Older Adults’ Exposures: To What and Pathways

1. Older Adults’ Exposures: To What and Pathways Larry L. Needham, Ph.D. Chief, Toxicology Branch National Center for Environmental Health Centers for Disease Control and Prevention Atlanta, GA USA 30341

2. Inhalation Ingestion Dermal Contact Exposure Pathway Source Water, Air, Food, Soil, Dust, Sediment, Personal Care Products Exposure Dose Absorption following: Internal Dose Metabolism Distribution Elimination Target Organ Dose Elimination Biologically Effective Dose Effect

3. Biomonitoring Assessment of internal dose by measuring the parent chemical (or its metabolite or reaction product) in human blood, urine, milk, saliva, adipose, or other tissue.

4. CDC’s Second National Report on Human Exposure – data from NHANES 1999-2000 Urine Metals (13) PAH metabolites Phthalate metabolites Pesticides Organophosphorus Carbamates Herbicides Repellants Phytoestrogens Blood Lead Cadmium Mercury Serum Dioxins Furans PCBs Organochlorine pesticides Cotinine Released: March 2003 www.cdc.gov/exposurereport

5. National Report on Human Exposureto Environmental Chemicals What it is: An ongoing (every 2 years) biomonitoring assessment of the exposure of the U.S. population to selected environmental chemicals Matrices monitored: Urine; blood and its components

6. Major Findings: U.S. Population-based Reference Ranges • Geometric means • 10th, 25th, 50th, 75th, 90th, and 95th percentiles • Age, sex, race/ethnicity breakout

7. Goals of National Report • Assess exposure to various chemicals (which?) • Establish national “reference ranges” of these chemicals (blood, urine) • Track, over time, trends in these “reference ranges” • Help set priorities on linking exposure to health outcomes In American population and subpopulations (age, sex, race/ethnicity)

8. Uses of National Report Source Exposure Effects • Assess effectiveness of efforts to reduce exposures (lead in gasoline; FQPA; POPs) in all Americans • In some cases, provide data for establishing source (pattern recognition, e.g., gasoline, dioxins/furans) • Provide data for risk assessment (dose-response and exposure assessment) • Provide data for linking environmental exposure data with interactions with genes, nutrition, and demographic data to eventually link with health outcome data

9. Interpreting Data in the Report • The presence of a chemical in the body does not mean it causes disease • For many chemicals in the Report, more research is needed to interpret these levels • The Report provides new exposure data, but does not identify levels that cause disease • Additional studies are needed

10. Other Uses of Biomonitoring Data • Clinical studies • Epidemiological studies (National Children’s Centers, NCS) • Occupational studies • Emergency investigations

11. Pharmacokinetics of Environmental Chemicals in Body and Matrices Available for Analyses Ingestion Inhalation Dermal Gastrointestinal Tract Primary Deposition Sites Lung Fat Bone Liver Blood/Lymph Portal Blood Secretory Structures Soft Tissues Bile Alveoli Kidney Tears Secretions Feces ExpiredAir Saliva Sweat Milk Urine Bladder Needham et al. Neurotoxicology 2005 (online) Rozman & Klaassen in Casarett & Doull’s Toxicology. The Basic Science of Poisons, 5th Edition 1996 p 91.

12. Blood Toxicant/Metabolite Hemoglobin Adduct Concentration Albumin Adduct DNA Adduct Urinary Adduct Urinary Metabolite 1 10 100 1000 Time (Days) Post-Exposure Fate of a Persistent Chemical in Blood and Urine Needham and Sexton, JEAEE 10:611-629 (2000)

13. Blood Toxicant/Metabolite Urinary Metabolite Albumin Adduct Concentration Hemoglobin Adduct DNA Adduct Urinary Adduct 1 10 100 1000 Time (Days) Post-Exposure Fate of a Nonpersistent Chemical in Blood and Urine Needham and Sexton, JEAEE 10:611-629 (2000)

14. Persistent Chemicals • Polychlorinated Biphenyls (PCBs) • DDT → DDE • Perfluorinated Chemicals • Lead Non Persistent Chemicals • Chlorpyrifos → Trichloropyridinol (TCPy) • Nicotine → Cotinine

