Kikuo Yoshida

Cytotoxicity of 109 chemicals to goldfish GFS cells and relationships with 1-octanol/water partition coefficients

Abstract The midpoint cytotoxicity (NR50 values) of 109 chemicals including alcohols, aromatics, phenols and pesticides to goldfish scale GFS cells were compared with the fish acute toxicities and with the 1 - octanol/water partition coefficient (Pow). The NR50 values were significantly correlated to the available acute toxicity data for fathead minnow (n=31, r=0.958, s=0.480, F=325) and guppy (n=29, r=0.957, s=0.482, F=294). The Pow gave a good correlation in simple linear regression analysis for all compounds excluding 8 compounds that the NR50 values could not be obtained for their low solubility in culture medium. Log 1 NR 50 (mM) = (0.87±0.08) Log Pow − (2.17±0.24) ( n =101, r =0.914, s =0.587, F =505) For 29 narcotic type of compounds, the regression analysis revealed a high correlation between the NR50 values and Pow, and appeared to give a baseline cytotoxicity. Log 1 NR 50 (mM) = (0.77±0.06) Log Pow − (2.48±0.12) ( n =29, r =0.984, s =0.252, F =817) And also, the regression analyses between NR50 and Pow for some types of compounds were discussed. These results suggest that NR assay is useful for prediction of acute toxicity to fish and studies of quantitative structure-activity relationships (QSARs).

A GIS-based evaluation of the effect of decontamination on effective doses due to long-term external exposures in Fukushima.

Despite the enormous cost of radiation decontamination, there has been almost no quantitative discussion on how much it would reduce the long-term external radiation exposure in the Evacuation Zone and Planned Evacuation Zone (restricted zone) in Fukushima. The aim of this study is to assess the effectiveness of decontamination and return options and to identify important parameters for estimating the long-term cumulated effective dose (CED) during 15, 30 and 70 year period using data on land-use, population and decontamination in the restricted zone (about 1100 km(2)) in Fukushima. Decontamination of the land is assumed to have a certain efficacy in terms of the reduction of CED. The EeCC (external exposure conversion coefficient) is the parameter having the greatest effect on the percentage of area having CED during the 30 years above 100 m Sv after decontamination, ranging from 13% (EeCC=0.2) to 55% (EeCC=0.6). Therefore, we recommend a detailed investigation of the EeCC in Japan.

Validation of modeling approach to evaluate congener-specific concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans in air and soil near a solid waste incinerator.

A concise modeling approach using long-term averaged meteorological data was developed to estimate site-specific concentrations of congeners of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) near a solid waste incinerator. This approach consists of calculation of atmospheric dispersion, dry and wet deposition of gaseous and particle-bound congeners, and non-steady-state concentrations in soil. The predictability of this approach was evaluated by comparison of calculated concentrations of congeners in soil with those measured at eight locations near a municipal solid waste incinerator (MSWI). The variation of these concentrations due to variability of meteorological parameters is small. A considerable number of mean values show good agreement with measured concentrations within a factor of three. The reasonable agreement between calculated and measured concentrations indicates that algorithms for the calculation of vapor-phase deposition and non-steady-state concentrations in soil must be included in the modeling approach for an accurate estimation of the concentrations of congeners of PCDD/Fs emitted from MSWIs to the atmosphere. For a detailed estimation of site-specific concentrations, it is important to specify the bulk density of soil in the evaluated area, together with meteorological parameters.

Reproductive and developmental toxicity of degradation products of refrigerants in experimental animals.

The present paper summarizes the results of animal studies on the reproductive and developmental toxicity of the degradation products of refrigerants, including trifluoroacetic acid (TFA), carbon dioxide (CO(2)), carbon monoxide (CO), carbonyl fluoride (CF), hydrogen fluoride (HF) and formic acid (FA). Excessive CO(2) in the atmosphere is testicular and reproductive toxic, embryolethal, developmentally neurotoxic and teratogenic in experimental animals. As for CO, maternal exposure causes prenatal and postnatal lethality and growth retardation, skeletal variations, cardiomegaly, blood biochemical, immunological and postnatal behavioral changes, and neurological impairment in offspring of several species. Very early studies of CO in rats and guinea pigs reported fetal malformations in exposed dams. The results of toxicological studies on sodium fluoride (NaF) were used to obtain insight into the toxicity of CF and HF, because CF is rapidly hydrolyzed in contact with water yielding CO(2) and HF, and NaF is similar in kinetics and dynamics to HF. Increased fetal skeletal variation, but not malformation, was noted after the maternal administration of NaF. Rat multiple-generation studies revealed that NaF caused retarded ossification and degenerative changes in the lung and kidney in offspring. There is a lack of information about the toxicity of TFA and FA.

