Human Biomonitoring Requires Validation

Food safety is at the heart of all: consumers, policy makers, food producers, scientists, and so on. EU Regulation 178/2002 (1) lays down the ‘general principles and requirements of food law, establishing the European Food Safety Authority (EFSA) and the procedures in matters of food safety’. Hence EFSA, based in Parma, Italy, is an integral part of the EU’s food safety system. EFSA’s mission is to contribute to the safety of the EU food chain by providing scientific advice to risk managers, by communicating risks to the public, and by cooperating with Member States and other parties to deliver a coherent, trusted food safety system in the EU (2). EFSA’s core responsibilities are the delivery and communication of advice on general scientific assessment priorities, and the evaluation of food and feed products that require a safety assessment before they can be used in the EU market.

EFSA conducts risk assessments using the four steps of the risk assessment paradigm: hazard identification, hazard characterization, exposure assessment and risk characterization. When considering exposure assessment, dietary exposure is most frequently estimated by combining information on the levels in food of a given substances – such as a contaminant, pesticide, a food additive, or micronutrient – with food consumption data from national dietary surveys. A more precise quantification of exposure that is closer to the ultimate health effect can be achieved by using information from human biomonitoring. In particular, biomarkers can be used to estimate internal levels of exposure, which is particularly relevant when we need to assess combined exposure from different routes and sources.

Notably, human biomonitoring can be done on all compounds that are present in foods, either naturally occurring or added, or present as contaminants.

Human biomonitoring is a promising tool to inform risk assessment for human health; for example see recent reflections in the USA (3). EFSA is closely following developments in human biomonitoring, such as the HBM4EU project – a joint effort involving 26 countries, the European Environment Agency and the EC (4) and the EU Joint Programming Initiative on biomarkers (5).

To date, human biomonitoring data have been used only to a small extent in EFSA. Human biomonitoring for food safety purposes has already been used to inform EFSA risk assessments; for example, bisphenol A (6), cadmium (7), lead (8), methylmercury (9) and the mycotoxin deoxynivalenol (10). For pesticides, EFSA recently commissioned a ‘Review of human biomonitoring and its application to exposure assessment for food safety’ (11) and a project on ‘Human biomonitoring data collection from occupational exposure to pesticides’ (12). In addition, a recently published scientific opinion on epidemiology expressly indicated human biomonitoring as a tool to improve the characterization of exposure and therefore contribute to a better use of epidemiological studies in risk assessment of pesticides (13).

We believe that measuring a biomarker in human blood, urine or hair requires a prudent and well thought-out approach. Any biomarker requires validation, as well as standardization and harmonization (14). Analytical validation should follow recommendations such as those under the 17025/2017 (15) or equivalent system, which contribute to the reliability of the results being produced. Physiological validation should follow the scientific justification of the biomarker measured and its response to changes in exposure or effect, such as those used for the scrutiny of scientific substantiation of health claims (16)(17).

Next steps for greater application of human biomonitoring into risk assessment for EFSA:

• Human biomonitoring data can be used to “validate“ dietary exposure estimates and also to detect health effects; 
• Human biomonitoring data are particularly important in exposure assessment and could play an important role in post-market monitoring;
• Human biomonitoring data need to be combined with other data and tools for interpretation in risk assessment, such as information on dietary intake (e.g. from food frequency questionnaires, 24h dietary recall methods); 
• Access to individual human biomonitoring data is needed, which requires a data format compatible with EFSA’s format for chemical concentration and intake data.

Just measuring substances in blood or urine is a clear waste of energy and resources – and scientifically wrong. The challenge is to measure the right biomarker, in the right place, at the right moment, with validated analytical methods. This brings the scientific areas of analytical chemistry in close proximity to physiology, nutrition and toxicology.