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Updated: Aug 8, 2026
In vitro Cell Culture Model for Toxic Inhaled Chemical Testing
Published on: May 8, 2014
A review of perchloroethylene and rat mononuclear cell leukemia
1Cranford Path Ltd., Knutsford, Cheshire, UK.
Abstract:
Mononuclear cell leukemia (MNCL) is an extremely common spontaneous disease of ageing F344 rats accompanied by splenomegaly, anemia, thrombocytopenia, and leukemic infiltration (initially of the spleen, liver, and lung). Rare in other rat strains, incidence in F344 rats is variable, has been increasing, and can exceed 70% in controls. MNCL cells possess natural killer (NK) cell characteristics and apparently, the neoplastic cells derive from large granular lymphocytes (LGL), hence the alternative name of LGL leukemia. LGL leukemia is uncommon in man and occurs in two forms: T-LGL leukemia which has a chronic course, and the much rarer NK-LGL leukemia. In addition to cell type, the latter resembles F344 LGL leukemia being acute in course and involving more pronounced splenomegaly and thrombocytopenia. Chemically related increases in MNCL in F344 rats have not been associated with induction of human LGL leukemia. Carcinogenicity studies of perchloroethylene (PERC) in several rat strains have shown moderate, not clearly dose-related, increases in MNCL only in F344 rats (two studies). There was no consistent decrease in latency and the incidence in the PERC treated groups is within the overall control range. As a response in a rat strain highly predisposed to developing MNCL, these results are not considered predictive for human cancer risk.
Insights
Mononuclear cell leukemia (MNCL) in F344 rats, a common aging disease, showed no clear link to perchloroethylene (PERC) exposure. These findings in a predisposed rat strain do not predict human cancer risk from PERC.
Area of Science:
- Veterinary Pathology
- Toxicology
- Oncology
Background:
- Mononuclear cell leukemia (MNCL), also known as large granular lymphocyte (LGL) leukemia, is a common spontaneous disease in aging F344 rats.
- This leukemia is characterized by splenomegaly, anemia, thrombocytopenia, and leukemic infiltration of organs like the spleen, liver, and lung.
- While rare in other strains, MNCL incidence in F344 rats is variable and can exceed 70% in controls.
Purpose of the Study:
- To investigate the potential carcinogenicity of perchloroethylene (PERC) in relation to Mononuclear Cell Leukemia (MNCL) in F344 rats.
- To assess whether observed increases in MNCL in F344 rats exposed to PERC are predictive of human cancer risk.
Main Methods:
- Carcinogenicity studies were conducted using multiple rat strains, including F344 rats, exposed to perchloroethylene (PERC).
- Incidence, dose-response relationships, and latency of MNCL were analyzed in PERC-treated groups compared to control groups.
Main Results:
- Moderate, not clearly dose-related, increases in MNCL were observed exclusively in F344 rats across two studies.
- No consistent decrease in latency was noted, and the incidence rates in PERC-treated groups remained within the overall control range.
- These results indicate that the increases in MNCL were a strain-specific response in rats highly predisposed to the disease.
Conclusions:
- The observed increases in MNCL in F344 rats exposed to PERC are considered a spontaneous, strain-specific response.
- These findings are not considered predictive of human cancer risk associated with perchloroethylene exposure.
- Further research may be needed to understand the mechanisms of MNCL in F344 rats and its relevance to human health.
