title: The Japan Flavour and Fragrance Materials Association's (JFFMA) safety assessment of acetal food flavouring substances uniquely used in Japan.
abstract: 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.
authors.affiliation: a Japan Flavour and Fragrance Materials Association (JFFMA) , Tokyo , Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Okamura
authors.forename: Hajime
authors.initials: H
authors.lastname: Abe
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Hasegawa-Baba
authors.forename: Kenji
authors.initials: K
authors.lastname: Saito
authors.forename: Fumiko
authors.initials: F
authors.lastname: Sekiya
authors.forename: Shim-Mo
authors.initials: SM
authors.lastname: Hayashi
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Mirokuji
authors.forename: Shinpei
authors.initials: S
authors.lastname: Maruyama
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ono
authors.forename: Madoka
authors.initials: M
authors.lastname: Nakajima
authors.forename: Masakuni
authors.initials: M
authors.lastname: Degawa
authors.forename: Shogo
authors.initials: S
authors.lastname: Ozawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Shibutani
authors.forename: Tamio
authors.initials: T
authors.lastname: Maitani
mesh_terms: D005421:Flavoring Agents / Q000009:adverse effects* / Q000737:chemistry; D005503:Food Additives / Q000009:adverse effects* / Q000737:chemistry; D064088:Hazard Analysis and Critical Control Points; D006801:Humans; D007564:Japan; D015394:Molecular Structure
chemical_list: D005421:Flavoring Agents; D005503:Food Additives
keywords: Cramer’s decision tree; Joint FAO/WHO Expert Committee on Food Additives (JECFA); acetals; food flavours; safety; threshold of toxicological concern (TTC)