2 Bromopropane

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Gaku Ichihara - One of the best experts on this subject based on the ideXlab platform.

  • melatonin pretreatment attenuates 2 Bromopropane induced testicular toxicity in rats
    Toxicology, 2009
    Co-Authors: Fen Huang, Huan Ning, Qianqian Xin, Yong Huang, Hua Wang, Zhihua Zhang, Gaku Ichihara
    Abstract:

    2-Bromopropane (2-BP) was used as an alternative for ozone-depleting solvents, which caused reproductive disorders in male workers and laboratory animals. A recent study indicated that 2-BP impaired antioxidant cellular defences and enhanced lipid peroxidation (LPO). Melatonin is a powerful endogenous antioxidant. We hypothesized that reactive oxygen species (ROS) and lipid peroxidation are involved in 2-BP-induced testicular toxicities. To test the hypothesis, we investigated the effects of melatonin on 2-BP-induced testicular toxicities. Rats were intraperitoneally injected with 2-BP (1 g/kg) with or without melatonin (5 mg/kg), then sacrificed on 7th day after 2-BP injection. Epididymal and testicular tissues were examined for biochemical and histopathological changes. Apoptotic cells in testis were detected by TUNEL staining and immunohistochemistry for active caspase-3. Exposure to 2-BP significantly decreased epididymal sperm count and morphological normal sperms. 2-BP also induced vacuolation and atrophy of the seminiferous tubules, reduction of spermatogonia and apoptosis of germ cells. 2-BP significantly increased TBARS levels in plasma and epididymis, and decreased GSH content in testis and epididymis. Pretreatment with melatonin counteracted 2-BP-induced oxidative stress, ameliorated apoptosis in testis and attenuated histopathological damage in testis. In addition, pretreatment with melatonin significantly attenuated 2-BP-induced sperm morphological changes. We conclude that pretreatment with melatonin attenuates 2-BP-induced testicular toxicity through its ROS scavenging and anti-apoptotic effects.

  • Neuro-reproductive toxicities of 1-Bromopropane and 2-Bromopropane
    International Archives of Occupational and Environmental Health, 2005
    Co-Authors: Gaku Ichihara
    Abstract:

    2-Bromopropane was used as an alternative to chlorofluorocarbons in a Korean electronics factory and caused reproductive and hematopoietic disorders in male and female workers. This causality was revealed by animal studies, and target cells were identified in subsequent studies. After identification of 2-Bromopropane toxicity, 1-Bromopropane was introduced to the workplace as a new alternative to ozone-depleting solvents. 1-Bromopropane was considered less mutagenic than 2-Bromopropane, but, in contrast, animal experiments revealed that 1-Bromopropane is a potent neurotoxic compound compared with 2-Bromopropane. It was also revealed that 1-Bromopropane has reproductive toxicity, but the target cells are different from those of 2-Bromopropane. Exposure to 1-Bromopropane inhibits spermiation in male rats and disrupts the development of follicles in female rats, in contrast to 2-Bromopropane, which targets spermatogonia and oocytes in primordial follicles. After the first animal study describing the neurotoxicity of 1-Bromopropane, human cases were reported. Those cases showed decreased sensation of vibration and perception, paresthesia in the lower extremities, decreased sensation in the ventral aspects of the thighs and gluteal regions, stumbling and headache, as well as mucosal irritation, as the initial symptoms. The dose–response of Bromopropanes in humans and mechanism(s) underlying the differences in the toxic effects of the two Bromopropanes remain to be determined.

  • involvement of bcl 2 family genes and fas signaling system in primary and secondary male germ cell apoptosis induced by 2 Bromopropane in rat
    Toxicology and Applied Pharmacology, 2001
    Co-Authors: Hisayo Kubota, Gaku Ichihara, Yasuhiro Takeuchi, Junzo Saegusa, Ruisheng Wang, Yasutake Ogawa, Naomi Hisanaga
    Abstract:

