This draft report provides an overview of the types of mechanisms underlying the lymphohematopoietic cancers induced by chemical agents and radiation in humans, with a primary emphasis on leukemia and leukemia-inducing agents. It focuses on how mechanistic information on human leukemia-inducing agents can inform risk assessment.

Lymphohematopoietic neoplasias represent a heterogeneous group of clonal hematopoietic and lymphoid cell disorders and are one of the most common types of cancer induced by environmental and therapeutic agents. It is widely recognized that lymphohematopoietic neoplasms originate through multi-step processes involving a series of genetic and epigenetic alterations that transform a normal hematopoietic or lymphoid cell into a malignant tumor. Following a brief discussion of hematopoiesis and leukemogenesis in the report, a review of the major classes of leukemia-inducing agents—radiation, chemotherapeutic alkylating agents, and topoisomerase II inhibitors—is presented along with information on the mechanisms by which these leukemias occur. This information is then compared with similar information for selected environmental and occupational leukemia-inducing agents.

Following external peer review and public comment, the final report will be posted to the EPA Web site.

U.S. EPA. Lymphohematopoietic Cancers Induced by Chemicals and Other Agents: Overview and Implications for Risk Assessment (External Review Draft). U.S. Environmental Protection Agency, Washington, DC, EPA/600/R-10/095A, 2010.

Comments on the assessment 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-2010-0991" (for the docket ID) to comment on this report.