Safety of a Novel Calcium/Potassium Saltof (-)-Hydroxycitric Acid (HCA-SX): II.Developmental Toxicity Study in Rats

ABSTRACT

(-)-Hydroxycitric acid (HCA), active constituent (10%–30%) of the dried fruit rind of Garcinia cambogia, is commonly used as a dietary supplement for weight management. The objective of the present study was to evaluate the teratogenic potential of a novel calcium/potassium salt of HCA (HCA-SX) in Sprague-Dawley rats. Due to its potential to affect fat synthesis and reduce food intake, processes that are often crucial in normal fetal development, this teratology study was undertaken as part of a multigeneration reproductive investigation. The animals in this study were selected randomly after weaning from each F_2b litter of the F₁ generation from the two-generation reproductive toxicity study. To start the teratology study, Sprague-Dawley rat pups (∼30/sex/group) from the F_2b generation were allowed to grow up to 10 to 12 weeks of age before mating. The rats in the treatment group were exposed directly to HCA-SX through feed, while prior to their weaning, they had indirect exposure to the test material during lactation. The dietary exposure levels were the same as those employed for the two-generation reproductive toxicity study, viz. 1000, 3000, or 10,000 ppm. Following mating at maturity, the pregnant rats were observed daily for clinical signs of adverse effects, and body weight and feed consumption were recorded. On day 20 of gestation, animals were subjected to a necropsy and cesarean section to examine the uterus, ovaries, and fetuses for assessment of different parameters of pregnancy and embryo-fetal defects. Despite a slight (13%) lowering of maternal body weight gain during gestation period in the group receiving 10,000 ppm HCA-SX, no evidence of maternal toxicity, adverse effects on the parameters evaluated for the gravid uteri, external abnormalities in the fetuses, soft tissue abnormalities in the fetuses, or skeletal abnormalities in the fetuses were noted. Based on the results of this developmental toxicity study, conducted in continuation of a two-generation reproductive toxicity study, HCA-SX was not found to be teratogenic in the Sprague-Dawley rat at the dietary exposure levels of 1000, 3000, and 10,000 ppm, equivalent to the dose levels of 103, 352, or 1240 mg/kg/day, respectively.

KEYWORDS :

• Hydroxycitric Acid
• Garcinia cambogia Extract
• Weaning
• Teratogenicity
• Gestation
• Embryo

ABBREVIATIONS
FDA	=	Food and Drug Administration;
DSHEA	=	Dietary Supplement Health and Education Act;
CHA	=	(-)-Hydroxycitric acid;
OECD	=	Organization for Economic Co-operation and Development;
NOAEL	=	no observed adverse effect level; ppm = parts per million.

ABBREVIATIONS
FDA	=	Food and Drug Administration;
DSHEA	=	Dietary Supplement Health and Education Act;
CHA	=	(-)-Hydroxycitric acid;
OECD	=	Organization for Economic Co-operation and Development;
NOAEL	=	no observed adverse effect level; ppm = parts per million.