Sixty-day bioassays of
iodinated glycerol,
trichlorfon, and
acetaminophen were conducted using a
leukemia transplant model in 6- to 8-week-old F344 rats to investigate the potential of these chemicals to affect
tumor progression. The chemicals were administered in the
drinking water at doses that approximated those used in previously conducted 2-year
carcinogenesis studies. Simultaneous with dose administration, half of a group of young, healthy, syngeneic rats were given subcutaneous transplants of mononuclear cells derived from spleens of leukemic donors. Variables used to quantitate
tumor progression included
body weight, spleen weight, white blood cell (WBC) and red blood cell (RBC) counts, packed cell volume,
hemoglobin concentration, and platelet counts.
Iodinated glycerol at 1.25 or 2.5 mg/ml caused a greater increase in
leukocytosis in dosed transplant recipients in comparison to that experienced by undosed recipients:
trichlorfon at 2.5 or 5.0 mg/ml enhanced
splenomegaly and induced greater reductions in RBC parameters in dosed recipients in comparison to that experienced by undosed recipients.
Acetaminophen at 3.0 and 6.0 mg/ml resulted in insignificant but dose-related increases in spleen weight and
leukocytosis only in the female rat transplant recipients, as was observed in 2-year studies. Based on results from the short-term
leukemia transplant model, data from 2-year carcinogenicity studies, and structure-activity considerations, exposure to
iodinated glycerol and
trichlorfon was more strongly associated with the expression of
leukemia than exposure to
acetaminophen. The potential carcinogenicity of each of these chemicals should be taken into consideration when calculating estimates of risk and decisions for their use.