1. Hazardous Exposures of PBDE to Human Health
veritas, probitas, iustitia
Hazardous Exposures of PBDE to Human Health
Bambang Wispriyono, PhD.
International Seminar on Electronic Industrial Waste Management and Waste as Industrial Resources to Support Reducing Releases of PBDEs/UPOPs , Bali, 8-9 Januari 2018

2. Bambang Wispriyono, PhD.
Lecturer Dept. of Env Health, FPHUI/President of EHSA Indonesia)
Pharmacist, Universitas Indonesia (1992) PhD in Environmental Toxicology (Univ. of Occupational and Environmental Health (UOEH), Japan (2001) Postdoctoral fellowship, Department of Occupational and Environmental Health, Wayne State University, Detroit, Michigan USA (2002) Now: Director, Center of Industrial and Environmental Health Studies FPHUI (PKKLI FKMUI) & 2015-Now: President of Environmental Health Specialist Association Indonesia (EHSA Indonesia) 2016-Now: Commissioner/Dewan Pengawas `Water Supply Company (PDAM) Tirta Asasta, Kota Depok 2016-Now: Commissioner/Pengawas of Indonesian Public Health Education Institution (INDOPHEIN/ AIPTKMI) : Executive Director of Indonesian Public Health Education Institution (INDOPHEIN/AIPTKMI) : Dean Faculty of Public Health Universitas Indonesia (FPHUI) : Expert Team and Member of Pesticide Committee, Ministry of Agriculture, Republic of Indnesia Now: Member of Technical Committee on Hazardous Substances, Ministry of Environment and Forestry Republic of Indonesia
International Office - UI

3. Polybrominated Diphenyl Ethers (PBDEs):
PBDE’s Classed as Persistent Organic Pollutants (POP’s)
flame-retardant
209 congeners
1 to 10 bromines
Persistent, bioaccumulative, and structurally similar to PCBs, DDT, and other POPs
Banned in most countries:
Penta BDE
Octa BDE
Deca BDE
Can break down to dioxins, furans, etc which are very similar to known cancer causing and toxic compounds

4. Waste Treatment Plants
How Are We Exposed to Flame Retardants?
Waste Treatment Plants
Work
Environment
Chem Plants
Landfills
Diet
Vehicles
House Dust

5. Human Exposure Breastmilk Maternal transfer to fetus Diet (esp., fish)
Indoor, house & office dust, outdoor air
Occupation

6. Daily U.S. Adult ΣPBDE Intake
Deca BDE detected in peregrine falcon eggs at levels that approach levels that cause permanent brain damage in mammals. Lindberg P, Stellstrom U, Haggberg L and De Wit C, Higher Brominated Diphenyl ethers and Hexabromocyclododecane Found in Eggs of Peregrine Falcons Breeding in Sweden, Environmental Science and Technology, 38(1):

7. Estimates of PBDE daily human intake for different countries.

8. Major Flame Retardant Exposure Pathways
12/4/2018
Major Flame Retardant Exposure Pathways 8

9. Previous Studies on PBDE Exposure
Exposure models had suggested that infants would receive the highest exposure among various age classes due to breast milk ingestion (Jones-Otazo et al., 2005; Schecter et al. 2003)
Studies in US adults have observed significant associations with both
diet (Wu et al., 2007; Fraser et al., 2010) and dust (Johnson et al., 2010)
Fewer studies on children’s exposure:
Rose et al. (2010) reported levels in 2-5 year old children in California and found concentrations 2-50X higher than adults
Windham et al. (2010) measured PBDEs in 6 to 8 year old girls from California and Ohio; significantly higher concentrations in CA vs Ohio; higher in blacks compared to whites
Quiros-Alcala et al. (2011) measured PBDEs in dust from low-income households; concentrations were among highest measured
Zota et al. (2010) wrote perspective article on PBDEs and socio-economic disparities

10. PBDEs Burdens Was found in women’s breast milk
December 4, 2018
PBDEs Burdens
Was found in women’s breast milk
9 samples – range 13 to 156 ppb PBDEs
Median 50 ppb (parts per billion)
Japan blood median 1.3 ppb
Swedish breast milk median 2.1 ppb
Texas 2002 – Breast milk from 47 mothers – median 34 ppb
Across U.S breast milk samples – median 58 ppb
ELSI - 2/10/04

11. Trends of Toxin Levels
2 notes from this slide. One is the 100 fold increase in levels in 30 years of PBDEs. The second is the very slow decline in PCB’s and dioxins indicating the slow loss of these highly toxic chemicals.

