Cadmium exposure increases susceptibility to testicular autoimmunity in mice.

Cadmium, one of various environmental toxicants, is known to suppress systemic immunity and to injure the testicular capillary endothelia with resultant necrosis of testicular tissues in mice and rats treated with high doses. Recently, it also became evident that cadmium can affect the integrity of the blood-testis barrier (BTB), the endocrine function of Leydig cells, apoptosis of germ cells and systemic immunity, even on treatment with a low dose that does not induce spermatogenic disturbance. Experimental autoimmune orchitis (EAO), i.e., an organ-specific autoimmunity of the testis, can be induced by repeated immunization with testicular antigens, and its pathology is characterized by lymphocytic inflammation and spermatogenic disturbance. In the present study, we investigated the morphological and functional changes of testes in mice treated with a low dose of cadmium chloride (CdCl2 ) and also examined its toxicity as to susceptibility to EAO. The results showed that exposure to 3 mg CdCl2 kg(-1) body weight did not affect the spermatogenic state. However, the BTB at the tubuli recti and the rete testis, but not the seminiferous tubules, was slightly weakened, and intra-testicular mRNA expression of interleukin (IL)-6, tumor necrosis factor-α and IL-1ß was significantly increased by the CdCl2 treatment. Furthermore, immunization with testicular antigens after the CdCl2 exposure significantly augmented the EAO severity. Therefore, exposure to a low dose of CdCl2 induces no significant disturbance of spermatogenesis, however, it does change the immunological microcircumstances in the testis, resulting in increased susceptibility to testicular autoimmunity.

Comparison of the changes in temperatures among rural, urban and metropolitan areas around the Inland Sea in Japan.

We investigated the changes in temperatures in Takamatsu, Tadotsu and Osaka areas in Japan. Data of temperatures in Takamatsu (urban area: 1942-2009), Tadotsu (rural area: 1893-2009) and Osaka (metropolitan area: 1883-2009) areas around the Inland Sea in Japan was obtained from Japan Meteorological Agency. The changes in temperatures in three areas in Japan were analyzed and compared. By using data from 1942 to 2009, various parameters of temperatures were significantly correlated with years. The changes in mean temperature in August and in a year in Takamatsu area for 50 years were highest (August: 1.6°C, Year: 1.8°C) among three areas. In addition, correlation coefficient rate between years and the number of days over the level of 34°C in August in Takamatsu area was highest (r = 0.567, p < 0.0001). Parameters of temperatures were gradually increased with years in all three areas. The heat island effect in Takamatsu area was similar to Osaka area in Japan.

Preventive effect of D-psicose, one of rare ketohexoses, on di-(2-ethylhexyl) phthalate (DEHP)-induced testicular injury in rat.

To investigate the preventive effects of d-psicose, one of rare ketohexoses, on di-(2-ethylhexyl) phthalate (DEHP)-induced testicular injury, prepubertal male Sprague-Dawley rats were exposed to DEHP via their diet or orally, while under treatment with d-psicose. The rats given a diet-containing 1% DEHP alone for 7-14 days showed severe testicular atrophy accompanied by aspermatogenesis. On the other hand, those given the diet plus 2% but not 1% d-psicose-supplemented water for 14 days did not develop testicular atrophy, and exhibited an almost complete spermatogenesis. There was no significant difference in plasma mono-(2-ethylhexyl) phthalate (MEHP) levels between the d-psicose-free and d-psicose-treated groups. The testicular malondialdehyde (MDA) level after a single oral administration of 2g/kg of DEHP showed a similar pattern of increase to the plasma MEHP level and peaked in 24h suggesting a close and dose-dependent relation between plasma MEHP and testicular reactive oxygen species (ROS) levels. Pretreatment with d-psicose at a concentration of 2% and 4% resulted in an almost complete but not absolute suppression of testicular MDA production among rats administered 2g/kg of DEHP. The microarray analysis showed the induction of oxidative stress related genes including the thioredoxin, glutathione peroxidase 1 and 2, glutaredoixn 1 after 24h of the DEHP treatment in the testis. These results show that d-psicose prevents DEHP-induced testicular injury by suppressing the generation of ROS in the rat testis. This effect may be due to the direct scavenging by d-psicose of ROS generated in the testis.

