FAO/WHO Consultation on Health Implications of Acrylamide in Food

1. FAO/WHO Consultation on Health Implications of Acrylamide in Food Dr. Manfred Lützow Food and Nutrition Division Food and Agriculture Organization of the United Nations

2. “Appetizer” • How all started ... • What did we know before? • New findings! • First assessments ... • and recommendations for ... • Future research

3. Acrylamide - a versatile molecule CH2=CHCONH2 Building block for water-soluble polymers used as additives for: • water treatment, • enhanced oil recovery, • flocculants, • papermaking aids, • thickeners, • soil conditioning agents, • sewage and waste treatment • ore processing, and permanent-press fabrics” CAS No. 79-06-1

4. Acrylamide - toxicology • Proven neurotoxic compound in animals and in humans • Effects range from drowsiness to incoordination, hallucinations, confusion, abnormal sensation, muscle weakness, incoordination • Genotoxic compound with the potential to affect the germinal cells thus leading to hereditary changes • Causing cancer in laboratory animals (rats) • Studies in humans (e.g. 8000 workers in China) which were positive on neurotoxicity failed to prove relationship with cancer in humans (too small numbers ?)

5. Handling instructions

6. Acrylamide: limits • WHO (1985): “The concentration in the workroom air should not exceed 0.1 mg/m3.” • WHO (1993) “a guideline value associated with an excess lifetime cancer risk of 10-5 is estimated to be 0.5 µg/litre” • OSHA (1990): “The permissible exposure limit (PEL) is 0.3 milligrams per cubic meter of air (mg/m3) as an 8-hour time-weighted average (TWA). “ • FDA/BGA/EU: various limits for food due to the migration from packaging materials

7. The Hallands’s tunnel In 1997, during the building of a tunnel in Sweden, concern was raised on the use of acrylamide and related compounds as building materials (as a component of grout): “For 23 subjects there was strong evidence indicating that peripheral nervous functions were impaired due to occupational exposure to NMA or acrylamide. Environmental effects due to contamination of the drinking water were also observed that led to the development of severe neurological symptoms among cows and the death of fish downstream.”

8. How do you know ... ... whether somebody had been exposed to acrylamide ? Acrylamide binds to haemoglobin! Biomarker: AA-Hb adduct Level of adduct may reflect exposure to acrylamide over last four months

9. New research I “Clear-cut dose-response associations were found between the Hb-adduct levels and PNS symptoms. Thirty-nine percent of those with Hb-adduct levels exceeding 1 nmol/g globin experienced tingling or numbness in their hands or feet. For 23 workers there was strong evidence of PNS impairment due to occupational exposure to acrylamide. All but two had recovered 18 months after the cessation of exposure.”

10. New research II “Forty-seven workers had Hb-adduct levels within the normal background range (0.02-0.07 nmol/g globin) ...” 2000 Question: what is the source of the acrylamide for this “background” ? Food ? Something else ? “For testing of the hypothesis that this adduct originates from acrylamide formed in cooking, rats were fed fried animal standard diet for 1 or 2 months. These animals exhibited a strong increase of the level of the studied Hb adduct, compared to control rats fed unfried diet.”

11. Sweden: April 2002 “A scientific group at the University of Stockholm ... has found that acrylamide is formed during heating of starch-rich foods to high temperatures. The Swedish National Food Administration has developed a new, rapid method for the analysis of acrylamide in foods. Analysis has shown that acrylamide is present in a large number of foods, including many regarded as staple foods. The levels of acrylamide differ widely within each food group analysed.”

