The individual and combined metabolite profiles (metabolomics) of dibutylphthalate and di(2-ethylhexyl)phthalate following a 28-day dietary exposure in rats.

Metabolite profiles (metabolomics) of plasma samples of Wistar rats dosed with di(2-ethylhexyl)phthalate (DEHP - 3000ppm) and dibutylphthalate (DBP - 150, 1000 and 7000ppm) were individually determined in 28 days dietary studies. In addition, profiles of combined exposure to 3000ppm DEHP and either 150, 1000 or 7000ppm DBP were determined. High dose levels induced more profound metabolite changes in males than in females for both compounds. At 150ppm DBP (NOEL for toxicity) there were very few (

Effects of an ultraviolet B radiation absorber on photocarcinogenesis in hairless albino mice.

Uvinul T 150, a UVB absorber, was administered (concentration 5%) in a vehicle to the skin of hairless albino mice before ultraviolet radiation (UVR) exposure for 5 days per week in a photocarcinogenicity study. Uvinul T 150 prolonged the latency period to 50% skin tumor incidence (controls: 21-22 weeks; Uvinul T 150: 36 weeks in males and 31 weeks in females). When Uvinul T 150 was applied in an alternating-exposure procedure (3 days/week before and 2 days/week after UVR), the inhibition of photocarcinogenesis was less marked (latency period 28-30 weeks). The vehicle formulation had no effect (latency period 20-21 weeks). The sensitivity of the test system was demonstrated by a positive control (8-methoxy-psoralene). Although UVB absorption was shown to inhibit photocarcinogenesis, the results also suggest that UVA radiation makes a contribution to skin tumor formation.

Standardization of the perchlorate discharge assay for thyroid toxicity testing in rats.

The perchlorate discharge assay (PDA) is potentially of high diagnostic value to distinguish between direct and indirect thyroid toxicity mechanisms, provided that standard treatment times are established and positive controls yield reproducible results. Therefore the PDA was evaluated after 2 and/or 4 weeks of treatment with positive control compounds in rats. Phenobarbital, Aroclor 1254 and beta-naphthoflavone (indirect toxic mechanism) enhanced thyroidal radioiodide accumulation, and the administration of potassium perchlorate had no effect on thyroid: blood (125)I ratio. Phenobarbital caused follicular cell hypertrophy and hyperplasia in the thyroid and centrilobular hypertrophy in the liver, without effects on serum triiodotyronine (T(3)), thyroxine (T(4)) levels. Thyroid-stimulating hormone (TSH) levels were moderately increased. Propylthiouracil (direct toxic mechanism) caused severe thyroid follicular cell hypertrophy and hyperplasia, reduced serum T(3) and T(4) levels and increased serum TSH levels, and reduced thyroidal radioiodide accumulation; perchlorate administration significantly reduced thyroid: blood (125)I ratio, demonstrating an iodide organification block. Potassium iodide (direct toxic mechanism) virtually blocked thyroidal radioiodide accumulation, without significant effects on serum T(3), T(4), and TSH levels and a microscopic correlate for higher thyroid weights. Thus, positive controls yielded reproducible results and we conclude that both the 2- and 4-week PDA is suitable to distinguish between direct and indirect thyroid toxicity mechanisms.