Module 3 - Strategic case studies in practice

nitroso-thiazolidine-4-carboxylic acid (NTCA) and N- nitroso-2-hydroxymethyl-thiazolidine-4-carboxylic acid (NMTCA). These non-volatile N- nitrosamines are however considered of low concern based on the data available and/or structure-activity-relationship (SAR) considerations (EFSA, 2017). The Lee-study estimates for NDMA and NDEA in various meat/poultry products (spanning different processing and cooking methods) is 0.3 to 5.7 µ g/kg and 0.2-1.0 µ g/kg, respectively. Both the Gushgari & Halden study and the Lee-study indicate that TNA levels in most food groups are <10 µ g/kg (many in the range of 5-10 µ g/kg) and that the overall TNA levels have decreased since the 1970s and 1980s. A smaller review by Herrmann et al. (2015), who reviewed publications of the period 1990–2010 in three European countries (Finland, the Netherlands and Germany), reported mean estimates of exposure to volatile N- nitrosamines from all foods ranging from 1.0 ng/kg bw/day (NDMA only) to 12 ng/kg bw/day (sum of NDMA, NPYR, NPIP). Furthermore, it was estimated that the classical volatile N- nitrosamines (NDMA, NPYR, NPIP, NDEA) accounted for approximately 90% of the total exposure to volatile N- nitrosamines with NDMA and NPYR contributing to 40–50%. In Switzerland, the exposure to N- nitroso compounds (NOCs) via food (excluding drinking water) is estimated to be around 1,000 ng/day (20 ng/kg bw/day) with NDMA contributing up to 200 ng [Tricker et al. (1991), Lutz (1999)]. According to an evaluation of the European Food Safety Authority (EFSA), the combined daily intake of NDMA and NDEA via processed meat ranges from 0.5 to 1.7 ng/kg on average in adults in Europe (EFSA, 2017). Based on the evaluated studies, the EFSA panel noted that NDMA was the main compound contributing to mean overall human N- nitrosamine exposure. NDMA accounts to approximately 90% and NDEA to approximately 10% of human exposure to volatile N- nitrosamines. An assessment assumed an, on average, 100 – 1,000 ng/day corresponding to 2 – 20 ng/kg bw/day exposure to NDMA from contaminated beverages and food, air and water pollution (Keszei et al. 2013, WHO). Other volatile N- nitrosamines found were NPIP, NDBA, NPYR. Unpublished data on actual levels of nitrosamines in cooked/processed food analysed NDMA, NDEA, NDIPA, NDPA but only found NDMA (and N-nitrosopiperidine, NPip) 0.7-0.9 ppb or 14-17 ng/day consumption according to the Ad-hoc Experts Group. Human urine samples : Assessment of nitrosamine levels in urine samples also provides an indication of overall (exogenous and endogenous) nitrosamine exposure. Based on published literature (1994 to 2016), the mean NDMA range in urine samples (from European and non-European countries) ranges between <10 ng/L and 1,920 ng/L (Krauss et al. 2009). For studies from European countries (Switzerland, Netherlands), the NDMA range was 83-1,134 ng/L based on average urinary volume of 1.5L per day which, assuming that there is not a 100% correlation between exposure/uptake and elimination, would indicate that the total NDMA exposure is very likely larger than ~1 µ g/day for at least a part of the population. Considering that NDMA is often found as a proportion of the TNA measurements (e.g. average 2.2 µ g/kg NDMA across food groups where the TNA levels are ~5-9 µ g/kg across food groups in the Gushgari & Halden study), this would indicate that the TNA levels are also greater in urine samples. However, the reliability of the measures is unclear as is the relationship between external exposure and endogenous generation of NDMA specifically and volatile nitrosamines in general. Estimations are based on simulation model estimates, but the endogenous part also may be substantial.

2.4.1.2. Exposure to endogenous N-nitrosamines

Exposure to endogenously produced N- nitroso compounds (ENOCs) raises an equal concern as exposure to exogenous NOCs. Formation of ENOCs in the upper gastrointestinal tract from nitrosatable amines depends on the simultaneous presence of nitrite. Sufficient nitrite ingestion and formation of nitrite from ingested nitrate is a key factor for nitrosation. There is, however, no experimental proof for

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