Results of recognition tests on Japanese subjects of the labels presently used in Japan and the UN-GHS labels.

The UN-GHS, a globally harmonized system of classifying and labeling chemicals that was recommended by the United Nations in 2003, will be implemented globally in 2008. This system is expected to encourage people to behave in a way that reduces the risk of accidents or diseases caused by chemicals. However, the UN-GHS differs significantly from the present Japanese system of classifying and labeling chemicals. In particular, since the Japanese system does not require pictographic labels, ordinary Japanese people are not familiar with the new pictographic labels defined in the UN-GHS. Hence, before introducing the UN-GHS at the Japanese workplace, it is critical to clarify the actual usage conditions and the problems that this labeling system of hazardous chemicals poses, and to manage the related problems. We conducted recognition tests on Japanese subjects of the labels presently used in Japan and the UN-GHS labels. The results revealed that the subjects faced some difficulty in recognizing the meanings of some UN-GHS labels. The percentage of questions that were answered correctly with regard to the labels depicting 'cylinder,' 'corrosion,' 'health hazard,' and 'aqueous hazard,' with no accompanying explanatory statements, was less than 60. The results of the answers regarding the labels depicting 'flame' and 'flame over circle' revealed that many subjects were unable to distinguish one from the other. Further, many subjects were unable to clearly distinguish 'skull and crossbones' from 'health hazard.' These results indicate that it is very important to impart correct education regarding these labels.

Estrous cyclicity and ovarian follicles in female rats after prenatal exposure to 3,3',4,4',5-pentachlorobiphenyl.

Alterations of estrous cyclicity and ovarian follicles following prenatal exposure to PCB126 were examined. Female SD rats were given (i.g.) 25 pg, 2.5, 250 ng and 7.5 microg of PCB126/kg or the vehicle on days 13-19 postconception. Vaginal opening (VO) in the 250 ng and 7.5 microg offspring was significantly delayed. All groups showed irregular estrous cyclicity following VO, but it became normal after a few days. However, the start of normal estrous cyclicity following VO in the 2.5, 250 ng and 7.5 microg groups was significantly delayed. At 30 and 50 days old, the 2.5, 250 ng and 7.5 microg groups showed significantly fewer antral follicles and a higher number of atretic follicles. The 7.5 microg group at 50 days old revealed significantly fewer corpus luteums. In 50-day-old offspring, the 2.5, 250 ng and 7.5 microg groups showed a significant reduction in serum 17beta-estradiol and progesterone levels and significantly higher levels of PCB126 in the fatty tissue compared with the vehicle group. Thus, while the prenatal dose of PCB126 used in this study did not induce malformation of the external genitalia or persistent ovarian disruption, disruption of ovarian function at puberty was found in the 2.5 ng group of pups born to dams exposed to 17.5 ng/kg PCB126. The present study suggests that PCB126, at least in part, exerted direct effects on the ovary as shown by the disruption of estrous cyclicity.

Mammary gland differentiation in female rats after prenatal exposure to 3,3',4,4',5-pentachlorobiphenyl.

Recently we reported finding that prenatal exposure to a relatively low dose of 3,3',4,4',5-pentachlorobiphenyl (PCB126) increases the rate of 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary carcinoma, while a high dose decreases it. One of the most important factors determining sensitivity of the mammary gland to neoplastic stimuli is its stage of differentiation at the time of exposure to the carcinogenic agent. Hence, to verify a biphasic dose-response relationship (enhancement of carcinogenesis at low dose, and inhibition at high dose), we investigated the effects of prenatal exposure to PCB126 on mammary gland differentiation. Female SD rats were injected (i.g.) with 25 pg, 2.5 ng, 250 ng, 7.5 microg of PCB126/kg, or the vehicle, on days 13-19 postconception. In 50-day-old offspring, regardless of the day of exposure to DMBA, only the 7.5 microg group showed statistically significant high levels of PCB126 in the fatty tissue of their mammary glands. Fifty-day-old female offspring of the 250 ng group showed apparent inhibition of the normal differentiation of terminal end buds (TEB) to alveolar buds and lobules (ABL), while those of the 7.5 microg group showed mammary gland hypoplasia. Expression levels of the estrogen receptor-alpha (ER) in TEBs and the ER mRNA in mammary glands were higher in the 7.5 microg, 250 ng, 2.5 ng groups. Proliferating cell nuclear antigen (PCNA) expression in TEBs of 50-day-old rats was statistically significantly higher in the 250 ng group and lower in the 7.5 microg group. In the developing mammary gland, TEBs are considered the most susceptible to mammary carcinogenesis, while ABLs are relatively protected from mammary carcinogenesis. Thus, prenatal exposure to a relatively low dose of PCB126 induced an alteration of mammary gland differentiation that might potentially increase the risk of DMBA-induced mammary carcinoma.