Exposure Modeling. Interpretation of biomonitoring data using physiologically based pharmacokinetic modeling. Centers for Human Health Assessment

Transcription

1 Exposure Modeling Interpretation of biomonitoring data using physiologically based pharmacokinetic modeling Centers for Human Health Assessment September 25-29, 2006

2 Exposure assessment Emission Inhalation Skin absorption Ingestion Source Environmental monitoring/modeling Activity diary or questionnaire Transport & Transformation Soil Exposure modeling Indirect approaches Dose/contact rate Simulation of exposure scenarios Point-of-contact measurement Direct approaches PBPK modeling Biomonitoring

3 Characterizing exposure pattern is important when interpreting biomonitoring data Biomarker levels are determined by both pharmacokinetics and exposure patterns. Pharmacokinetics variability Exposure patterns variability (true interindividual differences) + uncertainty (possible errors in estimating the true values) Parameter sensitivity Exposure models simulate: Sources Routes Duration Frequency Intensity A very important component: Human behaviors and activities

4 Modeling human behaviors & activities Human behavior flows from three main sources: desire, emotion, and knowledge. Plato Human behavior is the collection of activities performed by human beings and influenced by culture, attitudes, emotions, values, authority, rapport, hypnosis, persuasion, and/or coercion. Two things are infinite: the universe and human stupidity; and I m not sure about the universe. Albert Einstein

5 Maybe Einstein was right

6 Model structure and parameters What are you simulating? Household vs. occupational exposures Children vs. adult exposures The balance between the representation of the model to reality and the complexity/manageability of the model. People are exposed to PCB through food (fish, duck, turtle, frog, etc.) and water, air, skin contact (dust particles), products that contain PCBs (additives in paints, inks, electrical equipments, etc.), and exposure in wombs and breast milk. Will you include all these exposures in your model?

7 Tools and Models

8 OECD s database on chemical risk assessment models ( A searchable database that includes information on models which predict health or environmental effects, exposure potential and possible risk. Physical-chemical properties Environmental fate properties Human health hazard Human health exposure/risk: types of exposure Human health exposure/risk: routes of exposure Environmental hazard Environmental exposure/risk: biota exposed Environmental exposure/risk: exposure pathways

9 US EPA Exposure Assessment Tools and Models ( Rank chemicals of concern Data availability Estimate release and exposure potential Simulate the exposure scenarios of concern

10 US EPA Exposure Assessment Tools and Models Estimation Program Interface (EPI) Suite estimates physical/chemical properties, environmental fate and transport. Pesticide Inert Risk Assessment Tool estimates exposure/risk resulting from contact with pesticides used in the home. Wall Paint Exposure Assessment Model (WPEM) estimates exposure to the chemicals emitted from wall paint. Multi-Chamber Concentration And Exposure Model (MCCEM) estimates average and peak indoor air concentrations of chemicals released from products or materials in houses, apartments, townhouses, or other residences.

11 Compartment models (McKone, 1987) (Kim et al., 2004)

12 Multi-media mass transfer models (Howard-Reed et al., 1999) (Little and Chiu, 1998) (Howard and Corsi, 1998)

13 Useful links on the US EPA website (

14 Useful links on the US EPA website (

15 Aggregate & Cumulative exposures Sources of exposure Routes of exposure Ingestion Organophosphate Inhalation Skin absorption AChE Carbamate Aggregate Exposure Exposure to one chemical from multiple sources & multiple routes Cumulative Exposure Exposure to multiple chemicals from a common-mechanism group

16 Modeling aggregate & cumulative exposures Calendex TM ( Calendar-based system used to estimate distribution of exposure Cumulative and Aggregate Risk Evaluation System (CARES TM ) ( Within-day (minute by minute) exposures Dietary Exposure Potential Model ( LifeLine TM v4.3 ( Modeling a person s lifetime exposure

17 Databases US EPA s Human Exposure Database System (HEDS) contains chemical measurements, questionnaire responses, documents, and other exposure-related information. US EPA ORD (1996). Descriptive statistics tables from a detailed analysis of the National Human Activity Pattern Survey (NHAPS) data. US EPA Office of Water (2000). Estimated per capita water ingestion in the United States: Based on data collected by the United States Department of Agriculture s Continuing Survey of Food Intakes by Individual. US EPA s Consolidated Human Activities Database (CHAD).

18 CHAD CHAD contains databases from previously existing human activity pattern studies. Original raw data database Data modified according to predefined format requirements application The purpose of CHAD is typically used to provide input data for exposure modeling or PBPK modeling

19 Types of data in the CHAD database From CHAD s User Guide

20 CHAD diary location code

21 CHAD diary activity code

22 Linking exposure modeling with PBPK modeling

23 Linking the exposure models to a PBPK model example of chloroform Household exposure to chloroform: Drinking tap water, hot beverage, and soft drinks Inhaling and exposing through skin in shower/bath Inhaling indoor air that contains chloroform from outdoor sources Inhaling indoor air that contains chloroform from indoor sources Washing hands Using dishwasher Using washer Flushing toilets Using bleach Simulating household exposure to chloroform: Drinking tap water Inhaling and exposing through skin in shower Inhaling chloroform in indoor air

24 Exposure Parameters Time when consume water Time of showering Chloroform concentrations in water Chloroform concentrations in indoor air May or may not be a function of water conc. Drinking water amount Shower duration Shower flow rate Shower stall dimension Mass transfer coefficient Time of sampling (Tan et al., 2006)

25 Shower duration (AWWA Research Foundation And AWWA Residential End Uses of Water )

26 Shower flow rate (AWWA Research Foundation And AWWA Residential End Uses of Water )

27 Simulating chloroform concentrations in blood & exhaled breath with a PBPK model Q W C W,in Chloroform in indoor air Q A C A,in V A C A y Q A C A Lung airspace Lung blood Fat Q w C W,out From Weisel et al. (1999). Developing exposure estimates. In Exposure to Contaminants in Drinking Water (S. S. Olin, ed.) ILSI. Skin Rapidly perfused Slowly perfused Kidney Venous Blood Liver Metabolism

28 Time course PBPK model simulations of chloroform in exhaled breath

29 Time course PBPK model simulations of chloroform in blood

30 Summary Emission Inhalation Skin absorption Ingestion Source Environmental monitoring/modeling Activity diary or questionnaire Transport & Transformation Soil Exposure modeling Indirect approaches Dose/contact rate Simulation of exposure scenarios Point-of-contact measurement Direct approaches PBPK modeling Biomonitoring

31 References Howard and Corsi (1998). Volatilization of chemicals from drinking water to indoor air: the role of residential washing machines. J. Air & Waste Manage. Assoc. 48, Howard-Reed, Corsi, and Moya (1999). Mass transfer of volatile organic compounds from drinking water to indoor air: the role of residential dishwashers. Environ. Sci. Technol. 33, Kim, Little, and Chiu (2004). Estimating exposure to chemical contaminants in drinking water. Environ. Sci. Technol. 38, Little and Chiu (1998). Exposure to contaminant in drinking water: estimating uptake through the skin and by inhalation. ILSI, Risk Science Institute Working Group. Olin Ed. pg. 93. McKone (1987) Human exposure to volatile organic compounds in household tap water: the indoor inhalation pathway. Environ. Sci. Technol. 21, Tan, Liao, Conolly, Blount, Mason, Clewell (2006). Use of a physiologically based pharmacokinetic model to identify exposures consistent with human biomonitoring data for chloroform. J. Toxicol. Environ. Health A 69,