Hazard Assessment and Contaminated Sites - Dealing with Contaminated Sites: From Theory Towards Practical Application - page 529

historical control data as an aid to evaluation, only values produced by the identical
methods from the same laboratory are valid in such comparisons. Literature val-
ues for normal ranges that do not specify the method by which they were obtained
should be used with caution.
Sensitivity and specificity of the enzyme changes as diagnostic of organ pathol-
ogy are greatly influenced by the species selected for testing and are of great
importance when specific clinical chemistries are selected for inclusion in toxic-
ity studies. For example, in mammalian species, aspartate transaminase (AST) is
not specific to any tissue and thereby elevated plasma AST activity may suggest
damage to any one of many tissues. In contrast, alanine transaminase (ALT) is rela-
tively specific to the liver in the cat, dog, ferret, mouse, and rat whereas, in primates,
ALT is present in heart, skeletal muscle, and liver.
12.3.5.5 Absolute and Relative Organ Weights
Generally, histopathology is more sensitive for establishing the lowest dose pro-
ducing an effect than organ or body weight changes. Organ weights are usually
reported as absolute organ weights and as relative organ weights (relative to body
weight and/or brain weight). Relative organ weight comparisons are used since body
weights are often affected by contaminant administration.
A proper evaluation will include consideration of any correlation between organ
weights (absolute and relative), histopathological and metabolic/pharmacodynamic
data.
12.3.5.6 Post Mortem Observation
Although much progress has been made in the standardisation of nomenclature,
to minimise any difficulties in this area, an experienced pathologist will describe
each significant lesion type, at least once, in such detail that another competent
pathologist can perceive a mental picture of the lesion and form a judgment as to its
relevance to the histopathology induced by the contaminant being tested.
12.3.5.7 Analysis and Evaluation of Study Parameters in Toxicity Studies
In this section an analysis and evaluation of study parameters in acute, developmen-
tal, reproductive and special toxicity studies is given
Acute Toxicity Studies
Important end-points in acute toxicity studies are clinical signs, gross necropsy
signs, and mortality. Since the purpose of acute toxicity studies has moved away
from the establishment of a strict, quantitative number for the median lethal dose to
an estimate of the likely toxicity range, the emphasis is more on clinical signs and
gross organ pathology than on mortality.