Biomedical Engineering Reference
In-Depth Information
allow for an accurate estimate of the actual dose of MeOH consumed by
the rats in drinking water. Total water consumption was measured only
weekly, rather than daily, per cage, where multiple rats were housed,
which may inappropriately average individual variability. The classifi-
cation of the results made their interpretation difficult, as the diagnostic
terms used did not match standard pathological guidelines. Of the
classifications made by the pathologists at the Ramazzini Foundation,
nearly half did not match those reviewed by the National Toxicology
Program (NTP, 2004). There were also discrepancies with the study's
control data in comparison to historical control data, where the inci-
dences of total cancers derived from blood-forming cells were con-
sistently approximately four times higher. Furthermore, their report
neglected to acknowledge the high incidence of early mortality (
>
80%
of rats in study) and lung pathologies present in nearly all dose groups,
which likely contributed to the formation of the reported lympho-
immunoblastic lymphomas. Additionally, the report lacked pertinent
information that could help the interpretation of results, such as the
aforementioned limited data on water consumption and limited infor-
mation concerning lung pathology. These limitations diminished the
validity of the study, and its results would require replication to
corroborate the conclusions made in the report. One additional report
in the literature is a graduate thesis examining the carcinogenic poten-
tial of malonaldehyde in Swiss Webster Mice, in which MeOH was
utilized as a vehicle control, although unfortunately there were no
concurrent untreated controls in this study (Apaja, 1980). Mice were
exposed to MeOH in drinking water at doses of approximately 550,
1000, or 2000mg/kg/day six times per week until their spontaneous
death. The incidence of malignant lymphomas in MeOH-treated mice
was higher than the overall incidence in historical controls for high-dose
females and mid-dose males, but the author concluded that these
incidences were “within the normal range of occurrence of malignant
lymphomas in Eppley Swiss mice.” The mouse colony was not main-
tained under specific pathogen-free (SPF) conditions, and there was a
high incidence of pneumonia reported (8-28%), which may be a
confounding variable.