Short-term effects of di-(2-ethylhexyl) phthalate on testes, liver, kidneys and pancreas in mice.

AIM: To determine the biochemical effect of di-(2-ethylhexyl) phthalate (DEHP) on testes, liver, kidneys and pancreas on day 10 in the process of degeneration of the seminiferous epithelium. METHODS: Diets containing 2% DEHP were given to male Crlj:CD1(ICR) mice for 10 days. The dose of DEHP was 0.90 +/- 0.52 mg/mouse/day. Their testes, livers, kidneys and pancreata were examined for detection of mono-(2-ethylhexyl) phthalate (MEHP), nitrogen oxides (NOx) produced by peroxidation of nitric oxide (NO) with free radicals, and lipid peroxidation induced by the chain reaction of free radicals. RESULTS: Histological observation and serum analysis showed the presence of severe spermatogenic disturbance, Leydig cell dysfunction, liver dysfunction and dehydration. Unexpectedly, the concentration of MEHP in the testes was extremely low compared with that in the liver. However, the concentration of the NOx in the testes was as high as the hepatic concentration. Furthermore, free radical-induced lipid peroxidation was histochemically detected in the testes but not in the liver. CONCLUSION: The results indicate that DEHP-induced aspermatogenesis is caused by the high sensitivity of the testicular tissues to MEHP rather than the specific accumulation or uptake of circulating MEHP into the testes.

Tentative criteria for assessing workers exposure to toluene by urinary toluene screening.

This study assessed screening thresholds for determining workers exposure to toluene (Tol) by urinary Tol (Tol-U) and proposed applicable criteria for on-site settings. Participants' urine samples (n = 21) were collected at the end of the workday during the latter half of a week and the Tol-U concentration was assayed. Simultaneously, each worker's exposure dose to Tol in the breathing zone during work, Tol-TWA (time-weighted average), was measured. Tentative criteria were proposed. Level I, less than Tol-U 38 microg/l, has the least chance of exceeding Tol-OEL 50 ppm (occupational exposure limit for Tol recommended by the Japan Society for Occupational Health), probability 95% <. Level II, Tol-U 38-60 microg/l, has a low possibility of exceeding Tol-OEL. Level III, Tol-U 60-110 microg/l, has a high possibility of exceeding Tol-OEL. Level IV, more than Tol-U 110 microg/l, clearly exceeds Tol-OEL, probability 95% <.

[Levels of airborne dust by particle size in a suburb of Takamatsu, Japan].

PURPOSE: In recent years, attention has been paid to the influence of the particle fraction < or = 2.5 microns in diameter (PM2.5) among suspended particulate matter (SPM) on health. However, the present status of particle contamination in Japan has hitherto not been adequately clarified. To determine particle contamination in the outdoor air around Kagawa Medical School located on a hill in the suburb of Takamatsu City, we measured SPM according to diameter between February 1999 and January 2000. METHODS: Mass concentrations of SPM were determined using an Andersen air sampler and light scattering counts were measured using a particle counter at the same site. RESULTS: Of the entire year, the total SPM concentration (PM11) was 20-30 mg/m3, and the particle fraction < or = 2.1 microns in diameter (PM2.1) accounted for 25-60%. Both the PM11 and PM2.1 concentrations were the lowest in August when the wind blew mainly from rural areas, but high in January and February when the wind blew mainly from urban areas and April when yellow sand was wind borne from China. The SPM particle count in April was markedly high when a misty aerosol containing yellow sand was extent. The SPM count for each diameter class rapidly decreased after rainfall during passage of storm fronts, but this was especially marked for smaller diameters. During the measurement period in August, air from rural areas often passed the measurement point, and the particle concentration < or = 1 micron in diameter was markedly lower than that in April. CONCLUSION: The results suggest that the SPM levels around Kagawa Medical School located in the suburb of Takamatsu City are associated with seasonal climate and the wind direction from which the prevailing blew.

Possible sources of urinary benzene among nonoccupationally exposed Japanese subjects.