15. Characteristics of Persistent Organic Pollutants • Persist in environment • Bioaccumulate through food chain (lipophilic) • Pose risk of causing adverse effects humans/environment • Long range transport

16. Stockholm Convention on POPs Global treaty to protect human health and the environment from POPs. Aldrin Dieldrin Endrin Chlordane Heptachlor Toxaphene DDT Mirex Hexachlorobenzene PCBs Dioxins Furans

17. y x Persistent Organic Pollutant: PCBs • 209 congeners • Production stopped 1977 • Primary route of exposure; ingestion (certain foods) • Indoor air (older electrical devices; fluorescent lights contain PCB-filled capacitors; caulking materials) x and y = Cl N ( x + y ) = 1-10

18. MA 95th MA 50th NHB 95th NHB 50th NHW 95th NHW 50th 50th & 95th Percentile of PCB 138 by Age Group, Race & Sex Ng/g Male Female Male Female Male Female Male Female 12-19 20-39 40-59 60+

19. Cl Cl C Cl H C Cl C Cl Cl C Cl Cl DDT DDE Cl Persistent Organic Pollutant: p,p’ - DDT • DDT use was banned in U.S. 1973 • Agriculture and malaria control

20. MA 95th MA 50th NHB 95th NHB 50th NHW 95th NHW 50th 50th & 95th Percentile of DDE by Age Group, Race & Sex Ng/g Male Female Male Female Male Female Male Female 12-19 20-39 40-59 60+

21. Second Report Results • DDT banned in U.S. in 1973 • Pesticide DDE is 3 times higher in Mexican-Americans (3.9; 1.6; 1.3 ng/g) • Also measurable in 12-19 year olds (born after ban) (0.6 vs. 1.8 ng/g) • May be persisting in environment or from imported food

22. Perfluorochemicals (PFCs) in the Environment • Produced since 1950's for use in: • Surface treatments: soil and stain resistant coatings on textiles, carpet, leather • Paper protection: provides oil, grease and water resistance on paper products including those for food use • Performance chemicals including insecticide, fire fighting foams, industrial surfactants, acid mist suppression • 3M phased out its fluorochemistry in May 2000

23. O O O O O CH2CH2OH CH2CH2COOH H OH N N N C S S S S CF3(CF2)7 CF3(CF2)n CF3(CF2)7 CF3(CF2)7 CF3(CF2)n OH R R R O O O O Perfluorinated Chemicals Sulfonic acids (e.g., PFOS) Sulfonamides Carboxylic acids (e.g., PFOA)

24. Serum Pools: NHANES 2001/2002 • 34 People per pool (Total 1,734 people; 51 pools) • Unweighted; used for estimates of the “means” • 0.75mL Serum per person • 25.5 g Serum per pool • 2 g BFRs/PCBs/Persistent Pesticides • 22 g PCDDs/PCDFs/cPCBs • 0.5 g Total Lipids • 0.4 g Perfluorinated chemicals

25. NHANES 2001-2002 Pools ( ) for perfluorinated chemicals

26. Mean and Range of PFOS by Age Group, Race and Sex

27. Mean and Range of PFOA by Age Group, Race and Sex

28. Mean and Range of TEQs by Age Group, Race and Sex

29. Lead Blood lead levels (BLLs) 1 year of age and greater

30. Lead Used in Gasoline Declined from 1976 Through 1980 110 100 90 80 Gasoline lead Lead used In gasoline (1000 tons) 70 60 50 40 30 1975 1976 1977 1978 1979 1980 1981 Year

31. Predicted Blood Lead Changes with Decreasing Gasoline Lead 110 17 Predicted blood lead 100 16 90 15 14 80 Lead used in Gasoline lead gasoline Mean blood 13 70 lead levels (thousands (  g/dL) 12 of tons) 60 11 50 10 40 9 30 1975 1976 1977 1978 1979 1980 1981 Year

32. 110 17 Predicted blood lead 100 16 90 15 14 80 Lead used in Gasoline lead gasoline Mean blood 13 70 lead levels (thousands (  g/dL) 12 of tons) 60 11 50 Observed blood lead 10 40 9 30 1975 1976 1977 1978 1979 1980 1981 Year NHANES II Blood Lead Measurements Found A Substantial Decline in Blood Lead Levels,10 Times More Than Predicted from Environmental Modeling

