Chemical contaminants: pesticides, additives, endocrine-disrupting compounds

1. Chemical contaminants:pesticides, additives, endocrine-disrupting compounds The Queen’s Medical Research Institute Medical School Main Hospital Richard M Sharpe E-mail: r.sharpe@ed.ac.uk

2. Perspectives of my talkAdditives versus Contaminants • What we deliberately add to our (processed) food/drink results in high exposure, in some cases endocrine disruption and resulting health disorders • Food contaminants result in low level exposures, some of which have endocrine disrupting potential. This exposure may be associated with health disorders, especially obesity • Diet, in particular a high fat Western style diet, is the main determinant of exposure to contaminants (?and food additives)

3. High amounts of refined sugar in our diets causes ‘endocrine disruption’ leading to obesity

4. Mouse exposure to common emulsifiers inducescolitis and obesity/metabolic dysfunction CMC= carboxymethylcellulose P80= polysorbate-80 From: Chassaing et al (2015) Nature 519: 92-96

5. Pesticide residue levels in the EU From: EU Policy for a sustainable use of pesticides, 2007

6. Prenatal exposure to POPs and childhoodrisk of obesity and increased blood pressure The problem with all such studies is that the intake of POPs (which are highly fat-soluble) is very much determined by the diet of the mothers (and perhaps their mothers)

7. Association between phthalate exposureand obesity/diabetes/metabolic syndrome

8. Higher DEHP exposure in humans is associated with lower vitamin D levels Obesity is consistently associated with low vitamin D levels – what determines obesity is calorific over-consumption (including fats) From: Johns et al (2016) J Clin Endocrinol Metab 101: epub online

9. An alternative hypothesisto explain the phthalate (or other EDC) association studies Higher phthalate (eg DEHP) exposure in the mothers High fat diet (ie Western diet) DEHP and disorder are associated Obesity or other disorder

10. DEHP ingestion is associated with highfat foods High meat & dairy food consumption From: Serrano et al (2014) Environ Health 13: 43

11. One dietary determinant of DEHPexposure is fast food consumption From Zota et al (2016) Environ Health Perspect 124: 1521-1528

12. Sources of human exposure to diethyl hexylphthalate (DEHP) and dibutyl phthalate (DBP)

13. Sources of human exposure to diethyl hexylphthalate (DEHP)

14. Diet and ‘obesogenic’ chemical (EDC) exposures • ~70% of intake of DEHP (?DINP) is via our diets • >95% of intake of Bisphenol-A (BPA) is via our diets • Our intake of POPs is also determined largely by diet • Does a modern Western diet mean that we are more highly exposed to each of these? Is this acceptable? Irrespective of whether these exposures are causally linked to obesity/other disorders, they add nothing to the foods in which they are present. So why are they there?

15. The mixtures issue • Safety and regulation of chemicals is on an individual basis • We are exposed to 100s of environmental chemicals, most at low levels, and for most at safe levels (ie below TDI – tolerable daily intake) • We are exposed to 10s (probably 100s) of EDCs, so do these have combined effects even though we are exposed to ‘safe’ levels of each individually?

16. Effects of perinatal exposure to mixturesof ‘anti-androgenic’ chemicals in rats Data courtesy of Earl Gray (EPA, USA)

17. Similar mixtures study with 10 EDCs From: Rider et al (2010) Int J Androl 33:443-462

18. Implications of the mixtures issue • Does this mean that we must assume that ‘real world’ mixtures pose a risk to human health, with profound implications for chemicals regulation? • Or are we still best to take an evidence-based approach – the challenge being to obtain the most informative type of evidence (ie from mixtures studies in humans)? • If we decide on a precautionary approach, how will we handle things like sugar and (EDC-active) medicines that are released to our environment?

19. Pregnancy exposure to EDC mixtures (n=27)and child obesity at age 7

20. The End!