# Presentation: 120333

## Development of the Revised Reference Dose / Risk Assessment

**Annie M. Jarabek**
**National Center for Environmental Assessment**
**U.S. Environmental Protection Agency**

- Perchlorate Stakeholders Forum
- Sponsored by the IPSC
- Henderson, NV
- 19-21 May 1998

## Outline

- EPA risk assessment guidelines
- NCEA perchlorate toxicity assessment team
- Revised RfD / risk assessment process

## Recommended Studies

- 90-Day subchronic bioassay
- Developmental neurotoxicity study
- Genotoxicity assays
- Mechanistic studies
- ADME -	Absorption, Distribution,            		Metabolism and Elimination
- Developmental study
- 2-Generation reproductive toxicity study
- Immunotoxicity

## EPA Risk Assessment Guidelines

- Principles and procedures to frame the conduct of risk assessments
- Promote consistency and technical quality of scientific inferences
- Flexible, full consideration to all relevant scientific information case-by-case
- Revised as experience and scientific consensus evolve

## EPA Risk Assessment Guidelines

- Developmental toxicity  (1991)                     FR 56(234):  63798 - 63826
- Reproductive toxicity  (1997)                                   EPA No. EPA/630/R-96/009a                   NTIS PB97-100093
- Neurotoxicity  (1998)                                              EPA No. EPA/630/R-95/001Fa                 NTIS PB98-117831
- Thyroid follicular cell tumors (1998)             EPA/630/R-97-002

## EPA Risk Assessment Guidelines

- Proposed revision to carcinogenicity  (1996) EPA/600/P-92/003C                                 NTIS PB96-157599
- Exposure  (1992)                                           FR 57 (104):  22888 - 22938
- Chemical mixtures  (1986)  / Proposed 1998

## Guidelines Available 	

- http://www.epa.gov/ncea
- EPA ORD publications, Technology Transfer and Support Division, NRML Phone:  513.569.7562;   FAX:  513.569.7566.  Need the EPA No.
- National Technical Information Service (NTIS):  703.487.4650;  FAX:  703.321.8547.  Need the NTIS PB No.

## NCEA Perchlorate Toxicity Risk Assessment Team

- Harlal Choudhury	NCEA		general toxicology / risk assessment
- Eric Clegg		NCEA		reproductive toxicology
- Kevin Crofton		NHEERL	neurotoxicology
- Vicki Dellarco		OW		genetic toxicology
- Annie Jarabek		NCEA		general toxicology / dosimetry / risk 						assessment
- Gary Kimmel		NCEA		developmental toxicology
- MaryJane Selgrade	NHEERL	immunotoxicology

## Toxicity Study Review and Revised RfD / Risk Assessment

**Review of existing and new toxicity data**
**Hazard identification**
**Dose-response evaluation**
**Designation of effect levels (mathematical modeling or NOAEL / LOAEL procedure)**
**UF assignment**
**Uncertainty characterization - confidence statements**

## Revised RfD / Risk AssessmentReview Process

- Internal peer review (September 1998)
- External peer review (October 1998)
- Response / revisions subsequent to external peer review (November 1998)
- Submit final revised RfD / risk assessment to Integrated Risk Information System (IRIS) process
- Refine as required with new data

## Future Applications of Revised RfD

- Basis for various guidance levels (e.g., Health Advisory, NPDWR, Superfund remediation goals)
- Converted through the use of standard ingestion and body weight parameters (e.g., 2 L / day and 70 kg for adult)

## Data

**Compliance**

**Health or**
**Eco Risk**

**Regulatory****Standard**

**Sources**

**Treatment**
**Technology**

**Transport**
**Fate**

**Dose**

**Exposure**

**Water Quality**

**Response**

**Data**

## Annie M. Jarabek

- National Center for Environmental Assessment
- (MD-52)
- U.S. EPA
- Research Triangle Park, NC  27711
- Phone:	919.541.4847
- FAX:		919.541.1818
- E-mail:  jarabek.annie@epa.gov