12. PBDEs in Human Samples From Around the World
1000
100 10
Total PBDEs (ng/g lipid) 1
0.1
1970
1980
1990
2000
2010
From Hites et al., 2005

13. Additional Reports - PBDEs
December 4, 2018
Additional Reports - PBDEs
(adapted from Northwest Environmental Watch, 2004)
ELSI - 2/10/04

14. Correlation Between PBDEs and OH-BDEs (Metabolite of PBDEs)
rs= 0.60
p <0.0001

15. Health Effects of PBDEs:
Hormonal disruption
Animal exposure studies have observed decreases in thyroid hormone levels (Zhou et al., 2001; Tomy et al. 2004)
Associations between PBDEs and thyroid hormones (Turyk et al., 2008; Chevrier et al., 2010) and reduced fecundability (Harley et al., 2010) in human population
Developmental effects
Associations between cryptorchidism and PBDEs in male infants (Main et al., 2007);
Associations between PBDE exposure at birth and neurodevelopment measures in children (Roze et al., 2009; Herbstman et al., 2010)
Liver toxicity
Enzyme Induction
Cytochrome P450s 2B1/2, 3A
UDP-glucuronyl transferase
Toxic to the developing reproductive system
Cancer
The International Agency for Research on Cancer (IARC) has classified
PBDE as a Group 3 carcinogen (not classifiable as to its carcinogenicity to humans) based on inadequate evidence of carcinogenicity in humans and inadequate or limited evidence in experimental animals. The EPA assigns the cancer category Group D (not classifiable as to human carcinogenicity) to mono-, di-, tri-, tetra- , penta-, hexa-,

16. PBDEs are Thyroid Hormone Mimics
PBDE Oxidative Metabolites
Thyroid Hormones
Triiodothyronine (T3)
T3-like OH-BDE
Thyroxine (T4)
T4-like OH-BDE

17. Association Between PBDEs in Pregnant Women and Thyroxine (T4)
rs= 0.19
p <0.05
**Same trend observed for total T4 (rs = 0.20; p<0.05)

18. Observed Relationships between Thyroid Hormones and PBDEs
Cohort
↑TSH
↑FT3/TT3
↑FT4/TT4
Human Studies
USA (n = 297)
Herbstman et al., 2008
No effect
↑BDE 100/BDE 153
USA (n =405)
Turyk et al., 2008
↓BDE 47
↑∑BDEs
USA (n=270)
Chevrier et al., 2010
↓PBDEs NM
USA (n=137)
Stapleton et al., 2011
↓ OH-BDE 49
USA (n=25)
Zota et al., 2011
↑PBDEs/OH-BDEs
Animal Studies
Rats
Zhou et al., 2001
American Kestrels
Fernie et al., 2005
Tomy et al., 2004
Juvenile Lake trout
NM- not measured

19. Why Children are Exposed to Flame Retardants?
Indoor environments are often more polluted than outdoor environments (PBDEs in Dust>>>>>PBDEs in Soils)
Children are spending more time indoors
Children are physically in contact with many FR treated products
Children between the ages of 1-3 years of age are receiving the highest exposure to PBDEs in the world, due to dust exposure and subsequent hand-to-mouth activities
PBDE exposure are higher in minorities and families with lower incomes living in high risk areas

20. Neurodevelopmental Effects Observed in Animal Studies
PBDEs shown to affect development of fetal human neural progenitor cells in vitro which was mediated by thyroid hormone signaling (Schreiber et al. 2010)
Studies conducted in rodent models observed significant alterations in spontaneous behavior and habituation, deficits in learning and memory, and changes in cholinergic nicotinic receptors, primarily occurring when exposure occurs during “rapid brain growth” (Eriksson et al., 2001,2002; Viberg et al., 2003, 2006, 2007).
Mice exposed to BDE 209 during rapid brain growth were observed to have altered expression of CAMKII, GAP-43 and BDNF in different regions of the brain (Viberg et al., 2007).

