Title
4-Week oral toxicity study of a combination of eight chemicals in rats: comparison with the toxicity of the individual compounds
Author
Centraal Instituut voor Voedingsonderzoek TNO
Jonker, D.
Woutersen, R.A.
van Bladeren, P.J.
Til, H.P.
Feron, V.J.
Publication year
1990
Abstract
In a 4-wk oral toxicity study, 4-wk-old male and female Wistar rats were exposed to a combination of arbitrarily chosen chemicals comprising sodium metabisulphite, Mirex, Loperamide, metaldehyde, di-n-octyltin dichloride, stannous chloride, lysinoalanine and potassium nitrite. The dose levels used were based on the 'no-observed-adverse-effect level' (NOAEL) and the 'minimum-observed-adverse-effect level' (MOAEL) of the individual compounds obtained in similar studies with Wistar rats previously performed at TNO-CIVO, and comprised 0 (controls), 1/10 and 1/3 of the NOAEL, the NOAEL and the MOAEL. In comparison with the adverse effects of the individual compounds, both more severe and less severe adverse effects were observed at the MOAEL of the combined compounds, indicating interaction of effects at this exposure level. Slightly decreased haemoglobin content and slightly increased relative kidney weight were the only treatment-related adverse effects seen in the NOAEL group. In the 1/10 and 1/3 NOAEL groups no untoward effects were found that could be related to treatment. The present study clearly demonstrates absence of a simple additive effect, and provides some, but no convincing, evidence for an increased risk from exposure to a combination of chemicals when each chemical is administered at its own individual NOAEL. At lower dose levels no increased risk appears to exist. These generalizations may not be fully justifiable from a purely scientific point of view but are the most important practical lesson learnt from the present study.
Subject
Dioctyltin dichloride
Hemoglobin
Loperamide
Lysinoalanine
Metaldehyde
Mirex
Potassium nitrite
Sodium metabisulfite
Stannous chloride
Unclassified drug
Animal experiment
Drug mixture
Kidney mass
Toxicity
Administration, oral
Body weight
Drug synergism
Drug toxicity
Organ weight
Pharmaceutical preparations
Animalia
Rattus norvegicus
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DOI
https://doi.org/10.1016/0278-6915(90)90170-r
TNO identifier
231290
Publisher
Elsevier, Amsterdam
ISSN
0278-6915
Source
Food and Chemical Toxicology, 28 (28), 623-631
Document type
article