Extended one-generation reproductive toxicity study evaluating gardenia blue in Sprague Dawley rats

Melanie L Foster; Debabrata Mahapatra; Robert R Maronpot; Masayuki Nishino; Shuichi Chiba; Mihoko Koyanagi; Florence Burleson; Shim-Mo Hayashi

doi:10.1016/j.yrtph.2023.105472

Extended one-generation reproductive toxicity study evaluating gardenia blue in Sprague Dawley rats

Regul Toxicol Pharmacol. 2023 Oct:144:105472. doi: 10.1016/j.yrtph.2023.105472. Epub 2023 Aug 21.

Authors

Melanie L Foster¹, Debabrata Mahapatra², Robert R Maronpot³, Masayuki Nishino⁴, Shuichi Chiba⁴, Mihoko Koyanagi⁴, Florence Burleson⁵, Shim-Mo Hayashi⁶

Affiliations

¹ Integrated Laboratory Systems LLC, An Inotiv Company, 601 Keystone Park Drive, Suite 200, Morrisville, NC, 27560, USA. Electronic address: melanie.foster@inotivco.com.
² Integrated Laboratory Systems LLC, An Inotiv Company, 601 Keystone Park Drive, Suite 200, Morrisville, NC, 27560, USA.
³ Maronpot Consulting LLC, 1612 Medfield Road, Raleigh, NC, 27607, USA.
⁴ San-Ei Gen, F.F.I., Inc., 1-1-11, Sanwa-cho, Toyonaka, Osaka, 561-8588, Japan.
⁵ Burleson Research Technologies, Inc., 120 First Flight Lane, Morrisville, NC, 27560, USA.
⁶ Tokyo University of Agriculture and Technology, Tokyo, 183-8509, Japan; National Institute of Health Sciences, Kawasaki, Kanagawa, 210-9501, Japan.

PMID: 37611796
DOI: 10.1016/j.yrtph.2023.105472

Abstract

Gardenia blue powder was administered at 0.5%, 2.5%, or 5.0% in feed to male and female Sprague Dawley rats in an Extended One-Generation Reproductive Toxicity Study (OECD Test Guideline 443). The dosed diet began 14 days before mating and was continued at the same concentration level for the entire study for all parental animals (P₀) and offspring (F₁). At weaning, offspring were allocated into one of 5 cohorts for different endpoints. P₀ and F₁ animals had blue urine, blue or black feces, and blue discolorations in gastrointestinal organs, mesenteric lymph nodes, and kidneys. This treatment-related finding was not considered adverse as there were no histopathologic correlates. There was a dose-related increase in sperm concentration in P₀ and F₁ males. There were dose-related increases in heart weights of F₁ postnatal day (PND) 21 males, male and female thyroid weights, and female TSH levels of PND 91 F₁ offspring, with no histopathological correlate. There were no consistent treatment-related adverse effects on any other parameters evaluated for general toxicity, reproductive toxicity, developmental neurotoxicity, or developmental immunotoxicity. The highest dietary concentration (5.0%) of gardenia blue powder was the no observed adverse effect level (NOAEL) for male and female rats at all life stages evaluated.

Keywords: Developmental; Extended one-generation; Food additive; Food colorant; Gardenia blue; Immunotoxicity; Neurotoxicity; Reproductive; Safety assessment.