Risk assessment of N‐nitrosamines in food

Abstract

EFSA was asked for a scientific opinion on the risks to public health related to the presence of Nnitrosamines (N-NAs) in food. The risk assessment was confined to those 10 carcinogenic N-NAs occurring in food (TCNAs), i.e. NDMA, NMEA, NDEA, NDPA, NDBA, NMA, NSAR, NMOR, NPIP and NPYR. N-NAs are genotoxic and induce liver tumours in rodents. The in vivo data available to derive potency factors are limited, and therefore, equal potency of TCNAs was assumed. The lower confidence limit of the benchmark dose at 10% (BMDL 10 ) was 10 μg/kg body weight (bw) per day, derived from the incidence of rat liver tumours (benign and malignant) induced by NDEA and used in a margin of exposure (MOE) approach. Analytical results on the occurrence of N-NAs were extracted from the EFSA occurrence database (n = 2,817) and the literature (n = 4,003). Occurrence data were available for five food categories across TCNAs. Dietary exposure was assessed for two scenarios, excluding (scenario 1) and including (scenario 2) cooked unprocessed meat and fish. TCNAs exposure ranged from 0 to 208.9 ng/kg bw per day across surveys, age groups and scenarios. 'Meat and meat products' is the main food category contributing to TCNA exposure. MOEs ranged from 3,337 to 48 at the P95 exposure excluding some infant surveys with P95 exposure equal to zero. Two major uncertainties were (i) the high number of left censored data and (ii) the lack of data on important food categories. The CONTAM Panel concluded that the MOE for TCNAs at the P95 exposure is highly likely (98-100% certain) to be less than 10,000 for all age groups, which raises a health concern.

Regulatory Highlights

“…The EFSA CONTAM Panel ultimately concluded that the MOEs calculated from the TCNA BMDL10s are below 10,000 in both scenarios, which raises a health concern. Attributing a lower potency factor to NMA, NDPA, NDBA, NSAR, NPIP, and NPYR would not change the above conclusion …”

“…Consequently, expert committees of the United Nations Food and Agriculture Organization (FAO) and the World Health Organization (WHO), as well as other UN bodies (e.g., the United Nations Environment Programme), have used the MOE approach . The Joint FAO/WHO Expert Committee on Food Additives (JECFA) routinely uses the MOE approach for assessing the risk of genotoxic and carcinogenic contaminants in foods. ,, …”

N‐Nitrosamines: a potential hazard in processed meat products

“…The report lists the median toxic doses (TD 50 ) for ten nitrosamine species as follows: NDMA (0.0959), NMEA (0.05), NDEA (0.0265), NDPA (0.186), NDBA (0.691), N-nitrosomethyl-n-alkylamine (NMA) (0.142), NMOR (0.109), NPIP (1.11), NPYR (0.799), and N-nitrososarcosine (NSAR) (0.982) (mg kg −1 body weight per day). 64 Acceptable amounts for nitrosamines are calculated based on TD 50 values. 65 In a study where acceptable intakes (AI) were determined for 11 N-nitrosamine species, acceptable intake levels of NDMA, NDEA, NDBA, NMOR, NMPA, NPIP, N-nitrosodiisopropylamine (DIPNA) and N-nitrosoethylisopropylamine (EIPNA) species were calculated based on TD 50 and 0.145, 62, 8.2, 0.129, 0.106, 1.33, 4.5-29 mg kg −1 and 4.1 mg kg −1 d −1 , respectively.…”

C-Nitrosation, C-Nitration, and Coupling of Flavonoids with N-Acetyltryptophan Limit This Amine N-Nitrosation in a Simulated Cured and Cooked Meat

“…However, nitrite addition is nowadays largely questioned by public health agencies, as it appears to be involved in the formation of various N -nitroso compounds (NOCs). Processed meat products preserved with nitrite and/or nitrate are associated with the occurrence of N -nitrosamines, some of which being genotoxic and classified as probable human carcinogenics . A large investigation of the Danish and Belgian markets indicated that the mean contents in nonvolatile N -nitrosamines (129 and 285 μg/kg) were 100-fold higher than those in volatile N -nitrosamines (1.6 and 2.9 μg/kg) in various processed products including bacon, ham, and salami .…”