Interpretation of male rat renal tubule tumors

Journal Article · Wed Dec 01 04:00:00 EST 1993 · Environmental Health Perspectives

DOI:https://doi.org/10.1289/ehp.93101s645· OSTI ID:478934

Rodgers, I S; Baetcke, K P ^[1]

---

1. Environmental Protection Agency, Washington, DC (United States)

Based on an analysis of recent scientific studies, a Technical Panel of the U.S. Environmental Protection Agency`s (EPA) Risk Assessment Forum recently advised EPA risk assessors against using information on certain male rat renal tubule tumors to assess human risk under conditions specified in a new Forum report. Risk assessment approaches generally assume that chemicals producing tumors in laboratory animals are a potential cancer hazard to humans. For most chemicals, including classical rodent kidney carcinogens such as N-ethyl-N-hydroxyethylnitrosamine, this extrapolation remains appropriate. Some chemicals, however, induce accumulation of {alpha}{sub 2u}-globulin ({alpha}{sub 2u}-g), a low molecular weight protein, in the male rat kidney. The {alpha}{sub 2u}-g accumulation initiates a sequence of events that appears to lead to renal tubule tumor formation. Female rats and other laboratory mammals administered the same chemicals do not accumulate low molecular weight protein in the kidney, and they do not develop renal tubule tumors. Because humans appear to be more like other laboratory animals than like the male rat, in this special situation, the male rat is not a good model for assessing human risk. The Forum report stresses the need for full scrutiny of a substantial set of data to determine when it is reasonable to presume that renal tumors in male rats are linked to a process involving {alpha}{sub 2u}-g accumulation and to select appropriate procedures for estimating human risks under such circumstances. 92 refs.

• Sponsoring Organization: USDOE
• OSTI ID: 478934
• Report Number(s): CONF-9111356--
• Journal Information: Environmental Health Perspectives, Journal Name: Environmental Health Perspectives Journal Issue: Suppl.6 Vol. 101; ISSN EVHPAZ; ISSN 0091-6765
• Country of Publication: United States
• Language: English

Related Subjects

02 PETROLEUM
CARCINOGENESIS
CHRONIC EXPOSURE
HEALTH HAZARDS
KIDNEYS
NEOPLASMS
RATS
RISK ASSESSMENT
SEX DEPENDENCE
TUBULES
UNLEADED GASOLINE