Biomedical Engineering Reference
In-Depth Information
request of the NTP and EPA (NTP & EPA, 2011). Methanol was one of
the five studies reviewed. The PWG reviewed 744 slides from 367 rats
in the methanol study. These slides were from the rats diagnosis by the
original study pathologists to have lymphoma or leukemia, as well as,
animals reported to have ear or bone neoplasm. The PWG reported
fewer lymphoid neoplasms primarily from the respiratory tract as well
as fewer neoplasms in the inner ear and cranium. Chronic inflammation
was noted in the respiratory tract and ear suggesting that respiratory
infections were present. Chronic infection was thought by the PWG to
cause hyperplasia that was misdiagnosed in many cases by the original
study pathologists as malignant neoplasms. In areas where chronic
infection was not seen, the PWG generally agreed with original study
pathologists diagnosis of tumor types, location, and numbers. The PWG
concluded that there were fewer malignant neoplasms than reported by
the original study pathologists. As a result of this review, EPA has
announced that it will not use cancer data from this study in its ongoing
risk assessment of methanol because of the overestimating of cancer
incidence by the original study pathologists (EPA, 2012).
Autolytic changes can also be a problem in interpreting lesions when
animals are not scarified in extremis or at a specific time in the study.
Autolytic changes were also a confounding finding of the NTP (2004) in
theRamazzini Foundation aspartame study and an occasionally precluded
histological diagnosis by the NTP pathologists reviewing the methanol
study (NTP, 2010). In neither the Ramazzini Foundation aspartame study
nor methanol study was all the study data available for review by the
working group. Ward and Alden (2009) questioned the qualification and
accuracies of the pathologist diagnosis in the Ramazzini Foundation
aspartame study and pointed out that without all the data being available, a
rigorous review for regulatory purposes of the study is controversial.
8.2.1.2 Mice
A study to evaluate the toxicity and carcinogenicity of
malonaldehyde was conducted at the Eppley Institute (Apaja, 1980).
Malonaldehyde (MDA) can only be kept for a short period of time, as it
is unstable and hydroscopic. MDAwas prepared for this study as a dilute
solution which was made more stable than pure MDA, by dissolving
malondialdehyde bis diethylacetal and 6 N HCL in water. Methanol was