12. First reactions

13. FAO/WHO Consultation ... ... on the Health Implications of Acrylamide in Food WHO, Geneva, 25-27 June 2002 This rapidly organised consultation reviewed the available information, drew some preliminary conclusions and recommended further research and actions. Report available at www.fao.org/es/esn/jecfa

14. Main findings The Consultation recognized the presence of acrylamide in food as a major concern in humans based on the ability to induce cancer and heritable mutations in laboratory animals. Based on available data, no threshold of toxicity! The Consultation provided a range of recommendations for further information and new studies to better understand the risk to human health posed by acrylamide in food. The Consultation also provided some advice to minimize whatever risk exists, including avoiding excessive cooking of food, choosing healthy eating, investigating possibilities for reducing levels of acrylamide in food, and establishing an international network on acrylamide in food.

15. Methods of analysis • Interlaboratory validation of analytical methods covering a range of different food types should be conducted. • Reference materials and standards for proficiency testing should be prepared and distributed. • Low-cost and simple method(s) for routine monitoring of acrylamide in food should be developed.

16. Modes of formation, fate and levels of acrylamide in food • The relation between acrylamide levels and processing/cooking conditions should be systematically examined. • Hypothesis-driven model studies are needed to elucidate sources, mechanism(s) of formation and fate of acrylamide in heated foodstuffs. • Optimization of formulation, processing and cooking conditions to minimize and possibly eliminate acrylamide levels in foods prepared industrially and at home should be investigated. • The range of foods investigated needs to be extended to include staple foods from different regions and diets.

17. Dietary exposure I • Further data on the levels of acrylamide in food, particularly staple foods consumed in developing countries, needs to be obtained in order to refine the estimates of dietary exposure. • In collecting data the emphasis should be on foodstuffs contributing most to exposure. In addition to food with the highest values, foods with lower values but high levels of consumption should be sampled. • A consistent system for collecting and describing the available data should be used. [e.g. GEMS/Food could provide a structure for data collection and reports and could provide an indication of important staple foods in each of the regions of the world.

18. Dietary exposure II • Developing and other countries with insufficient information for determining population-level dietary exposures to acrylamide should consider generating interim information relevant to their own circumstances. [...] • Given the state of knowledge on methods of formation and levels of acrylamide in food, biomarkers of exposure are likely to provide the most direct means of evaluating exposures to acrylamide from food and other sources. These biomarkers need to evaluated and calibrated, and their correlation with dietary intakes should be investigated. • Other sources of exposure to humans to acrylamide should be investigated to better define the relative contribution of food, smoking and other sources including the potential for endogenous formation of acrylamide.

19. Toxicity of acrylamide I • More data are required on the absorption, metabolism, distribution and excretion of acrylamide in humans by the oral route to permit more informed estimates of risk to humans • The bioavailability of acrylamide from food should be determined. • Cancer epidemiology and testicular toxicity in populations of known high exposure, such as occupationally exposed workers with neurotoxic signs and high levels of haemoglobin adducts, should be studied. • Quantitative risk assessment models should be investigated on the basis of scientific merit and uncertainty of estimates.

20. Toxicity of acrylamide II • The toxicity and carcinogenicity of glycidamide need to be studied. • The dose-response characteristics of acrylamide and glycidamide relative to toxicity, disposition, and binding to DNA and macromolecules need to be further assessed. • Genotoxic effects on somatic and germ cells using genome-wide expression profiling should be studied. • The relationship between adducts with haemoglobin and DNA in different organs should be explored. • Application of new methods in biological research may be helpful in clarifying whether it is possible to establish a threshold for the genotoxicity of acrylamide.

21. Interim advice • Food should not be cooked excessively, i.e. for too long or at too high a temperature. However, all food, particularly meat and meat products, should be cooked thoroughly to destroy foodborne pathogens. • The information available on acrylamide so far reinforces general advice on healthy eating. People should eat a balanced and varied diet, which includes plenty of fruit and vegetables, and should moderate their consumption of fried and fatty foods. • The possibilities for reducing the levels of acrylamide in food by changes in formulation, processing and other practices should be investigated. • An international network “Acrylamide in Food” should be established inviting all interested parties to share relevant data as well as ongoing investigations.