Development of a category approach to predict the testicular toxicity of chemical substances structurally related to ethylene glycol methyl ether.

We propose a category approach to assessing the testicular toxicity of chemicals with a similar structure to ethylene glycol methyl ether (EGME). Based on toxicity information for EGME and related chemicals and accompanied by adverse outcome pathway information on the testicular toxicity of EGME, this category was defined as chemicals that are metabolized to methoxy- or ethoxyacetic acid, a substance responsible for testicular toxicity. A Japanese chemical inventory was screened using the Hazard Evaluation Support System, which we have developed to support a category approach for predicting the repeated-dose toxicity of chemical substances.

A category approach to predicting the repeated-dose hepatotoxicity of allyl esters.

We tested a category approach to predict the hepatotoxic effects of repeated doses of allyl esters using a new database for repeated-dose toxicity. Based on information on hepatotoxic mechanism of allyl acetate, the category was defined as allyl esters that are hydrolyzed to allyl alcohol. Allyl alcohol is readily oxidized to acrolein in the liver, causing hepatotoxicity.

A category approach to predicting the hemolytic effects of ethylene glycol alkyl ethers in repeated-dose toxicity.

Categorizing chemicals is an approach with the potential to reduce animal testing for hazard assessment of chemicals. In this study we investigated the category approach for testing the hemolytic effects of ethylene glycol alkyl ethers (EGAEs) for repeated-dose toxicity (RDT). Using mechanistic information on the hemolytic effects of ethylene glycol butyl ether, a toxicologically meaningful category was built on the basis of similarity of metabolism, mode of action and the hemolytic effects of several EGAEs and related chemicals.

Cholinergic and dopaminergic mechanisms involved in the recovery of circadian anticipation by aniracetam in aged rats.

We have reported that repeated administration of aniracetam (100 mg/kg p.o.) for 7 consecutive days recovers mealtime-associated circadian anticipatory behavior diminished in aged rats.