Epidemiology of Flame Retardants (mostly PBDEs)

Transcription

1 Epidemiology of Flame Retardants (mostly PBDEs) Tom Webster, DSc Department of Environmental Health Boston University School of Public Health Green Science Policy Institute Fire Retardant Dilemma: Beijing, 22 August

2 Outline: brief discussion of past epidemiology studies (primarily PBDEs) review some basic epidemiology principles with application to studies of flame retardants some thoughts about potential studies in China

3 Little health-related PBDE research on humans (yet): adult thyroid (Hagmar et al 2001) birth weight, thyroid (Mazdai et al 2003) testicular cancer (Hardell et al 2005) decreased birthweight (Chao et al 2007) cryptorchidism (Main et al 2007) sperm, adult males (Akutsu et al 2008) infant thyroid (Herbstmann et al 2008) thyroid, adult males (Turyk et al 2008) hormones, adult males (Meeker et al 2009) No time today to analyze/critique, only to give a flavor for what has been done. 3

4 Birth cohort: birth weight, thyroid (Mazdai et al 2003) USA, 2001, n=12 mother-infant pairs cord, maternal serum, 39 & 37 ng/g lw decreased birth weight & length (Chao et al 2007) Taiwan, , very small (n=20) breast milk, median 4 ng/g lw, penta cryptorchidism, hormones (Main et al 2007) Denmark/Finland, nested case control (very efficient design) breast milk (& placenta), median 4 ng/g lw penta infant thyroid, US (Herbstmann et al 2008) USA, , n=297 cord blood, 19 ng/g lw penta (BDE 47,100,153) weak effect, delivery mode 4

5 Adult cross-sectional: adult thyroid (Hagmar et al 2001) Sweden, Latvia, n=110 male serum,bde 47 only, median 1 ng/g lw sperm, adult males (Akutsu et al 2008) Japan, 2003, n=10 (pilot) serum median 3 ng/g lw thyroid, adult males (Turyk et al 2008) USA, , n=308 male serum, median 38 ng/g lw (~NHANES) hormones, adult males (Meeker et al 2009) USA, ?, n=24 (pilot), fertility clinic dust (serum not yet reported) 5

6 Some other PBDE studies under way: adult, longitudinal, hormones, USA (T. Webster) birth, thyroid, Canada (G. Webster) birth, thyroid, USA (Stapleton) maternal & birth, thyroid etc., USA (Eskenazi)* birth, hormones, male reproductive, neurological, Netherlands (Meijer) birth, neurobehavioral, USA (Herbstmann) child, autism, USA (Hertz-Piccioto) 6

7 Epidemiology of TDCPP (chlorinated tris) Retrospective occupational cohort (TDCPP production) vs. US population Lung cancer elevated, but Unpublished (Stauffer Chemicals, cited in NRC 2000, IPCD 1998) 7

8 Goal of environmental/occupational epidemiology In a real population, measure: Effect = f (Exposure) Validity (unbiased, i.e., correct) Precision (narrow confidence intervals, power) Acknowledge strengths & limitations of results (ideally direction & possible magnitude of any biases) Discuss generalizability from studied population to others. We do not need a random sample to obtain a valid study 8

9 Validity (unbiased, i.e., correct) Because we are studying toxic chemicals, we cannot randomize people to exposure or not as in clinical trials. observational study Look for natural experiments Validity is major concern e.g., confounding, exposure measurement error 9

10 The usual picture exposure health effect Health effect = f (Exposure) 10

11 Exposure Disease Continuum sources environment exposure internal dose early effect health effect Health effect = f (Exposure) 11

12 sources environment exposure internal dose early effect health effect physical chemistry environmental processes behavior of people 12

13 sources environment exposure internal dose early effect health effect pharmacokinetics absorption distribution metabolism elimination 13

14 Other risk factor sources environment exposure internal dose early effect health effect toxicology/biology time other risk factors * Confounding: occurs if other risk factors for the outcome are also associated with exposure 14

15 exposure assessment is often one of the most difficult aspects of environmental/ occupational epidemiology sources environment exposure internal dose early effect health effect Effect = f (Exposure) 15

16 Use of biomarker as exposure measure, e.g., serum PBDEs sources environment exposure internal dose early effect health outcome Health outcome = f (biomarker of exposure) Often a superior measure of exposure, but some caution needed 16

17 Caution 1 Biomarkers often log-normal (e.g., PBDEs) Need exposure contrast, e.g., high vs. low Need efficient way to find highly exposed. Better understanding of exposure helps. 17

18 Caution 2 Possibility of reverse-causation in cross-sectional studies--where we measure exposure & disease at the same time (i.e., disease causes elevated biomarker) e.g., need to consider for PBDE serum levels vs. hormone levels, metabolic outcomes longitudinal studies (follow over time) 18

19 Caution 3 The optimal biomarker depends on the chemical as well as the outcome PBDEs have varying halflives in humans: BDE 209: weeks BDE 183: months BDE 47, 153: on the order of years? current blood level reflects past exposure important for study design outcomes may depend on exposure at particular points in time (e.g., developmental exposure, cancer latency) 19

20 Caution 4 Error in measuring exposure is often inevitable e.g., measuring at wrong time e.g., measure wrong thing: e.g., does outcome depend on average or peak or In several common cases, exposure measurement error will tend to hide associations ( bias toward the null ) 20

21 Outcome measures sources environment exposure total absorbed dose early effect health outcome Markers of early effect may often be more sensitive than outright disease (e.g., subclinical hormone changes vs. infertility, subclinical neurobehavioral ) 21

22 Given what we know about PBDE toxicology: Adult: hormone changes --> cross-sectional studies --> longitudinal studies Developmental: reproductive system neurobehavioral outcomes --> birth cohorts measure mother s serum level (and/or cord blood or breast milk) Potentially others 22

23 China--PBDE exposure studies General population studies: A few, mostly breast milk, mostly small suggest median serum levels about 2-5 ng/g lw about European & <USA some difference in congener profiles though --Bi 2006, Sudaryanto 2008, Haraguchi 2009, Zhu 2009 While studies of this level of exposure have been done, North America may provide better location 23

24 Occupational studies, or nearby residents electronics dismantling area (Guiyu, Guangdong) tri-hexa BDE comparable to USA hepta-deca BDE very elevated median sumbde: 600 ng/g lw; BDE 209: 310 ng/g lw* also elevated in nearby area serum, n=47 --Bi et al 2007 decabde production area (Laizhou Bay) residents, not workers mean serum: 613 ng/g lw, BDE ng/g lw* serum + breast milk, n=156 --Jin et al 2009 are there others: e.g., foam or foam recycling? (Stapleton et al found high penta in US foam recyclers) 24

25 These populations may provide a very interesting natural experiment. high exposure decabde: no epidemiology has been done shorter halflife workers and residents designs might include: adult cross-sectional or longitudinal birth cohort Some concerns: co-exposures, particularly in electronics dismantling area? comparable referent groups, feasibility issues 25

26 occupational studies of exposure to penta replacements, e.g., TDCPP? Can we find such groups? Cancer epidemiology is difficult (e.g., long latency) reproductive study? 26