Dietary administration of β-ionone epoxide to Sprague-Dawley rats for 90 days

Vivian Lu; Maria Bastaki; Anne Marie Api; Michel Aubanel; Mark Bauter; Thierry Cachet; Jan Demyttenaere; Maodo Malick Diop; Christie L Harman; Shim-Mo Hayashi; Gerhard Krammer; Odete Mendes; Kevin J Renskers; Jürgen Schnabel; Sean V Taylor

doi:10.1016/j.crtox.2021.05.001

Dietary administration of β-ionone epoxide to Sprague-Dawley rats for 90 days

Curr Res Toxicol. 2021 May 18:2:192-201. doi: 10.1016/j.crtox.2021.05.001. eCollection 2021.

Authors

Affiliations

¹ International Organization of the Flavor Industry, 1101 17th Street NW, Suite 700, Washington, DC 20036, USA.
² Research Institute for Fragrance Materials, Inc., 50 Tice Blvd., Woodcliff Lake, NJ 07677, USA.
³ Kerry Flavours France, Zl du Plan BP 82067, 63 Avenue Jean Maubert, 06131 Grasse Cedex, France.
⁴ Product Safety Labs, 2394 US Route 130, Dayton, NJ 08810, USA.
⁵ International Organization of the Flavor Industry, Avenue des Arts 6, B-1210 Brussels, Belgium.
⁶ European Flavour Association, Avenue des Arts 6, B-1210 Brussels, Belgium.
⁷ V. Mane Fils, 620 Route de Grasse, 06620 Le Bar-sur-Loup, France.
⁸ Flavor and Extract Manufacturers Association, 1101 17th Street NW, Suite 700, Washington, DC 20036, USA.
⁹ Japan Flavor and Fragrance Materials Association, Sankeinihonbashi Bldg. 6F, 4-7-1 Nihonbashi-Honcho, Chuo-ku, Tokyo, 103-0023, Japan.
¹⁰ Symrise AG, Muhlenfeldstrasse 1, 37603 Holzminden, Germany.
¹¹ Takasago International Corporation, 4 Volvo Drive, PO Box 932, Rockleigh, NJ 07647, USA.
¹² Givaudan International SA, Kemptpark 50, 8310 Kemptthal, Switzerland.

Abstract

In a 90-day GLP-compliant study groups of Sprague-Dawley rats (10/sex/group) were fed diets containing β-ionone epoxide, a fragrance material and a flavoring substance, at dietary concentrations providing target intakes of 0, 20, 40 and 80 mg/kg bw/day. There were no deaths and no adverse changes in clinical observations, ophthalmological examinations, body weight, body weight gain, food consumption, food efficiency; hematology, serum chemistry, urinalysis parameters; or in macroscopic findings attributable to β-ionone epoxide administration. Increased absolute and relative liver weights in high dose females without correlating hepatic histopathological findings were considered non-adverse. Cortical vacuolation of adrenal zona fasciculata was observed in high-dose males but was considered non-adverse due to the nondegenerative nature of this alteration. β-Ionone epoxide did not influence estrus cyclicity in females and did not affect sperm morphology or epididymal sperm count, homogenization-resistant spermatid count and motility measurements in male rats. The no-observed-adverse-effect level (NOAEL) for administration of β-ionone epoxide in the diet was determined to be the highest dose tested of 80 mg/kg bw/day.

Keywords: AAALAC, Association for Assessment and Accreditation of Laboratory Animal Care; CAS, Chemical Abstracts Service; CFR, Code of Federal Regulation; EFSA, European Food Safety Authority; EPA, Environmental Protection Agency; FDA, Food and Drug Administration; FEMA GRAS; FEMA, Flavor and Extract Manufacturers Association; GLP, Good Laboratory Practice; GRAS, Generally Recognized as Safe; JECFA, Joint FAO/WHO Expert Committee on Food Additives; MW, molecular weight; NOAEL, no-observed-adverse-effect level; OECD, Organisation of Economic Cooperation and Development; RSD, relative standard deviation; Rat; SD, standard deviation; Toxicity; beta-Ionone epoxide; bw or BdW, body weight; flavoring ingredient; fragrance material; ppm, parts per million.