21. Neurodevelopmental Deficits Associated with PBDEs in Children
(Herbstman et al. 2010)
PBDE levels in cord blood at birth were negatively associated with:
Mental Developmental Index at 24 months of age (BDEs 47, 99,and 100, univariate and adjusted models);
Full and Verbal IQ at 48 months (BDE 47 and 100, adjusted models);
Full and Performance IQ at 72 months (BDE 100 and 153; univariate and adjusted models)

22. Risks to fetus, infants and children
PBDEs cross the placenta
Infants and children more susceptible to most toxins
Blood/brain barrier not fully developed
Intestinal absorption of nutrients and contaminants is greater; e.g. calcium, lead
Skin is more permeable
Hand to mouth activity
Close to the ground- high exposure to dust, carpets
Receive mother’s toxins through breast milk

23. PCBs: PERVASIVE DEVELOPMENTAL EFFECTS
Early Childhood
Memory, attention, verbal ability, information processing
Psychomotor development
Sustained activity, high level play
Withdrawn, depressed behavior
Hyperactivity
Preteen
Word and reading comprehension
Full scale and verbal IQ
Memory and attention
In infancy and early childhood, prenatal PCB exposure is associated with a variety of cognitive impairments (reduced memory and attention, decreased verbal ability, impaired information processing), developmental delays (reduced psychomotor development), and adverse behavioral and emotional effects (decreased sustained activity, decreased high-level play, increased withdrawn and depressed behavior, and increased activity level).(1-7)
In preteen years, prenatal PCB exposure is associated with decreased word and reading comprehension, decreased full-scale and verbal IQ, and reduced memory and attention.(9)
1. Jacobson SW, Fein GG, Jacobson JL, et al. The effect of intrauterine PCB exposure on visual recognition memory. Child Dev Aug;56(4): , 1985.
2. Jacobson JL, Jacobson SW, Humphrey HE. Effects of in utero exposure to polychlorinated biphenyls and related contaminants on cognitive functioning in young children. J Pediatr Jan;116(1):38-45, 1990.
3. Jacobson J. Effects of prenatal PCB exp on cognitive processing efficiency and sustained attention. Dev Psychol 28: , 1992.
4. Gladen BC, Rogan WJ, Hardy P, et al. Development after exposure to polychlorinated biphenyls and dichlorodiphenyl dichloroethene transplacentally and through human milk. J Pediatr Dec;113(6): , 1988.
5. Rogan WJ, Gladen BC. PCBs, DDE, and child development at 18 and 24 months. Ann Epidemiol Aug;1(5): , 1991.
6. Koopman-Esseboom C, Weisglas-Kuperus N, de Ridder MA, et al. Effects of polychlorinated biphenyl/dioxin exposure and feeding type on infants' mental and psychomotor development. Pediatrics May;97(5):700-6, 1996.
7. Patandin S, Lanting CI, Mulder PG, et al. Effects of environmental exposure to polychlorinated biphenyls and dioxins on cognitive abilities in Dutch children at 42 months of age. J Pediatr Jan;134(1):33-41, 1999.
8. Patandin S. Effects of Environmental Exposure to PCBs and Dioxins on Growth and Development in Young Children. A Prospective Follow-Up Study of Breast-Fed and Formula–Fed Infants From Birth Until 42 Months of Age. Thesis, Rotterdam, 1999.
9. Jacobson JL, Jacobson SW. Intellectual impairment in children exposed to polychlorinated biphenyls in utero. N Engl J Med Sep 12;335(11):783-9, 1996.

24. Lowest observed effect levels in PBDE animal toxicity studies.

25. Conclusions In summary,
PBDE toxicity indicate that PBDE exposure in test animals causes a decrease circulating levels of thyroid hormones, leading to hypothyroidism
PBDEs are significantly associated with circulating thyroid hormone levels during pregnancy
Maternal PBDE levels are associated with deficits in birth outcomes (e.g. birth weight and head circumference)
Children have higher body burdens than adults and toddlers may represent the age class with the highest exposure to PBDEs
Exposure to PBDEs occurs during early development
Children and women have a right to a safe, fair, and healthy environment
PBDEs impact on health’s profile and regulation in Indonesia should be formulated by inter-sectoral institutions as well as Ministry of Health, The National Agency of Drug and Food Control (Badan POM), Ministry of Environment, Universities, and others

26. Thank You