Yoko Katakura

Visual dysfunction in workers exposed to a mixture of organic solvents.

The aim of this study was to investigate the relationship between the workers occupationally exposed to a mixture of organic solvents and their visual functions. Here the visual functions included color vision (CV), visual contrast sensitivity (CS) and visual evoked potentials (VEP). Test subjects were 182 workers at 53 furniture factories in the same industrial area of Japan. As control, a group consisted of 96 workers without exposure to any organic solvent was also tested. Exposure assessments were made both by the environmental concentration and biological monitoring. CV and CS tests were carried out for all the subjects. VEP was measured for 21 exposed subjects who were considered to have impaired CV and CS. In the results, the color confusion index (CCI) values of the exposed subjects were significantly higher than that of the age-matched controls (P<0.01). Their CS values were significantly lower than those in the controls at spatial frequencies of 6 and 12 cycles per degree (cpd) (P<0.01 and <0.05, respectively). A significant correlation between the concentration of urinary methylhippuric acid and contrast sensitivity was found by a multiple regression analysis (P<0.05). CCI showed a negative correlation at all spatial frequencies of CS in a simple regression analysis, no abnormal data were found by the VEP test in the exposed subjects who were found to have impaired CV and CS. The results suppose that a low concentration of the mixed organic solvents might affect the retina and optic nerve. However, it needs to be further researched if such an impact affects the Brodmanns areas of visual cortex in the brain.

Relation between colour vision loss and occupational styrene exposure level.

Aims: To investigate the relation between colour vision loss and the exposure level of styrene. Exposure level included the current exposure concentration, past cumulative exposure, and the maximum exposure level in the past. Methods: Colour vision was examined by the Lanthony desaturated panel D-15 test for 76 subjects exposed to styrene in a fibreglass reinforced plastics boat plant (as an exposed group) and 102 non-exposed subjects (as a control group). The current exposure level was expressed by the concentration of atmospheric styrene and end shift urinary mandelic acid (MA) and phenylglyoxylic acid (PGA) levels. The individual cumulative exposure index (CEI) was calculated, based on the exposure frequency and urinary MA concentrations measured for the past eight years. Results: The Colour Confusion Index (CCI) of the exposed group showed a significant difference from the age matched controls. However, only a slight significant relation was found between CCI and the concentration of urinary MA plus PGA. In this study, the exposed group was further divided into two subgroups (as sub-MA+PGA groups) by the median of urinary MA plus PGA of each subject. The dividing line between the subgroups was 0.24 g/g creatinine, which was equivalent to an atmospheric concentration of styrene of about 10 ppm. The CCI values of both the sub-MA+PGA groups were significantly higher than that of the control group. The relation between CCI value and the maximum exposure concentration in the past eight years was examined. It was found that the CCI values of the group with the maximum exposure concentration of styrene over 50 ppm were significantly higher than that of the other groups. Conclusions: Exposure to styrene would impair colour vision even if the exposure concentration was lower than 10 ppm. Furthermore, if the maximum concentration of styrene exposure transiently exceeded 50 ppm in the past, the styrene related damage might remain. Thus, the safe limit of exposure to styrene and the relation between exposure to styrene and the degree of damage to ocular structure, retina, optic nerve, and brain need to be re-examined.

Risk factors for human alveolar echinococcosis: a case-control study in Hokkaido, Japan

A case-control study to determine the risk factors for human alveolar echinococcosis (AE) was conducted in Hokkaido, Japan. The 134 cases were either patients clinically diagnosed as having AE (N =61) or other individuals found to be seropositive for Echinococcus multilocularis although showing no abnormalities in ultrasound scans (N = 73). Two groups of case-matched controls were employed: one of 670 individuals selected from a list of residents of Hokkaido (group A) and the other of 650 subjects selected from a list of individuals who had been found seronegative in earlier investigations (group B). Because of the long latency of AE, potential risk factors were studied over two different periods: for the 0-10 and 11-20 years before the year of diagnosis/recorded seropositivity. The results of multivariate analyses, in which the cases were compared with each control group, indicated that the rearing of cattle and pigs and the use of well water were significant risk factors and that the use of tap water significantly decreased the risk of an individual having AE. Extension of the piped water supply and health education on improving the disposal of household rubbish (to keep foxes away from houses) should help reduce the risk of AE infection in the study area.

Effects of Pregnancy, Age and Sex in the Metabolism of Styrene in Rat Liver in Relation to the Regulation of Cytochrome P450 Enzymes

Effects of Pregnancy, Age and Sex in the Metabolism of Styrene in Rat Liver in Relation to the Regulation of Cytochrome P450 Enzymes: Reiko Kishi, et al. Department of Public Health, Hokkaido University Graduate School of Medicine—To elucidate the effect of maternal styrene exposure, which is due to various postnatal changes in the development and behavior of offspring, we investigated pregnancy‐induced changes in the metabolism of styrene in rat liver in relation to the regulation of cytochrome P450 enzymes. We also examined age and sex‐induced changes in the metabolism of styrene. Pregnancy appeared to exert a negative effect on cytochrome P450 content at the late stage, whereas microsomal protein content showed little change during pregnancy. Pregnancy significantly decreased the rate of formation of styrene glycol at the late stage. The percentage of remaining activity in microsomes exposed to anti‐CYP2E1 was lower than that exposed to anti‐CYP2C11/6 in pregnant and non‐pregnant female rats and immature male rats, indicating that CYP2E1 contributes to the metabolism of styrene more than CYP2C11/6 in these rats. Although pregnancy seemed to decrease styrene metabolism, the contribution of CYP2E1 seemed to be slightly increasing. In conclusion, pregnancy clearly influences the metabolism of styrene as well as other characteristic factors such as age and sex. It is very important to elucidate the changes in specific P450 isozyme composition related to their characteristic modification and in their affinity for chemicals.

