The genetic toxicology of some hydrocarban and oxygenated solvents

Brooks, T.M.; Meyer, Amy; Hutson, D. H.

doi:10.1093/mutage/3.3.227

Cited by 52 publications

(15 citation statements)

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“…The only fetal effects in developmental toxicity studies were developmental delays at maternally toxic levels (Daughtrey et al 1994a, Johnson et al 2012, Kreckmann et al 2000, and reproductive toxicity tests provided no evidence of impairment of fertility , Daughtrey et al 1994a, Kreckmann et al 2000, Yu et al 2011. These solvents are not active in tests for mutagenic activity (Brooks et al 1988, Daughtrey et al 1994b, Galvin and Marashi 1999a, 1999b, 1999c, Kirwin et al 1980, 1991, Loury et al 1986, McCarroll et al 1981a, 1981b, Mortelmans et al 1986, Richardson et al 1986). Chronic exposure to commercial hexane resulted in an increase in liver tumors in female mice, but it did not increase the frequency of tumors in male mice or in rats of either gender (Daughtrey et al 1999).…”

Section: Light Aliphatic Solvents (C5-c9)mentioning

confidence: 98%

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Characterization of the toxicological hazards of hydrocarbon solvents

McKee

Adenuga

Carrillo

2015

Critical Reviews in Toxicology

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Hydrocarbon solvents are liquid hydrocarbon fractions derived from petroleum processing streams, containing only carbon and hydrogen atoms, with carbon numbers ranging from approximately C5-C20 and boiling between approximately 35-370°C. Many of the hydrocarbon solvents have complex and variable compositions with constituents of 4 types, alkanes (normal paraffins, isoparaffins, and cycloparaffins) and aromatics (primarily alkylated one-and tworing species). Because of the compositional complexity, hydrocarbon solvents are now identified by a nomenclature ("the naming convention") that describes them in terms of physical/ chemical properties and compositional elements. Despite the compositional complexity, most hydrocarbon solvent constituents have similar toxicological properties, and the overall toxicological hazards can be characterized in generic terms. To facilitate hazard characterization, the solvents were divided into 9 groups (categories) of substances with similar physical and chemical properties. Hydrocarbon solvents can cause chemical pneumonitis if aspirated into the lung, and those that are volatile can cause acute CNS effects and/or ocular and respiratory irritation at exposure levels exceeding occupational recommendations. Otherwise, there are few toxicologically important effects. The exceptions, n-hexane and naphthalene, have unique toxicological properties, and those solvents containing constituents for which classification is required under the Globally Harmonized System (GHS) are differentiated by the substance names. Toxicological information from studies of representative substances was used to fulfill REACH registration requirements and to satisfy the needs of the OECD High Production Volume (HPV) initiative. As shown in the examples provided, the hazard characterization data can be used for hazard classification and for occupational exposure limit recommendations. Introduction Scope and purpose of the documentThe present document summarizes information on the physical/ chemical properties and toxicological hazards of hydrocarbon solvents and provides examples of the ways in which the information on hazard characterization can be used for hazard classification and to set occupational exposure limits. Many of the toxicological studies were published separately, but the results are summarized herein and referenced in the appendices.Hydrocarbon solvents are liquid hydrocarbon fractions that are primarily produced by the distillation of petroleum feed stocks or their synthetic analogs (e.g., Fischer-Tropsch derived materials), sometimes followed by additional processing steps such as solvent extraction, hydrodesulfurization, or hydrogenation. 1 Most hydrocarbon solvents are complex substances with variable compositions and are best described as UVCB 2 (unknown and variable composition) substances, but some are single constituent (mono-constituent) substances. The complex and variable nature of these solvents is the consequence of their manufacturing processes. In short, most hydroca...

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Section: Light Aliphatic Solvents (C5-c9)mentioning

confidence: 98%

“…A comprehensive in vitro evaluation of the mutagenic potential of n-heptane was published by Brooks et al (1988). More specifically, n-heptane was tested for mutation in Salmonella and E. coli, gene conversion in Saccharomyces cerevisiae, and for chromosomal aberrations in rat liver cells (RL4) in culture.…”

Section: Genetic Toxicitymentioning

confidence: 99%

Characterization of the toxicological hazards of hydrocarbon solvents

McKee

Adenuga

Carrillo

2015

Critical Reviews in Toxicology

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“…Several in vivo and in vitro genotoxicity studies of acetaldehyde, hexanal, acetoin, hexanal, butyl alcohol and 4-methyl 2-pentanon, which are components of acetals, have been reported (Brambrilla et al 1989;Brooks et al 1988;Dillon et al 1992;Florin et al 1980;FSCJ 2005b;Furnus et al 1990;Garst et al 1983;He and Lambert 1985;Helander and Lindahl-Kiessling 1991;Kapp et al 1993;Kim et al 1987;Marnett et al 1985;Martelli et al 1994;Muller et al 1993;Norppa et al 1985;Obe and Ristow 1977;O'Donoghue et al 1988;Wangenheim and Bolcsfoldi 1998;WHO 1998;Zeiger et al 1992). The results of these studies are summarized in Table 6.…”

