Studies of the Toxicological Potential of Capsinoids: VIII. A 13-Week Toxicity Study of Commercial-Grade Dihydrocapsiate in Rats

Abstract

Dihydrocapsiate, (4-hydroxy-3-methoxybenzyl 8-methylnona- noate; CAS No. 205687-03-2) is a naturally occurring capsinoid compound found in nonpungent chili peppers. Although the safety of synthetically produced dihydrocapsiate has been previously evaluated, the purpose of this 13-week gavage toxicity study is to evaluate dihydrocapsiate produced with a slightly modified manufacturing process. Sprague-Dawley rats, 10 rats/sex/group, 6 weeks of age at study initiation, were administered the dihydrocapsiate daily by gavage at dose levels of 0 (vehicle), 100, 300, or 1000 mg/kg/day. The rats were observed for antimortem and postmortem signs of toxicity, including changes in clinical signs, body weights, food consumption, water intake, ophthalmology, clinical pathology (clinical chemistry, hematology, urinalysis), tissue findings (macroscopic and microscopic examination), as well as organ weights. There were no changes observed in clinical signs, body weight, food consumption, water intake, ophthalmology, urinalysis, hematology, or blood chemistry that were attributable to the administration of dihydrocapsiate. The only change observed attributable to the dihydrocapsiate administration involved the liver and that change occurred only at the high dose (1000 mg/kg). Both sexes had an increase in organ weights, but this increase correlated with a change in histopathology (i.e., hepatocyte hypertrophy) only in the males. No dihydrocapsiate-related histopathological changes were observed in males at doses < or = 300 mg/kg or in females at any of the doses tested (< or = 1000 mg/kg). It was concluded that the no observed adverse effect level (NOAEL) of dihydrocapsiate was 300 mg/kg/day for male rats and 1000 mg/kg/day for female rats in this 13 week gavage study.

Studies of the Toxicological Potential of Capsinoids: V. Genotoxicity Studies of Dihydrocapsiate

“…Unassigned animals were euthanized by C02 inhalation. Individual body weights on the day of grouping were in the range of 171 to 250 g. Based on the results of the 13-week toxicity study of the test substance (Watanabe et al 2008c), the low-dose adverse effect level in males (1000 rug/kg/day) was selected as the high dose in this study and half of that dose (i.e., 500 mg/kg/day) was chosen as the low dose. The test substance was dissolved in the vehicle and administered to rats orally once daily for 28 consecutive days by gavage at a volume of 5 ml/kg BW.…”

“…The target organs were selected based on findings in previous studies. The 13-week repeated administration study revealed findings suggesting effects on the liver (Watanabe et al 2008c) and the kidney is the major excretion pathway . Oral administration would result in a relatively high concentration of the test material in the intestinal tract.…”

Capsiate Supplementation Reduces Oxidative Cost of Contraction in Exercising Mouse Skeletal Muscle In Vivo

“…Capsiate is a nonpungent capsaicin-related compound extracted from the fruit of the CH-19 sweet pepper wherein it is highly concentrated [ 2 ]. Chronic administration of capsiate has been reported to promote fat loss in both humans [ 3 ] and rodents [ 4 , 5 ] in the absence of any adverse effect or toxicological changes [ 6 , 7 ]. This anti-obesity effect would be mediated by an acceleration of basal fatty-acid oxidation in mitochondria [ 3 , 5 , 8 ].…”

A 90-day toxicity and genotoxicity study with high-purity phenylcapsaicin

“…63 The observed diffuse hepatocellular hypertrophy described corresponds to previously reported findings of hepatocellular hypertrophy/increased liver weights in capsaicin analogue studies. 57,62,64,65 It has been suggested that low incidences are within the normal range for rats 62 and that hepatocellular hypertrophy when observed alone can be an adaptive response. 66 Again, hepatocellular hypertrophy alone is not considered to be of adverse nature.…”