Toxicology of Industrial Compounds

320 ANTIOXIDANTS AND LIGHT STABILISERS: TOXIC EFFECT
Table 23.2 Parent equivalents and blood metabolites of [ 14 C]-labelled Compound B
after single oral administration of 9.5 mg kg −1 body weight to male rats
Note:
bld: below the limit of detection.
Blood was taken at the indicated time intervals and extracted with ethyl acetate for
analysis. Compound B and its free carboxylic acid metabolite (Compound A,
Table 23.1) were identified by thin-layer co-chromatography with authentic
reference samples. Quantification of Compounds A and B was accomplished by
radiometric scanning of the plates following thin-layer chromatography of the
respective blood extracts.
1000 ppm, liver weights as well as the investigated biochemical parameters
returned to control levels. Therefore, Compound B may be addressed as a
reversible barbiturate- and peroxisome proliferator-type inducer in the rat,
as characterised by its liver enzyme induction profile.
Effects on serum thyrotropin and thyroid hormones
When male rats were fed Compound B admixed in the diet for 14 days at
dose levels of 50, 150, 500 and 1000 ppm, liver and thyroid weights were
increased in a dose-dependent manner. Histopathological examination of
the thyroid gland revealed hypertrophy of the follicular epithelium and
thinning of colloid at 150, 500 and 1000 ppm. Morphological changes in
the pituitary gland comprised enlarged thyrotropin (TSH)-producing cells
with foamy or vacuolated cytoplasm. In addition, treatment resulted in
markedly increased serum TSH and reverse triiodothyronine (rT 3)
concentrations, whereas serum thyroxine (T 4) and triiodothyronine (T 3)
levels were found slightly decreased. The effects observed at 1000 ppm
were found to be reversible after a 28-day recovery period (Muakkassah-
Kelly et al., 1991).
In additional experiments, male rats were rendered hypothyroid, fed
Compound B at 1000 ppm for 21 days and infused for the last 7 days with
slightly supraphysiological concentrations of T 4. The observed changes in