33. 18 100 16 14 80 12 60 Lead used In gasoline (1000 tons) Blood lead 10 Blood lead levels (mg/dL) Gasoline lead 40 8 6 20 4 0 2 1974 1976 1978 1980 1982 1984 1986 1988 1990 1992 Year After NHANES II, EPA Further Restricted Leaded Gasoline and Gasoline Lead Levels Continued to Decline Through 1991

34. 18 100 16 14 80 12 60 Lead used In gasoline (1000 tons) Blood lead 10 Blood lead levels (mg/dL) Gasoline lead 40 8 6 20 4 0 2 1974 1976 1978 1980 1982 1984 1986 1988 1990 1992 Year NHANES III (1988-1994) Showed Blood Lead Levels Continued to Decrease as Gasoline Levels Declined

35. 18 16 14 12 10 Blood lead levels (mg/dL) 8 6 4 2 0 1974 1976 1978 1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 Year Blood Lead Levels in the U.S. Population 1976 -2000NHANES II, III, 1999-2000

36. Major Findings: Decline in Blood Lead Levels among Children For children 1 through 5 years old • NHANES III (1991-94) • Geometric mean BLL 2.7 g/dL • 4.4% had BLLs  10 g/dL • NHANES 1999-2000 • Geometric mean BLL 2.23 g/dL • 2.2% had BLLs ≥ 10 g/dL • Higher prevalence of BLLs in U.S. children occur in urban settings, lower SES, immigrants and refugees (Geltman et al., 2001)

37. Chlorpyrifos • Organophosphorus pesticide • Many food uses • Termiticide • Use in and around homes and non-residential settings - eliminated

38. Cl Cl Cl Cl O S Cl Cl O O P P OR’ OR’ N N OR’ OR’ Cl Cl Cl OH N + + S O HO HO P P OR’ OR’ 3,5,6-TCPy OR’ OR’ Limitation: Specificity of Analysis Chlorpyrifos (R’=ethyl) and Chlorpyrifos-methyl (R’=methyl) Metabolism and Env’l Degradation 3,5,6-TCPy is “specific” metabolite Dialkyl phosphates are “nonspecific” metabolites

39. MA 95th MA 50th NHB 95th NHB 50th NHW 95th NHW 50th 50th & 95th Percentile of 3,5,6-TCPy by Age Group, Race & Sex µg/L Male Female Male Female Male Female Male Female 6-11 12-19 20-39 40-59

40. O N CH3 N Cotinine • Nicotine metabolite that tracks exposure to tobacco smoke • For nonsmokers, tracks exposure to secondhand smoke

41. 5 4 3 2 1 0 0.1 1.0 10 100 1000 Exposure of the U.S. Population to Tobacco Smoke: Serum Cotinine Levels (NHANES III, 1988-1991) ETS exposure (nonsmokers) Smokers Percentage of the population Serum cotinine (ng/mL)

42. Second Report Results • Decrease in ETS 1988-1991 to 1999-2000 • Measured as serum cotinine • Children: 58% decreased • Adolescents: 55% decreased • Adults: 75% decreased

43. MA 95th MA 50th NHB 95th NHB 50th NHW 95th NHW 50th 50th & 95th Percentile of Cotinine by Age Group, Race & Sex Ng/mL 3-11 12-19 20-39 40-59 60+

44. Third National Report on Human Exposure to Environmental Chemicals Includes chemicals from Second National Report (1999-2000) + the following in NHANES 2001-2002 • Organochlorine pesticides: aldrin, dieldrin, endrin • OP pesticides: additional metabolites • Pyrethroids: 5 metabolites • Herbicides: mercapturate metabolites of acetochlor and metolachlor • PAHs: 1-, 2-, and 4-hydroxychrysene; 4- and 9-hydroxyphenanthrene; 9-hydroxyfluorene; 3-hydroxybenzo(a)pyrene • Additional PCDDs and PCBs • Additional phthalate metabolites (e.g., oxidative metabolites of DEHP and DnOP)