Acute effects of trichloroethylene on blood concentrations and performance decrements in rats and their relevance to humans.

This study was designed to clarify the nature of effects of trichloroethylene (TCE) on the central nervous system, and to determine the critical concentrations in blood associated with specific behavioural changes. This was achieved by a follow up of the whole time course of TCE intoxication during and after exposure. The effects of a single four hour exposure to TCE on signalled bar press shock avoidance in rats were tested by methods previously applied to investigate the acute neurobehavioural effects of exposure to toluene. Even low exposure to TCE induced shock avoidance performance decrements in rats. Rats exposed to 250 ppm TCE showed a significant decrease both in the total number of lever presses and in avoidance responses at 140 minutes of exposure compared with controls. The rats did not recover their pre-exposure performance until 140 minutes after the exhaustion of TCE vapour. Exposures in the range 250 ppm to 2000 ppm TCE for four hours produced concentration related decreases in the avoidance response rate. No apparent acceleration of the reaction time was seen during exposure to 1000 or 2000 ppm TCE. The latency to a light signal was somewhat prolonged during the exposure to 2000 to 4000 ppm TCE. It is estimated that there was depression of the central nervous system with slight performance decrements and the corresponding blood concentration was 40 micrograms/ml during exposure. Depression of the central nervous system with anaesthetic performance decrements was produced by a blood TCE concentration of about 100 micrograms/ml. These results showed effects of TCE on the central nervous system that were considered to be a function of both the exposure concentration and the duration of exposure, which are closely related to the TCE concentration in blood.

Placental transfer and tissue distribution of 14C-styrene: an autoradiographic study in mice

The distribution of 14C-styrene was studied in the pregnant mouse using a whole body low temperature autoradiographic technique. In unsectioned tissues studied by liquid scintillation the concentrations of styrene and its metabolites in maternal and fetal blood and organs and in the placenta and amniotic fluid were determined. The organs which had higher concentrations of volatile styrene were maternal lung, kidney, liver, adipose tissue, and brain in mice killed shortly after injection. Non-volatile metabolites were localised in the lung, liver, kidney, gall bladder, and intestine. There were considerable amounts of radioactivity in the fetuses, though the concentrations were not as high in the maternal tissues. Fetal tissue levels were almost the same as maternal brain in mice killed from one to six hours after injection. The concentrations of styrene and its metabolites in placenta and amniotic fluid were about twice those in the fetal tissues. The placenta seems to play the part of a barrier for the fetus.

Effects of prenatal exposure to styrene on neurochemical levels in rat brain

Styrene was evaluated to determine its neurochemical effects in the offspring of rats exposed during the gestation period. Maternal Wistar rats were exposed to 0, 50 or 300 ppm styrene during gestation days 6 to 20 and the neurochemical effects on their offspring were compared with their pair-feeding and ad lib. feeding controls. The cerebrum weights at birth on day 0 were significantly lower than those for an ad lib. feeding control group. Neurotransmitter analyses showed decreases of neuroamines, especially 5-hydroxytryptamine and homovanillic acid in the cerebrum of newborn offspring of dams receiving a 300 ppm styrene exposure compared with the ad lib. fed control group and homovanillic acid was also decreased compared to the pair-feeding control. On postnatal day 21, the styrene-exposure pups showed a significant decrease of 5-hydroxyindoleacetic acid in the frontal neocortex compared with the ad lib. control group. In the hippocampus a significant decrease of 5-hydroxyindoleacetic acid was observed compared with both control groups. Moreover, the ratio of 5-HIAA/5-HT in the hippocampus was significantly decreased among the styrene-exposure groups. The 50 ppm styrene exposed group induced increase of concentrations of 5-hydroxytryptamine in the striatum. These results suggest that prenatal styrene exposure affects the developing fetal brain in terms of a few signs of neurochemical alteration.

Effects of styrene exposure on vibration perception threshold.

OBJECTIVES We aimed to investigate whether styrene can affect the vibration perception threshold (VPT) and to examine the dose-effect relationship at current and past styrene exposure levels. METHODS VPT was examined using a Vibrometer (TM-31A) for 67 subjects exposed to styrene in a fiberglass reinforced plastic boat plant and 151 non-exposed subjects. We selected 67 age-matched controls out of the non-exposed subjects for the analyses. End shift urinary metabolites of styrene were measured for evaluation of the dose-effect relationship for the past eight years and at the time of VPT measurement. The current exposure level was expressed by the end shift urinary mandelic acid (MA) and phenylglyoxylic acid (PGA) levels. Cumulative exposure index (CEI) were calculated based on the exposure frequency and urinary MA concentrations measured for the past eight years. RESULTS The VPT of the exposed group was higher than that of non-exposed group. Multiple regression analysis revealed that past maximum exposure level and age were significant factors explaining the variation of VPT. Dose-effect relationship was recognized in upper limbs but not in lower limbs among exposure groups. When the exposed group was divided into high- and low-level groups for the past maximum exposure level by the cutoff point of MA 0.83 g/g cr (equivalent to 50 ppm in air) and compared to the control group, we found significant differences in the VPT in upper limbs, between the high-level exposed group and control group, and in lower limbs, between both of the high- and low-level exposed groups and the control group. CONCLUSION If the maximum concentration of styrene exposure exceeded 50ppm in the past, effects of exposure to styrene on the VPT are likely to persist.