Section: Genotoxicitymentioning

confidence: 99%

The Japan Flavour and Fragrance Materials Association’s (JFFMA) safety assessment of acetal food flavouring substances uniquely used in Japan

Okamura¹,

Abe

Hasegawa-Baba

et al. 2015

Food Additives & Contaminants: Part A

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Using the procedure devised by the Joint FAO/WHO Expert Committee on Food Additives (JECFA), we performed safety evaluations on five acetal flavouring substances uniquely used in Japan: acetaldehyde 2,3-butanediol acetal, acetoin dimethyl acetal, hexanal dibutyl acetal, hexanal glyceryl acetal and 4-methyl-2-pentanone propyleneglycol acetal. As no genotoxicity study data were available in the literature, all five substances had no chemical structural alerts predicting genotoxicity. Using Cramer's classification, acetoin dimethyl acetal and hexanal dibutyl acetal were categorised as class I, and acetaldehyde 2,3-butanediol acetal, hexanal glyceryl acetal and 4-methyl-2-pentanone propyleneglycol acetal as class III. The estimated daily intakes for all five substances were within the range of 1.45-6.53 µg/person/day using the method of maximised survey-derived intake based on the annual production data in Japan from 2001, 2005, 2008 and 2010, and 156-720 µg/person/day using the single-portion exposure technique (SPET), based on the average use levels in standard portion sizes of flavoured foods. The daily intakes of the two class I substances were below the threshold of toxicological concern (TTC) - 1800 μg/person/day. The daily intakes of the three class III substances exceeded the TTC (90 μg/person/day). Two of these, acetaldehyde 2,3-butanediol acetal and hexanal glyceryl acetal, were expected to be metabolised into endogenous products after ingestion. For 4-methyl-2-pentanone propyleneglycol acetal, one of its metabolites was not expected to be metabolised into endogenous products. However, its daily intake level, based on the estimated intake calculated by the SPET method, was about 1/15 000th of the no observed effect level. It was thus concluded that all five substances raised no safety concerns when used for flavouring foods at the currently estimated intake levels. While no information on in vitro and in vivo toxicity for all five substances was available, their metabolites were judged as raising no safety concerns at the current levels of intake.

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“…The NOAEL is probably higher than the reported dose level that produced no adverse effects. (Brooks et al, 1988) Published study summarising an extended industry report. Study is considered valid.…”

Section: Conclusion On Genotoxicitymentioning

confidence: 99%

Scientific Opinion on Flavouring Group Evaluation 11, Revision 3 (FGE.11Rev3): Aliphatic dialcohols, diketones, and hydroxyketones from chemical groups 8 and 10

Flavourings¹

2014

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 11 flavouring substances in the Flavouring Group Evaluation 11, Revision 3, using the Procedure in Commission Regulation (EC) No 1565/2000. The 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 present Revision of FGE.11, FGE.11Rev3, is prepared due to the evaluation of genotoxicity data, which have been requested in the previous version of FGE.11, for 3-methylnona-2,4-dione . Additionally, new information on the stereoisomerism of has become available. Based on the new data received the Panel concluded that all 11 flavouring substances 07.071, 07.097, 07.152, 07.165, 07.167, 07.168, 07.184, 07.238, 07.248 and 07.260] do not give rise to safety concerns at their levels of dietary intake, estimated on the basis of the MSDI approach. Besides the safety assessment of these flavouring substances, the specifications for the materials of commerce have also been considered. Specifications including complete purity criteria and identity for the materials of commerce have been provided for all candidate substances. . For all substances, the stereoisomeric composition has been specified sufficiently. © EuropeanFive of the flavouring substances are classified in structural class I, five in structural class II and one in structural class III.Nine of the flavouring substances in the present group have been reported to occur naturally 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. In consequence, the Panel had reservations about the data on use and use levels provided and the intake estimates obtained by the MSDI approach.In the absence of more precise information that would enable the Panel to make a more realistic estimate of the intakes of the flavouring substances, the Panel has decided also to perform an estimate of the daily intakes per person using a "modified Theoretical Added Maximum Daily Intake" (mTAMDI) approach based on the normal use levels reported by Industry. In those cases where the mTAMDI approach indicated that the intake of a flavouring substance might exceed its corresponding threshold of concern, the Panel decided not to carry out a formal safety assessment using the Procedure. In these cases the Pane...

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The genetic toxicology of some hydrocarban and oxygenated solvents

Cited by 52 publications

References 0 publications

Characterization of the toxicological hazards of hydrocarbon solvents

Characterization of the toxicological hazards of hydrocarbon solvents

The Japan Flavour and Fragrance Materials Association’s (JFFMA) safety assessment of acetal food flavouring substances uniquely used in Japan

Scientific Opinion on Flavouring Group Evaluation 11, Revision 3 (FGE.11Rev3): Aliphatic dialcohols, diketones, and hydroxyketones from chemical groups 8 and 10

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