 JECFA-evaluated substances from different FGEs. Common for all the 88 substances was that for none of them European production volumes were available at the time for the first consideration of the FGEs in question. As a consequence, no MSDI could be calculated for EU and accordingly the substances could not be considered by EFSA using the evaluation Procedure. Industry has now provided production volumes for these substances. Based on these newly provided production figures, MSDI values for EU have been calculated and based on these MSDI values the substances have been re-considered by the 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. In the FGEs in question, genotoxicity of the substances considered in FGE.96 has already been addressed. For none of the substances a concern for genotoxicity was identified. The Panel concluded that 87 of the substances do not give rise to safety concerns at the levels of dietary intake, estimated on the basis of the MSDI approach. However, for the substance 2-acetyl-1-ethylpyrrole .045], the Panel could not identify an appropriate NOAEL and accordingly additional data are required. Besides the safety assessment of these flavouring substances, the specifications for the materials of commerce have also been considered and for eight stereoisomeric substances 08.073, 09.371, 09.780, 10.050, 13.060, 13.161 and 16.039], the stereoisomeric composition has to be specified further.

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Toxicological tests on flavouring matters. II. Pyrazines and other compounds

Cited by 38 publications

References 0 publications

Disulfide Oil Hazard Assessment Using Categorical Analysis and a Mode of Action Determination

Disulfide Oil Hazard Assessment Using Categorical Analysis and a Mode of Action Determination

Scientific Opinion on Flavouring Group Evaluation 21, Revision 5 (FGE.21Rev5): Thiazoles, thiophenes, thiazoline and thienyl derivatives from chemical groups 29 and 30

Scientific Opinion on Flavouring Group Evaluation 96 (FGE.96): Consideration of 88 flavouring substances considered by EFSA for which EU production volumes / anticipated production volumes have been submitted on request by DG SANCO. Addendum to FGE. 51, 5

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