Looking forward: How can mercury contamination harm the next - PowerPoint PPT Presentation

Looking forward: How can mercury contamination harm the next generation - the need for precaution Philippe Grandjean University of Southern Denmark Harvard School of Public Health

Presenter: Philippe Grandjean, MD, DMSc Professor and Chair, Environmental Medicine, University of Southern Denmark Adjunct Professor, Harvard School of Public Health Conflict of interest declaration: Research support only from public sources (NIH, EC, Danish research councils) Adviser to Danish National Board of Health Member of the Danish delegation at own expense No support from NGO organizers

Widespread Diffuse Focal

Sensitive brain development • Cell division* • Differentiation • Migration** • Axon formation*** • Generation of synapses**** • Weeding of synapses *In third trimester about 12,000 nerve cells are formed every minute **Distances up to 1,000 times the size of the cell ***Total length by age 20 years: 176,000 / 149,000 km (m/f) ****Up to 1,000 new synapses per second early postnatally

Developmental Origin of Health And Disease (DOHAD) Early-life exposures to neurotoxic chemicals Development/ programming Functional maturation Neurological disease and degenerative changes

Long-term follow-up of large birth cohorts

Framework For Understanding NEUROCOGNITIVE TOXICANTS TRAITS attention span NEUROPHYSIOLOGY y t i NEURO- v memory i s aggression l u p m DEVELOPMENT i s GENETICS o a c d i j a u l s testing t m e n g t n i d NEUROANATOMY a e r s l l i k s SOCIAL ENVIRONMENT executive function introversion/ clinical extroversion diagnosis DEVELOPMENTAL learning SYNDROMES disability ??? ADHD Asperger syndrome autism ECONOMIC IMPACT Revised from In Harm’s Way

Objective measure: Speed of electrical signals in the brain Delayed electrical signals at higher mercury exposures (brainstem auditory evoked potentials at age 14 years) WHO exposure limit U.S.EPA exposure limit Murata et al., Journal of Pediatrics, 2004

Modern imagining methods show that children with high prenatal pollutant exposure must activate brain regions not needed by controls Finger tapping with the left hand activates motor cortex on right AND left Increased prenatal exposure to MeHg (N = 3) In non-exposed controls, only the right motor cortex is activated Controls (N = 3) (R.F.White et al., 2011)

Genetic susceptibility: Change in IQ at age 8 for 10-fold increase in prenatal MeHg exposure and number of mutations in PGR, PON1, TF, and BDNF WISC-III outcomes Log 10 (Cord Hg Slices (ng/g)) Julvez J et al. Epidemiology, September 2013 Total IQ Estimate ( β ) 95 % CI P-int. SNP Score (0-1) (n=193) 15.5 4.3 to 26.6 SNP Score (2-3) (n=486) 2.6 -4.8 to 10.2 0.23 SNP Score (4-7) (n=177) -8.7 -20.2 to 2.9 0.003 Verbal IQ 13.9 2.6 to 25.2 SNP Score (0-1) 3.3 -4.6 to 11.3 0.28 SNP Score (2-3) -3.3 -15.7 to 9.1 0.052 SNP Score (4-7) Performance IQ 13.1 0.2 to 26.0 SNP Score (0-1) 1.2 -7.0 to 9.4 0.36 SNP Score (2-3) -12.9 -25.9 to 0.0 0.002 SNP Score (4-7)

Time course of recognition of MeHg developmental neurotoxicity Hair-Hg Silent pandemic Neurotoxicant dose (inverted scale) Number of subjects affected < 0.5 Genetic predisposition <1 Subclinical effects 3-5 in child populations 5-10 Neurotoxicity >10 In adults Poisoning incidents >50 Time of recognition Revised from Grandjean & Landrigan, Lancet, 2006

Calculating the IQ value (Bellanger et al., 2013) • Life-time earnings based on US data • Future earnings converted to present-day value by discounting (3% per year) • National values for life-time earnings adjusted for purchasing power parity • Additional adjustment for productivity • EU value ~€13,600 (2008) for 1 IQ point • Other benefits (intangible/direct) ignored

Annual costs in Europe for IQ losses (€ billion) due to mercury • Denmark: ~0.1 • Faroe Islands ~0.003 • France: ~1.2 • Italy: ~1.4 • Spain: ~4.5 • United Kingdom: ~0.4 • Total EU: ~9.3 *From Bellanger et al., 2013)

Complementing the Minamata Convention • In the short term, the convention will not prevent excess exposures that are dangerous to developing brains • Dietary fish/seafood advisories are needed and must be targeted to local conditions • Hair-mercury analyses are needed to assess national and regional exposure levels – and to identify individuals at risk • Analytical capacity for hair-mercury exists to provide assistance at a global level