This paper summarizes the results of toxicity studies of 2,3,3,3-tetrafluoroprop-1-ene（HFO-1234yf）, which has been developed as a refrigerant for the next generation, and the developmental 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, based on data published as openly available information. Only limited information on the toxicity of HFO-1234yf was available. HFO-1234yf did not show specific effects on acute, repeated exposure, cardiac sensitization and reproductive toxicity studies or particularly serious genotoxocity to living species. In developmental toxicity study of HFO-1234yf, pregnant rabbits died at 5,500 ppm and higher. In developmental toxicity studies of HFCs in rabbits, HFC-125 at 50,000 ppm, HFC-134a at 10,000 ppm and higher and HFC-32 at 50,000 ppm were maternally toxic, but not maternally lethal. Although this paper provides initial information on the toxicity of HFO-1234yf, further review of detailed information about the toxicity of HFO-1234yf is needed to adequately clarify its toxicity and assess the risks of this compound. Detailed information on toxicity studies of HFO-1234yf should be disclosed to ensure transparency concerning risk assessment of this compound.

View full abstract

This paper reviews studies on tissue distribution and toxicity after various routes of exposure to 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. Titanium（Ti）was detected in the lung and medistinal lymph nodes, but not in the liver, kidney, spleen or basal brain with olfactory bulb, in rats that inhaled nano TiO₂. Accumulation of TiO2 particles was observed in the brain, especially the olfactory bulb and hippocampus, after intranasal instillation of nano and fine TiO₂ in mice. After dermal application of ultrafine and fine TiO₂ in human volunteers, rabbits and pigs, deposition of Ti was observed in the stratum corneum and hair follicles, but not in the dermis. One report showed the accumulation of Ti in the spleen, heart, liver, lung and brain and histopathological changes in these tissues in mice that received dermal application of nano TiO₂. However, there are serious concerns about this report due to the housing conditions of animals, which might have negatively impacted the experimental results. After oral administration of nano and fine TiO₂ to mice, accumulation of Ti in the liver, kidney, spleen and kidney and histopathological changes in these organs and hippocampus were found. Although this review provides initial information on tissue distribution and toxicity after various routes of exposure to TiO2, further studies using characterized materials, relevant route of exposure, and dose closely reflecting actual levels of exposure are required.

View full abstract

Chronic toxicity of an antifouling biocide 4,5-dichloro-2-n-octyl-3（2H）-isothiazolone （Sea-Nine 211） for a marine teleostean fish, red sea bream （Pagrus major） was estimated from the acute to chronic ratio （ACR） obtained from the mummichog （Fundulus heteroclitus）. The mean 96-h median lethal concentration values of Sea-Nine 211 （based on the actual toxicant concentrations） for red sea bream and mummichog were 5.1 and 4.7 μg/L, respectively. Early life-stage toxicity （ELS） testing using mummichog embryos revealed that growth was the most susceptible endpoint, and the lowest and no-observed effect concentrations based on the actual toxicant concentrations were 2.8 and 1.1 μg/Lg/L, respectively. Thus, the maximum acceptable toxicant concentration was determined to be 1.8 μg/Lg/L. Using the calculated ACR value （4.7:1.8） for the mummichog, the chronic toxicity for red sea bream was predicted to be 2.0 μg/Lg/L. Considering the concentrations of Sea-Nine 211 currently detected in the coastal waters of Japan, we consider risk from using this biocide to the fish population to be low. In addition, Sea-Nine 211 exhibited acetylcholinesterase-inhibiting activity, but did not induce morphological abnormality in the ELS test. Accumulation of the toxicant in the body of mummichog may not be enough to cause morphological abnormality because of its rapid degradation.

View full abstract

The purpose of this study was to ascertain an availability of acute toxicity tests on marine phytoplankton, zooplankton and fish according to the guidelines for the toxicity tests on marine organisms described by the Fisheries Agency of Japan. The effect of Cr⁶⁺ in form of K₂Cr₂O₇ was analyzed. The 96h-EC₅₀ for Pavlova lutheri was 7.5 mg/L（95% confidencelimits 6.5-8.6 mg/L）and for Chaetoceros gracilis was 6.0 mg/L（95% confidence limits 5.1-7.1 mg/L）. The 24h-EC₅₀ for nauplii of Tigriopus japonicus was 42.5±5.5 mg/L. The 96h-LC₅₀ for Sillago japonica was 12.7±0.84 mg/L. As these effects values were at the same level as reported values, employed testing methods in this study were considered to be available for testing marine organisms. Required research work for the future was discussed and it was suggested that the data accumulation on acute and chronic effects would be essential for marine organisms for reliable estimation of PNEC（Predicted No-Effect Concentration）.

View full abstract

This paper introduces some test conditions, such as cultivation temperature, light intensity and medium, of the duckweed growth inhibition test using Lemna aoukikusa Beppu et Murata, L. aoukikusa Beppu et Murata subsp. hokurikuensis Beppu et Murata and L. aequinoctialis Welw. for test organism. These three species could be cultured under the same conditions of L. minor which is recommended in existing OECD test guideline （TG-221）. The relative sensitivity of six species of Lemna spp. to 3,5-dichlorophenol were determined. The sensitivity of these three species to 3,5-dichlorophenol was similar to L. minor or L. japonica.

View full abstract