Prediction of systemic concentrations of sensitizing compound using TKTD simulation model.

To investigate the safe handling of an industrial product, phenyl vinyl sulfone (PVS), which has an extremely high potential for dermal sensitization at low concentrations and positive mutagenicity, the maximum no-effect concentration for dermal deposits was obtained from dermal sensitization experiments. The systemic concentrations in the liver, which is considered to be a target tissue of mutation, were monitored using the TKTD (Toxico Kinetics Toxico Dynamics) model by inputting the maximum no-effect concentration of sensitization. The predicted highest concentration in the liver was compared with the no-effect level of mutation in the same tissue, which was derived from an in vitro mutagenicity study.

alpha(2)-Macroglobulin: a novel cytochemical marker characterizing preneoplastic and neoplastic rat liver lesions negative for hitherto established cytochemical markers.

We tried to identify a novel marker characteristic for rat hepatocellular preneoplastic and neoplastic lesions, undetectable by well established cytochemical markers. Glutathione S-transferase placental (GST-P)-negative hepatocellular altered foci (HAF), hepatocellular adenoma (HCA), and hepatocellular carcinoma (HCC) were generated by two initiation-promotion models with N-nitrosodiethylamine (NDEN) and peroxisome proliferators, Wy-14,643 and clofibrate. Total RNAs isolated from laser-microdissected GST-P-negative HAF (amphophilic cell foci) and adjacent normal tissues were applied to microarray analysis.

Enhanced rat Hershberger assay appears reliable for detection of not only (anti-)androgenic chemicals but also thyroid hormone modulators.

Development of an internationally recognized standard for the Hershberger assay as a screening tool to detect potential (anti-)androgenic chemicals is in progress. In the present preliminary study, we evaluated the reliability of the enhanced Hershberger assay to detect thyroid hormone modulating activity, while concentrating attention on possible confounding influence on evaluation of (anti-)androgenic activity. Castrated or testosterone propionate (TP; 0.

Metabolism of diethofencarb (isopropyl 3,4-diethoxyphenylcarbamate) in rats: identification of metabolites in urine.

Rats were orally given a diethofencarb (isopropyl 3,4-diethoxyphenylcarbamate) labeled with (14)C, at 300 mg/kg/day, for 4 consecutive days, and 11 metabolites in urine were purified by a combination of several chromatographic techniques. The chemical structures of all isolated metabolites were identified by spectroanalyses (NMR and MS). Ten of them were newly identified forms.

Identification of a novel basic helix-loop-helix-PAS factor, NXF, reveals a Sim2 competitive, positive regulatory role in dendritic-cytoskeleton modulator drebrin gene expression.

Sim2, a basic helix-loop-helix (bHLH)-PAS transcriptional repressor, is thought to be involved in some symptoms of Down's syndrome. In the course of searching for hypothetical Sim2 relatives, we isolated another bHLH-PAS factor, NXF. NXF was a novel gene and was selectively expressed in neuronal tissues.

Lack of estrogenic or (anti-)androgenic effects of d-phenothrin in the uterotrophic and Hershberger assays.

Synthetic pyrethroids are among the most common insecticides and pesticides currently in use worldwide. Recently, d-phenothrin, a synthetic pyrethroid, is suspected to have endocrine activities through the estrogen and androgen receptors. However, no study has been conducted to evaluate its potential for hormonal activity using an in vivo test specifically focused on estrogenic and androgenic activities.

Development of the Simulation Model InPest for Prediction of the Indoor Behavior of Pesticides.

The objective was to develop a computer software package (to be registered as InPest) that runs under Microsoft Excel on a personal computer to help in the risk assessment of indoor-use pesticides for both applicators and indoor occupants for various methods of application including space spraying, electric vaporizing, broadcast spraying, and residual spraying. For space spraying, the movement of the pesticide in a sprayed room including droplet settlement, permeation into the floor, degradation, transference, and discharge by ventilation were described as precisely as possible by various physicochemi-cal equations. The equations thus obtained were then incorporated into the Fugacity model (Level IV).