2,3,7,8-Tetrachlorodibenzo-P-Dioxin (TCDD) Dose-Response Studies: Preliminary Literature Search Results and Request for Additional Studies

Abstract

EPA invited the public to comment on the preliminary list of in vivo mammalian dose-response citations for 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD). This list was compiled as a first step in the development of EPA’s response to the National Academy of Sciences comments (NAS, 2006) on the dose-response assessment presented in the Exposure and Human Health Reassessment of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) and Related Compounds (Dioxin Reassessment, EPA, 2003).
The primary objective of the literature search from which this preliminary list is based was to identify peer-reviewed in vivo mammalian dose-response studies for TCDD that have been published since the Dioxin Reassessment (EPA, 2003). This includes in vivo mammalian dose-response of TCDD and epidemiological studies of TCDD. The literature search was conducted using the online National Library of Medicine database, PubMed, and focused on identifying studies published between the year 2000 and October 31, 2008. The literature search was conducted by the U.S. Department of Energy’s Argonne National Laboratory through an Interagency Agreement with the EPA. The literature search strategy explicitly excluded studies addressing: (1) analytical/detection data and cellular screening assays; (2) environmental fate and concentration data; (3) dioxin-like compounds and toxic equivalents; (4) non-mammalian dose-response data; (5) human exposure analyses only, including body burden data; and (6) combustor or incinerator or other facility-related assessments absent primary dose-response data. The EPA is not seeking submissions or comments on these types of studies at this time.

The EPA invites your review of this preliminary list of in vivo mammalian dose-response citations for TCDD. At this time the Agency requests that interested parties submit only peer-reviewed, in vivo mammalian dose-response studies for TCDD including epidemiological studies that are absent from this list. The EPA asks that the inputs include full citations and the full publication. Directions for submitting these additional studies for the Agency’s consideration are provided below. These submissions will be used during the conduct of a scientific expert workshop on TCDD dose-response modeling, open to the public, to be held in Cincinnati, Ohio on February 18-20, 2009 (to be announced in a future Federal Register Notice).

Two additional citation lists are being provided here for convenience. First, the EPA is providing a list of citations relevant to dose-response assessment that were published in Part II (all citations) and Part III of the 2003 draft Dioxin Reassessment (all citations). Second, the EPA also is providing a preliminary list of supporting references published since the release of the 2003 Dioxin Reassessment pertaining to studies of TCDD kinetic data, TCDD mode-of-action, in vitro TCDD studies, and TCDD risk assessment approaches. The EPA is not seeking the submission of additional studies or comments on these types of studies or these two lists at this time.

Impact/Purpose

To get additional information, specifically peer-reviewed TCDD dose-response studies, to EPA.

Status

An expert workshop on TCDD dose-response modeling, open to the public, to be held in Cincinnati, Ohio on February 18-20, 2009 (to be announced in a future Federal Register Notice).

Citation

U.S. EPA. 2,3,7,8-Tetrachlorodibenzo-P-Dioxin (TCDD) Dose-Response Studies: Preliminary Literature Search Results and Request for Additional Studies. U.S. Environmental Protection Agency, Washington, DC, EPA/600/R-08/119, 2008.

Date	Description
01- 1984	EPA published the Health Risk Assessment Approach for 2,3,7,8-Tetrachlorodibenzo-P-Dioxin.
02- 1994	EPA released the draft documents, Health Assessment Document for 2,3,7,8-Tetrachlorodibenzo-P-Dioxin (TCDD) and Related Compounds Volume (1 of 3), Health Assessment Document for 2,3,7,8-Tetrachlorodibenzo-P-Dioxin (TCDD) and Related Compounds Volume (2 of 3), and the Health Assessment Document for 2,3,7,8-Tetrachlorodibenzo-P-Dioxin (TCDD) and Related Compounds Volume (3 of 3)
03- Sep 1994	EPA launched the Dioxin Exposure Initiative
04- Jul 2000	EPA released the Consolidated Comments from the Peer Review of the Draft Dioxin Reassessment Final Report.
05- Oct 2003	EPA released the NAS Review Draft Dioxin Assessment with updates on the Questions and Answers about Dioxin Web site.
06- Oct 2004	EPA released the NAS Review Draft Dioxin Assessment, in preparation for the first NAS panel review meeting scheduled for 11/22 -23/2004, in Washington, DC.
07- Sep 2008	The Interagency Dioxin Workgroup released updates on the Questions and Answers about Dioxin Web site.

Additional Information

Comments on this prelimary list may be submitted and reviewed using the e-Government Regulations.gov web site. From the site, select Environmental Protection Agency and the keyword EPA-HQ-ORD-2008-0789 (for the docket ID).

• Preliminary Reference List for 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) In Vivo Mammalian Dose-Response and Epidemiological Studies (PDF)  (48  pp, 162.1 KB, about PDF)
• Draft Selection Criteria (PDF)  (1  pp, 60.5 KB, about PDF)
• Charge to External Reviewers (PDF)  (3  pp, 17.6 KB, about PDF)
• Workshop Registration, Agenda and links with information

Related Link(s)

• Preliminary Supporting Reference List for 2,3,7,8-Tetrachlorodibenzo p dioxin (TCDD) ModeMechanism Of Action, Toxicokinetics, In Vitro Study Data, Modeling-Methodology (PDF)  (81  pp, 262.7 KB, about PDF)
• Reference Citations From Exposure and Human Health Reassessment of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) and Related Compounds (PDF)  (189  pp, 484.4 KB, about PDF)
• EPA, 2003. Exposure and Human Health Reassessment of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) and Related Compounds
• NAS, 2006. National Academy of Sciences Health Risks from Dioxin and Related Compounds: Evaluation of the EPA Reassessment