Unmetabolized benzene in urine (U-benzene) is known to be the best marker among the indices for the biological monitoring of occupational and environmental exposure to benzene. In this study, we determined the levels of U-benzene among Japanese university students exposed to benzene nonoccupationally and analyzed the relation between U-benzene levels and the possible factors responsible for environmental benzene exposure. In urinalysis, U-benzene concentration among 124 students was detected in the range from 18 (minimum detection limit) to 249 ng/l. The frequency distribution of U-benzene concentration peaked at 0-19 ng/l. Mean and median values of 40 and 20 ng/l for U-benzene concentration in nonoccupationally exposed subjects were lower than those in a previous study. Stepwise multiple linear regression analysis was performed to assess the potential sources of exposure to environmental benzene by analyzing the relation between U-benzene and personal, behavioral, and environmental factors. The results showed that only smoking habit (P < 0.01) and residential house age (P < 0.05) were independent determinants of U-benzene levels. In addition, U-benzene levels in relation to smoking and house age suggested that these factors could be associated with the synergistic elevation of U-benzene. The present study showed U-benzene levels among non-occupationally exposed Japanese subjects and revealed that the major exposure sources to benzene in the general environment were tobacco smoking and indoor air contamination.

Investigation of indoor air pollution by chlorpyrifos: Determination of chlorpyrifos in indoor air and 3,5,6-trichloro-2-pyridinol in residents' urine as an exposure index.

OBJECTS: We carried out an investigation to clarify the real state of indoor air pollution by chlorpyrifos (termiticide) and exposure to chlorpyrifos of residents by measuring its urinary metabolite 3,5,6-trichloro-2-pyridinol (TCP) as an exposure index, such as biological monitoring. METHODS: The investigation was conducted in 43 individual houses with termiticide application (whether the termiticide was chlorpyrifos is uncertain) and 3 control houses without any termiticide application in Kagawa, Japan. Urine samples were collected from 46 healthy adult residents of the aforementioned houses. RESULTS: Chlorpyrifos in indoor air in the control houses was not detected (ND<1 ng/m(3), n=3), while 41 of 43 houses with termiticide application showed 1-350 ng/m(3). Although the chlorpyrifos concentrations in these 41 houses did not exceeded the indoor air quality guideline of 1000 ng/m(3), but 3 houses were higher than the guideline 100 ng/m(3) for children in Japan. Urinary TCP concentrations of 0.1-7.8 ng/mg·creatinine were detected in 41 residents from the 41 houses where chlorpyrifos had been detected. The chlorpyrifos concentration and the urinary TCP revealed a positive correlation (r=0.5468, p<0.01, n=41). CONCLUSIONS: The immediate health hazard from air born chlorpyrifos in the examined houses was negligible, but the findings suggest that it is necessary to monitor chemicals which may contaminate indoor air and to assess the risk of prolonged exposure to such chemicals. The measuring of urinary metabolite TCP of chlorpyrifos via biological monitoring would be useful, allowing comprehensive evaluation of the exposure to chlorpyrifos in indoor air.

Di-(2-ethylhexyl) phthalate induces severe aspermatogenesis in mice, however, subsequent antioxidant vitamins supplementation accelerates regeneration of the seminiferous epithelium.

Di-(2-ethylhexyl) phthalate (DEHP), now regarded as an endocrine disruptor, can experimentally induce spermatogenic disturbance in laboratory animals. Our previous study demonstrated that antioxidant vitamins (vitamins C and E) supplementation during DEHP-treatment significantly protected the rat seminiferous epithelium from DEHP-gonadotoxicity. In the present study, we gave these antioxidant vitamins to mice already having fully developed aspermatogenesis because of DEHP to determine whether or not the vitamins can cure the injured seminiferous epithelium. CD-1 male mice were fed on a DEHP-containing diet for 15 days and then fed on the DEHP-free normal diet with or without supplementation of vitamins C and E in drinking water for another 50 days. The results showed that severe aspermatogenesis was induced by the DEHP-treatment but that the damaged seminiferous epithelium spontaneously recovered whether the vitamins were provided or not. This indicates that the DEHP-induced aspermatogenesis was reversible. However, the supplementation of antioxidant vitamins significantly accelerated regeneration of the injured seminiferous epithelium, suggesting that the vitamins have a therapeutic effect on DEHP-induced aspermatogenesis.