Environmental Engineering Reference
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frequency and duration of exposure; appropriateness of the species, strain, sex
and age of the animals used; the numbers of animals used per dosage group; jus-
tification of dose, route and frequency of dosing; and the conditions under which
the contaminant was tested.
There are many guidelines to the generation of scientifically valid data which
concern good experimental design, laboratory practice and reporting, e.g., OECD
and US EPA guidelines, and accepted codes of Good Laboratory Practice (OECD
1982 ;USEPA 1983 ).
The competency and completeness of the conduct and reporting of the study.
The effects of modifying factors that may result in major inequalities between
control and test animals.
This qualitative consideration has more to do with the evaluation and interpre-
tation of data than with acceptability of documentation. It is placed here because
determination of the factors which may have a major influence on toxicological data
needs to be made prior to the analysis of the data. There are many factors influencing
the responses of experimental animals to experimental treatment; some of these are
discussed by Doull ( 1980 ). Some influences may be quite subtle, as exemplified by
studies performed by Thompson et al. ( 1982 ), in which it was noted that the onset
of acute pulmonary oedema in rats being used in immune hypersensitivity studies
was sudden and seasonal. Circadian rhythms and seasonal physiological variations
can subtly influence experimental results. Such factors influencing animal responses
can be troublesome when their effects are confused with or misinterpreted as toxic
responses to treatment
The acceptability of reports and other technical information is primarily a sci-
entific judgment. Therefore, the rationale for rejecting a Hazard Assessment study
should be succinctly stated in the evaluation document.
12.3.4 Analysis and Evaluation of Toxicity Studies
Useful guidance documents for evaluating data and conducting assessments include
the IPCS Environmental Health Criteria (EHC) monographs specifically EHC 6, 70,
104 and 141 (WHO 1978 , 1987 , 1990 , 1992 ).
12.3.5 Analysis and Evaluation of Major Study Parameters
Concurrent control groups should always be used; notwithstanding the value of
historical control ranges in tumorigenicity studies. It is generally not appropriate
to rely on statistical comparisons with historical controls since the incidence of
spontaneous lesions can vary significantly over time (and even between concurrent
randomised control groups). Controls must be age-matched because some forms
of toxicity represent no more than acceleration and/or enhancement of age-related
changes.
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