Prenatal developmental toxicity of gardenia blue, a natural food colorant, in rats and rabbits

Gardenia blue is a colorant widely used in Asia in food and beverages. The objectives of the present studies were to evaluate the maternal and prenatal embryo-fetal developmental toxicity of gardenia blue in rats and rabbits. Sprague Dawley rats and New Zealand White rabbits were administered gardenia blue daily by oral gavage at doses of 0 (deionized water vehicle), 500, 1000 or 2000 mg/kg/day on Gestation Days 6 through 20 (rats) and 7 through 28 (rabbits). Endpoints evaluated included clinical observations, body weight, food consumption, thyroid hormones (rats), thyroid weights and histopathology (rats), gross pathologic changes, ovarian and uterine observations, fetal weight and anogenital distance (rats) and fetal morphology (external, visceral and skeletal). Treatment related maternal findings attributed to the blue/dark color of the test substance included body surface staining, and dark/blue discoloration of the kidneys, gastrointestinal track and mesenteric lymph nodes at all or most doses in the rat and/or rabbit. Slight reductions in food consumption without effects on body weight were also observed in rats at all doses and in rabbits at 2000 mg/kg/day. There were no treatment related effects on maintenance of pregnancy, postimplantation loss, litter size, fetal weight and anogenital distance, or fetal external, visceral, or skeletal malformations and variations. Based on these results, the maternal and developmental no-observed-adverse-effect level for gardenia blue in rats and rabbits was ≥2000 mg/kg/day.

[1]  Byungkyung Do,et al.  Genotoxicity test of eight natural color additives in the Korean market , 2022, Genes and environment : the official journal of the Japanese Environmental Mutagen Society.

[2]  R. Maronpot,et al.  Genotoxicity evaluation of the naturally-derived food colorant, gardenia blue, and its precursor, genipin. , 2018, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[3]  Test No. 414: Prenatal Developmental Toxicity Study , 2018, OECD Guidelines for the Testing of Chemicals, Section 4.

[4]  K. Chiba,et al.  Neuroprotective action of genipin on tunicamycin-induced cytotoxicity in neuro2a cells. , 2009, Biological & pharmaceutical bulletin.

[5]  E. Park,et al.  Anti-inflammatory evaluation of gardenia extract, geniposide and genipin. , 2006, Journal of ethnopharmacology.

[6]  Y. Song,et al.  Antiinflammatory effects of genipin, an active principle of gardenia. , 2004, European journal of pharmacology.

[7]  K. Chiba,et al.  Prevention of the Neurotoxicity of the Amyloid β Protein by Genipin , 2001 .

[8]  Y. Ikeda,et al.  Antithrombotic Effect of Geniposide and Genipin in the Mouse Thrombosis Model , 2001, Planta medica.

[9]  J. L. Stuckhardt,et al.  Fresh visceral examination of rat and rabbit fetuses used in teratogenicity testing. , 1984, Teratogenesis, carcinogenesis, and mutagenesis.

[10]  D. Woo,et al.  "Apparent hydronephrosis" as a normal aspect of renal development in late gestation of rats: the effect of methyl salicylate. , 1972, Teratology.

[11]  James G. Wilson,et al.  EMBRYOLOGICAL CONSIDERATIONS IN TERATOLOGY * , 1965, Annals of the New York Academy of Sciences.

[12]  A. B. Dawson A Note on the Staining of the Skeleton of Cleared Specimens with Alizarin Red S , 1926 .