Risk assessment of ochratoxin A in food

Abstract

The European Commission asked EFSA to update their 2006 opinion on ochratoxin A (OTA) in food. OTA is produced by fungi of the genus Aspergillus and Penicillium and found as a contaminant in various foods. OTA causes kidney toxicity in different animal species and kidney tumours in rodents. OTA is genotoxic both in vitro and in vivo; however, the mechanisms of genotoxicity are unclear. Direct and indirect genotoxic and non-genotoxic modes of action might each contribute to tumour formation. Since recent studies have raised uncertainty regarding the mode of action for kidney carcinogenicity, it is inappropriate to establish a health-based guidance value (HBGV) and a margin of exposure (MOE) approach was applied. For the characterisation of non-neoplastic effects, a BMDL ₁₀ of 4.73 μg/kg body weight (bw) per day was calculated from kidney lesions observed in pigs. For characterisation of neoplastic effects, a BMDL ₁₀ of 14.5 μg/kg bw per day was calculated from kidney tumours seen in rats. The estimation of chronic dietary exposure resulted in mean and 95th percentile levels ranging from 0.6 to 17.8 and from 2.4 to 51.7 ng/kg bw per day, respectively. Median OTA exposures in breastfed infants ranged from 1.7 to 2.6 ng/kg bw per day, 95th percentile exposures from 5.6 to 8.5 ng/kg bw per day in average/high breast milk consuming infants, respectively. Comparison of exposures with the BMDL ₁₀ based on the non-neoplastic endpoint resulted in MOEs of more than 200 in most consumer groups, indicating a low health concern with the exception of MOEs for high consumers in the younger age groups, indicating a possible health concern. When compared with the BMDL ₁₀ based on the neoplastic endpoint, MOEs were lower than 10,000 for almost all exposure scenarios, including breastfed infants. This would indicate a possible health concern if genotoxicity is direct. Uncertainty in this assessment is high and risk may be overestimated.

Keywords: Ochratoxin; dietary exposure assessment; hazard characterisation; margin of exposure approach; risk characterisation.

Figure 1

Chemical structure of ochratoxin A, B and C

Figure 2

Modified forms of OTA arising from food processing

Figure 3

Modified forms of OTA arising from plant metabolism

Figure 4

Metabolic pathways of OTA in animals and humans

Figure 5

Hypothetical reactive metabolites of OTA and their products

Figure 6

Conjugates of OTA metabolites with GSH and their corresponding mercapturic acids

Figure 7

Number of food samples in the final data set encoded by European countries: n = 73,891 food samples with results for OTA

Figure 8

Number of food samples in the final data set reported by year for the n = 73,891 food samples with results for OTA

Figure 9

Contributors of exposure of OTA among different countries/surveys in ‘Toddlers’ and ‘Other Children’

Figure 10

Contributors of exposure of OTA among different countries/surveys in ‘Adolescents’ and ‘Adults’

Figure 11

Contributors of exposure of OTA among different countries/surveys in ‘Elderly’ and ‘Very Elderly’