LHP 03-2010 DRAFT ARA Workshop I 1

Break-out Group B

• #5: Formaldehyde

• #12: IEUBK/Pb

• #26: Acrylamide

• Recommended all go forward (with funding considerations)

LHP 03-2010 DRAFT ARA Workshop I 2

Group B Participants

Nathalie Foronda (NZ)Kip Haney (TCEQ): ChairLindsey Jones (TCEQ): Ass’t rapporteurJerry Merski (Altria Client Services)Martha Moore (NCTR)Lynn Pottenger (Dow): RapporteurBob Tardiff (Sapphire)Kimberly Wise (API)Tong Zhou (FDA)[Harvey Clewell][Thomas Dydek][Suneeta Mahagaokar]

LHP 03-2010 DRAFT ARA Workshop I 3

#5: Formaldehyde• Problem Formulation: HPV chemical with widely dispersive exposure:

inhalation exposure focused on health-based risk estimates for toxicity/cancer (rats-nasal tumors; humans-respiratory tract tumors)

• Methodology: Highly developed/detailed MOA (Pathophysiology process: cytotoxicity/cell proliferation-regeneration/hyperplasia/tumors), applies BBDR approach to quantify risk (integrates broad amount of data: cell proliferation rates, mutation rates, cross-links, etc.); need to incorporate genomic data & oncogene/tumor suppressor gene mutation data on p53/K-ras; Could address the following issues:– includes endogenous/background exposure and background processes; – address uncertainty and variability issues; – cross-species extrapolation (rats to humans); – test low-dose linearity proposal of SB; – incorporation of chemical-specific data; – address how much data is enough to depart from default.

• Team: The Hamner/EPA folk plus Bruce Allen; Biologist: Barb Parsons, NCTR( ?), LHP (?); pathologist/cancer expertise (?); regulatory: Kip Chaney (TCEQ), EPA/IRIS Chemical Mgr (?); [Exposure expert (to address human exposure?)]

LHP 03-2010 DRAFT ARA Workshop I 4

#12: IEUBK & Pb

• Problem Formulation: Predict blood level in children exposed by various media (air, soil, food, etc.); (Literature review: Determine if current ‘level of concern’ (0.48 mmole/L) is appropriate); [this model can be used to evaluate soil clean-up targets]

• Methodology: IEUBK model (both child and adult versions exist), developed specifically for lead, is actively used by USEPA & states: translates environmental sources of lead exposure into internal dose (blood lead level); could address the following issues:– incorporates background exposure in model predictions of dose-metrics (SB

issue); – assess variability in exposure using distributions (e.g., dietary, water) (SB

issue); – (lit review may help address low-dose linearity issue; SB issue)

• Team: NZ Ministry of Health: Toxicology (N. Foronda); Public Health Physician (D. Read); Massey U. Epidemiologist (B. Borman); Modeller (TBD?)

LHP 03-2010 DRAFT ARA Workshop I 5

#26: Acrylamide• Problem Formulation: HPV chemical with widely dispersive exposure, including

diet: focus on oral exposure and developing MOA-based health-based risk estimates for cancer (rats- thyroid [& other] tumors; mouse-skin & lung tumors; humans-no specific target; epi data negative)

• Methodology: Develop MOA approach based on WOE, based on acrylamide and its metabolite glycidamide; apply PBPK and BBDR approaches to understand the shape of the low dose dose-response curve; eventually use to quantify low dose risk; consider & incorporate new data from NCTR bioassays & MOA data (plan to use exposure characterized by JECFA); Could address the following issues:

– includes endogenous/background exposure and background processes (mutation); – address uncertainty and variability issues; – cross-species extrapolation (rats and mice to humans); – test low-dose linearity proposal of SB; – incorporation of chemical-specific data (lots of new data); – application of MOA based on WOE;– address how much data is enough to depart from default.

• Timeframe: Target completion in timeframe (may be challenge given new data & differing views)

• Team: Bob Tardiff (Sapphire); M. Leigh Carson (Sapphire); Martha Moore (NCTR); Fred Beland (NCTR); Dan Doerge (NCTR); John Young (ret. NCTR); Lynne Haber (TERA); Errol Zeiger (consultant); David Gaylor (consultant); Sarah Henry (CFSAN) (?); Tong Zhou (FDA); TCEQ or other state rep?