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 N-nitrosamines (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% (BMDL₁₀) 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.

Keywords: N‐nitrosamines (N‐NAs); cancer; exposure; food; genotoxicity; margin of exposure (MOE); occurrence.

Figure 1

NDMA metabolic pathways (modified from ATDSR, 2000)

Figure 2

Structures of 7‐Me‐Gua and O ⁶ ‐Me‐Gua

Figure 3

Metabolism of NDEA catalysed by CYPs

Figure 4

Structures of N7‐Et‐Gua, O ⁶ ‐Et‐Gua and O ⁴ ‐Et‐Thy

Figure 5

NMEA metabolic activation

Figure 6

Metabolism of NDPA (modified ATDSR, 2019)

Figure 7

Structures of propyl/hydroxypropyl DNA adducts

Figure 8

Formation and decomposition of 1‐nitrosomethylaminooxirane from NMVA, and formation of DNA adducts

Figure 9

Metabolism of NDBA and formation of O ⁶ ‐butylGua in DNA

Figure 10

Metabolism of NMOR

Figure 11

NPYR metabolism by α‐hydroxylation

Figure 12

DNA adduct formation from NPYR

Figure 13

NPIP metabolism by α‐hydroxylation

Figure 14

Formation of N ² ‐THP‐dGua

Figure 15

Structures of NTHZ and its metabolite

Figure 16

Metabolic pathways for NPhA (ATSDR, 2017)

Graph 1

Mean LB dietary exposure to the individual TCNAs for infants, toddlers and adult surveys (ng/kg bw per day) for scenario 1 and 2

Graph 2

Percentage contribution to the mean LB dietary exposure of the individual TCNAs for infants, toddlers and adult surveys for scenarios 1 and 2

Graph 3

Contribution of each food category at the level 1 of the Foodex2 classification to the mean LB dietary exposure to TCNAs, across for infants, toddlers and adult surveys for scenarios 1 and 2 (ng/kg bw per day)