Warfarin is commonly used worldwide as a rodenticide. Warfarin inhibits blood coagulation, and continuous intake of warfarin causes potentially fatal hemorrhages. However, warfarin-resistant roof rats（Rattus rattus）are found in Japan, especially in the Tokyo area. Recently, warfarin-resistant brown rats（Rattus norvegicus）were discovered in rural areas of Japan. Warfarin-resistant house mice have not been reported, but it is highly possible that resistant mice will be also found in our country. Warfarin-resistant rats, which have acquired resistance to anticoagulant rodenticides, are called &ｌquot;super rats&ｒquot;. Rodenticide-resistant roof rats, brown rats, and house mice have been also reported in the United States and European countries, e.g., Britain, France, Denmark, and Germany. In addition, warfarin-resistant rodents may be widespread in other countries that have not been investigated yet. The warfarin target molecule is vitamin K epoxide reductase（VKOR）．Warfarin inhibits the function of VKOR, which recycles vitamin K to activate blood coagulant factors, and causes hemorrhage. Substitutions in the VKORC1 gene were reported in warfarin-resistant rodents. Moreover, the metabolism of warfarin is accelerated in warfarin-resistant rats due to the elevation of cytochrome P450-dependent xenobiotic metabolizing activities. The combination of a VKOR mutation and P450 acceleration causes warfarin resistance in wild rodents, which is an evolutionary adaptation to the pesticide-polluted environment. After the appearance of warfarin-resistant rodents, a second-generation rodenticide was developed and replaced warfarin in Europe and America. In Japan, difethialone is the only the second-generation rodenticide that can be used in public buildings. In Japan, a critical zoonosis infection has not yet spread on a large scale through wild rodents. However, it is necessary to consider how to prevent serious infestation by house rodents in the industrial, administrative, and academic sectors before such infestation occurs.

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The present paper summarizes the genotoxicity of titanium dioxide（TiO₂），widely used in the production of paints paper and plastics, as food additives and colorants, and increasingly, as nanpoparticles in pharmaceutical and cosmetics products, based on data published in openly available scientific literature. Many studies have examined the genotoxicity of TiO₂ nanoparticles, using in vitro comet assays, bacterial and mammalian cell mutation tests, chromosomal aberration assays and micronucleus assays, and in vivo and ex vivo assays. Positive results were observed in tests on DNA damage, mammalian cell mutation, mammalian cell chromosome aberration, sister chromatid exchange, conventional and cytokinesis-blocked micronuclei frequency, and hprt mutation frequency. Some studies suggest that the genotoxicity of TiO₂ nanoparticles results from oxidative DNA damage. Results of studies in vivo correlated with results obtained in vitro are helpful for interpretation of the data. Genotoxicity studies with negative outcomes are also reported. A battery of standard genotoxicity testing methods covering a wide range of mechanisms is adequate to clarify the genotoxicity of TiO₂ particles.

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The present paper summarizes data on the toxicity of hydrofluorocarbons（HFCs）， including 1,1,1,2,2-pentafluoroethane（HFC-125），1,1,1,2-tetrafluoroethane（HFC-134a）， 1,1,1-trifluoroethane（HFC-143a），1,1-difluoroethane（HFC-152a），difluoromethane （HFC-32），and 1,1,1,3,3-pentafluoropropane（HFC-245fa），used as refrigerants, published in openly available scientific literature. Acute exposure to HFC-152a, but not other HFCs, caused deaths in rats at 383,000 ppm. These HFCs, except for HFC-32, caused a cardiac sensitization in dogs at high concentrations. Although myocarditis was found after repeated exposure to HFC-245fa for 13 weeks at 10,000 ppm and above, no overt toxicity was noted after repeated exposure to other HFCs. HFC-134a, HFC-32, and HFC-245fa caused developmental toxicity at 50, 000 ppm, but these HFCs were not teratogenic. Toxic effects of HFC-134a are relatively well reported, but limited information is available regarding the toxicity of other HFCs. Animal studies are necessary for risk assessments of chemicals because it is difficult to find alternative methods to determine the toxic effects of chemicals. It is important to reduce emissions of organic vapors containing HFCs to reduce the risk of exposure and protect public health.

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The program for presenting quantitative structure-activity relationship(QSAR)was developed and named PAS(Platform for Assessment from Structure)．The display process of a chemical structure and input system of SMILES notation through the chemical structure are essential in QSAR presentation. In Part 2, the programming art for presentation of a chemical structure employed in PAS is discussed. In PAS, fused rings are collocated by simple ring crossing method and the groups of the rings are connected by adjusting the angle and position of the binding bond. The non-cyclic part is drawn just as a branch grows up from a trunk.

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The PAS(Platform for Assessment from Structure) has a characteristic method in getting the partial structures. The structural specifications to be extracted are described as a text according to the defined syntax and the program interprets the terms. The syntax employed is named as FITS(Fragment Identification by Tree System)．The program succeeded in getting the same number of 103087 chemicals for 362 fragments and 381 factors used in the logP value calculation by EPI-SUITE. In Part 3, the FITS system is discussed.

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Two marine fishes, Japanese sea bass and red sea bream, were exposed to dietary tributyl tin（TBT）for two weeks to examine its immunotoxicity in relation to their body burdens. TBT body burdens of test fishes were also compared to TBT body burdens of their wild and cultured counterparts to predict their immune function inhibition.
TBT concentrations of both fishes were significantly increased when dietary TBT concentrations were increased. While one of the non-specific immune responses, phagocytosis by neutrophil was not inhibited by TBT, another response, NBT reduction as a measure of oxidative burst of both fish species was inhibited even in the lowest dietary TBT concentration. Reverse sigmoid curve relationships were observed between inhibition of oxidative burst and TBT body burden in both fish species. TBT concentrations of some wild sea bass and cultured red sea bream were higher than the observed TBT concentrations of the lowest concentration exposure group of the present study.
These results suggest that non-specific immune response of wild sea bass and cultured red sea bream can be inhibited by TBT contamination.

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We performed acute toxicity tests using 2-chloroacetamide（a fungicide）on Eisenia fetida to compare susceptibility among various-sized earthworms. A controlled method of rearing Eisenia fetida was developed to provide individuals of the desired sizes. Eisenia fetida was cultured in an artificial soil using a mixture of dried rolled barley and spinach （4:1）powder as food in a controlled room（20［or 22］±1°C; 18［or 16］-h light: 6［or8］-h dark）．Cocoons（four hundreds, usually）collected from the artificial soil were introduced into rearing water（dechlorinated tap water），and hatched juveniles were cultured in the artificial soil to the desired weight. Our findings indicate that small individuals（30～100 mg wet wt.）may be used for the acute toxicity test instead of adult earthworm（OECD test guideline <: 300 mg）to diminish the amount of contaminated soils and space （continuous light）required for the toxicity test. Other test conditions such as continuous light during the test（TG-204），testing chemicals in water instead of the filter paper contact rest（TG-204），and suitability of 2-chloroacetoamide as a reference substance were also investigated to improve the efficiency of the earthworm toxicity test.

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