Reproductive and developmental toxicity of hydrofluorocarbons used as refrigerants.

The present paper summarizes data on the reproductive and developmental toxicity of hydrofluorocarbons (HFCs), including 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. No developmental toxicity of HFC-125 was found even at 50,000 ppm in rats or rabbits. Although HFC-134a exhibited no dominant lethal effect or reproductive toxicity in rats, it caused low body weight in pre- and postnatal offspring and slightly retarded skeletal ossification in fetuses at 50,000 ppm in rats. No maternal or developmental toxicity was noted after exposure to HFC-143a even at 40,000 ppm in rats or rabbits or HFC-152a even at 50,000 ppm in rats. HFC-32 is slightly maternally and developmentally toxic at 50,000 ppm in rats, but not in rabbits. HFC-245fa caused decreases in maternal body weight and food consumption at 10,000 and 50,000 ppm and fetal weight at 50 000ppm. No evidence of teratogenicity for these HFCs was noted in rats or rabbits. There is limited information about the reproductive toxicity of these HFCs. Animal studies remain necessary for risk assessments of chemicals because it is difficult to find alternative methods to determine the toxic effects of chemicals. It is required to reduce emissions of organic vapors containing HFCs to reduce the risk of exposure.

Estimation of dioxin risk to Japanese from the past to the future.

The transport processes of seventeen 2,3,7,8-chlorinated congeners of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) from their major sources to humans were modeled to estimate the time course, from the past to the future, of the human health risk to the Japanese population. The comparison between measured and estimated values showed that the present modeling approach represented the background levels of congeners in the environment, daily intake, and body burden reasonably well, except for in the case of 2,3,7,8-TCDF. Although PCDD/Fs in herbicides have contributed greatly to the daily intake and body burden to the Japanese population in the past, the main sources of the present intake and burden of PCDD/Fs is estimated to be incinerators. The margin of exposure (MOE) for the risk of morphological reproductive alteration in female offspring exposed prenatally was calculated based on the estimated maternal body burden. The results indicated that the MOE values were in the single digits, implying that these values may not be sufficiently large to guarantee the safety of female offspring of mothers born in the 1950s, whereas the MOE values for female offspring born in and after the latter half of the 1990s may be sufficiently large to guarantee safety.

Dioxin health risk to infants using simulated tissue concentrations

Dioxin concentrations in infant and child were simulated using physiologically based pharmacokinetic (PBPK) models developed for these groups. The infant model was validated by comparing the simulated concentration with the measured concentration from the literature, and they showed good agreement. Simulations with our PBPK model showed temporal patterns in concentrations in various tissues. For risk assessment, estimated concentrations of 29 dioxins in the liver were summed up in a toxic equivalency (TEQ) basis to be compared with actual 2,3,7,8-TCDD concentrations in rat liver associated with toxicity. Maximum liver concentrations in breast-fed and formula-fed infants were 16.8pg TEQ/g and 3.5pg TEQ/g, respectively. The level in breast-fed infant liver was approximately 1/300 of the level associated with hepatocellular carcinoma and 1/5 of the level found in maternal rat liver associated with alterations in reproductive organs in the next generation. Based on our analysis, the present contamination level is not safe enough, but further dose-response data is required for a quantitative risk assessment.

Practical Approaches Proposed for Population-level Risk Assessment of Chemicals: A Case Study of 4-nonylphenol Using Life-cycle Toxicity Data for Medaka (Oryzias latipes)

The ecological risk for chemicals should be evaluated from the viewpoint of population-level impact. To date, however, there are still no practical approaches to the assessment of the population-level impact of chemicals in order to develop appropriate plans for chemical management. In an attempt to address this urgent issue, we firstly proposed two population-level approaches based on state-of-the-art approaches to population-level risk assessment. Thereafter, as a case study, we applied the two approaches to the quantitative assessment of the potential impact of 4-nonylphenol (4-NP) on medaka (Oryzias latipes) in terms of reduction of population growth rate (λ). An age-classified projection matrix (daily time-step) model was developed and used as a tool for incorporating life-cycle survivorship and fecundity data obtained for individual-level responses of medaka exposed to 4-NP into population-level responses such as λ. Based on the resulting λs, the two proposed population-level approaches were then examined. The predicted no-effect concentration (PNEC) for population-level impact based on the threshold concentration (defined as the concentration at λ=1), as well as the lowest-observed-effect concentration (LOEC), the non-observed-effect concentration (NOEC), and the maximum-acceptable-toxic concentration (MATC) were then derived. The results suggest values for PNEC ranging between 0.82 and 2.10μg·l-1 for medaka population growth impact under 4-NP exposure. Although these two approaches still have limitations, current knowledge indicates that they are reasonable and practical approaches to the evaluation of population-level impact.