Final Report on the Safety Assessment of Capsicum Annuum Extract, Capsicum Annuum Fruit Extract, Capsicum Annuum Resin, Capsicum Annuum Fruit Powder, Capsicum Frutescens Fruit, Capsicum Frutescens Fruit Extract, Capsicum Frutescens Resin, and Capsaicin1

Abstract

Capsicum-derived ingredients function as skin-conditioning agents--miscellaneous, external analgesics, flavoring agents, or fragrance components in cosmetics. These ingredients are used in 19 cosmetic products at concentrations as high as 5%. Cosmetic-grade material may be extracted using hexane, ethanol, or vegetable oil and contain the full range of phytocompounds that are found in the Capsicum annuum or Capsicum frutescens plant (aka red chiles), including Capsaicin. Aflatoxin and N-nitroso compounds (N-nitrosodimethylamine and N-nitrosopyrrolidine) have been detected as contaminants. The ultraviolet (UV) absorption spectrum for Capsicum Annuum Fruit Extract indicates a small peak at approximately 275 nm, and a gradual increase in absorbance, beginning at approximately 400 nm. Capsicum and paprika are generally recognized as safe by the U.S. Food and Drug Administration for use in food. Hexane, chloroform, and ethyl acetate extracts of Capsicum Frutescens Fruit at 200 mg/kg resulted in death of all mice. In a short-term inhalation toxicity study using rats, no difference was found between vehicle control and a 7% Capsicum Oleoresin solution. In a 4-week feeding study, red chilli (Capsicum annuum) in the diet at concentrations up to 10% was relatively nontoxic in groups of male mice. In an 8-week feeding study using rats, intestinal exfoliation, cytoplasmic fatty vacuolation and centrilobular necrosis of hepatocytes, and aggregation of lymphocytes in the portal areas were seen at 10% Capsicum Frutescens Fruit, but not 2%. Rats fed 0.5 g/kg day-1 crude Capsicum Fruit Extract for 60 days exhibited no significant gross pathology at necropsy, but slight hyperemia of the liver and reddening of the gastric mucosa were observed. Weanling rats fed basal diets supplemented with whole red pepper at concentrations up to 5.0% for up to 8 weeks had no pathology of the large intestines, livers, and kidneys, but destruction of the taste buds and keratinization and erosion of the gastrointestinal (GI) tract were noted in groups fed 0.5% to 5.0% red pepper. The results of 9-and 12-month extension of this study showed normal large intestines and kidneys. In rabbits fed Capsicum Annuum Powder at 5 mg/kg day-1 in the diet daily for 12 months damage to the liver and spleen was noted. A rabbit skin irritation test of Capsicum Annuum Fruit Extract at concentrations ranging from 0.1% to 1.0% produced no irritation, but Capsicum Frutescens Fruit Extract induced concentration-dependent (at 25 to 500 microg/ml) cytotoxicity in a human buccal mucosa fibroblast cell line. An ethanol extract of red chili was mutagenic in Salmonella typhimurium TA98, but not in TA100, or in Escherichia coli. Other genotoxicity assays gave a similar pattern of mixed results. Adenocarcinoma of the abdomen was observed in 7/20 mice fed 100 mg red chilies per day for 12 months; no tumors were seen in control animals. Neoplastic changes in the liver and intestinal tumors were observed in rats fed red chili powder at 80 mg/kg day-1 for 30 days, intestinal and colo...

Capsaicin reduces genotoxicity, colonic cell proliferation and preneoplastic lesions induced by 1,2-dimethylhydrazine in rats

“…On the other hand, Lee and Park have reported an association between capsaicin at high doses with mutagenicity and carcinogenicity (Lee and Park 2003). Furthermore, several preclinical studies have suggested that the chili extract or capsaicin alone can have co-carcinogenic effects on the stomach, liver, colon and skin in different chemically-induced carcinogenesis models (Agrawal et al 1986;Díaz Barriga Arceo et al 1995;Johnson 2007;Liu et al 2015). Considering that the molecular mechanisms underlying the putative effects of capsaicin on colon carcinogenesis are largely unknown, this study aimed at assessing the effects of capsaicin oral administration on DNA damage, cell proliferation, and apoptosis, as well as on the expression of the genes involved in oxidative metabolism, antioxidant activity, cell cycle, DNA repair and cell death pathways during the early stages of colon carcinogenesis induced by 1,2-dimethylhydrazine (DMH) in rats.…”

Affinin and hexahydroaffinin: Chemistry and toxicological profile

“…Several studies related capsaicin to weight loss in chronic feeding studies (Johnson, 2007;Lee, 1963). However, the 28-day study did not find that capsaicin nor other alkamides affect the daily consumption of standard food as reported (Choi et al, 2013).…”

Capsaicin reactivates hMOF in gastric cancer cells and induces cell growth inhibition

“…The actual percentage of capsaicin varies depending on the pepper source and method of extraction. 31 Therefore, in this study, we adopted semi-preparative HPLC method to get highly purified CAP product (purity >99%, Fig. 1B) to avoid potentially toxic impurities.…”