    Epidemiological surveys and animal experimental studies suggest that exposure to 2-Bromopropane (2-BP) could result in reproductive and hematopoietic disorders. The objectives of this study were to investigate the role of apoptosis in 2-BP-induced testicular toxicity and whether this process involves Bcl-2 family genes and the Fas signaling system. Rats were injected percutaneously with 1350 mg/kg 2-BP for 1 to 5 days and then were euthanized at 6 or 12 h after one dose, 6 h after two, three, or five doses, and 2 or 9 days after the final treatment. Light and electron microscopic analyses, TUNEL staining of DNA fragments, agarose gel electrophoresis of low-molecular-weight DNA, and Western blotting analysis of Bcl-2 family proteins and Fas receptor and ligand were conducted. Two-day treatment resulted in selective degeneration of spermatogonia with marked nuclear chromatin condensation. DNA ladder formation on the agarose gel further validated the findings of TUNEL-stained apoptotic cells. The percentage of apoptotic-positive tubules and apoptotic cell index increased time dependently. 2-BP treatment resulted in two distinct morphological changes: an immediate effect on spermatogonia and secondary apoptosis of spermatocytes 9 days after treatment. Downregulation of Bcl-2 after the first or second injection of 2-BP and upregulation of Bax after the first treatment contributed to the initiation of primary apoptosis of spermatogonia. Expression of FasL was inhibited while expression of Fas increased after the 2-BP treatment and remained at levels about two times of the control. However, it increased about sixfold of the control by day 9 after final injection, which contributed to the induction of secondary apoptosis of spermatocytes. Our results indicate that 2-BP resulted in apoptotic death of testicular germ cells and that this process involves the Bcl-2 family genes and the Fas signaling system.

  • Neurotoxicity of 2-Bromopropane and 1-Bromopropane, alternative solvents for chlorofluorocarbons.
    Environmental research, 2001
    Co-Authors: Gaku Ichihara, Eiji Shibata, Junzoh Kitoh, Zhenlin Xie, Michihiro Kamijima, Yasuhiro Takeuchi
    Abstract:

    To clarify the neurotoxicity of 2-Bromopropane (2-BP) in comparison with 1-Bromopropane (1-BP), 36 Wistar strain male rats were divided into 4 groups of 9 and exposed daily to 100-ppm 2-BP, 1000-ppm 2-BP, 1000-ppm 1-BP, or fresh air for 8 h a day. Exposure to 1000 ppm of 1-BP was discontinued after 5 or 7 weeks' exposure because of the unexpected appearance of incomplete hindlimb paralysis followed by serious emaciation. The other groups were sacrificed at the end of 12 weeks' exposure. Exposure to 1000 ppm of 2-BP resulted in significant decreases in body weight and motor nerve conduction velocity (MCV) and elongation in distal latency (DL). A ball-like enlargement of myelin sheaths was observed. Significant reductions in the number of erythrocytes, platelets, and leukocytes, testicular germ cell loss, and seminiferous atrophy were also observed in this group, but not in 100-ppm 2-BP group. Exposure to 1000 ppm of 1-BP for 5 or 7 weeks caused a significant decrease in body weight and MCV and elongation in DL. Linearly arranged ovoid- or bubble-like debris of the axons and myelin sheaths in the teased tibial nerves and axonal swelling in gracilis nucleus were found in this group. No significant changes in hematological indices or histopathological findings of the testis were found in this group. In conclusion, 2-BP is neurotoxic to the peripheral nerves in addition to its toxic effects on the reproductive and hematopoietic systems at 1000 ppm. No noticeable changes were found in the rats exposed to 100 ppm of 2-BP. 1-BP is a potent neurotoxicant at 1000 ppm for 5 or 7 weeks, while testicular and hematopoietic toxicity was not found.

  • 2 Bromopropane causes ovarian dysfunction by damaging primordial follicles and their oocytes in female rats
    Toxicology and Applied Pharmacology, 1999
    Co-Authors: Gaku Ichihara, Eiji Shibata, Junzoh Kitoh, Zhenlin Xie, Michihiro Kamijima, Naomi Hisanaga, Yasuhiro Takeuchi
    Abstract:

    Ovarian dysfunction induced by 2-Bromopropane (2-BP) has been described in female factory workers and experimental animals. However, the underlying mechanism is still unclear. To establish the reproductive target site and define mechanisms of 2-BP toxicity in adult female rats, we examined the effects of different doses and duration of exposure to 2-BP in female rats. In the dose-dependent experiments, female rats were exposed to 2-BP at 100, 300, or 1000 ppm or fresh air (n = 9 each) in exposure chambers for 8 h/day for 9 weeks. In the time-course experiments, female rats were exposed to 2-BP at 3000 ppm for 8 h (n = 7 each). The rats were then euthanized 1, 3, 5, and 17 days after exposure. Differential follicle counts and in situ terminal deoxynucleotidyl transferase assay were used to evaluate 2-BP effect on primordial, growing, and antral follicles. Exposure to 2-BP at 300 and 1000 ppm produced a significant reduction in the percentage of primordial, growing, and antral follicles in a dose-dependent manner. Significant reduction in the percentage of primordial follicles at 17 days after exposure was observed in time-course experiments. Exposure to 2-BP at 3000 ppm for 8 h resulted in histological changes in primordial follicles complex at 5 and 17 days after exposure. These changes consisted of distortion of the symmetry of oocytes and their nuclei at Day 5 after exposure and appearance of eccentric pyknotic cells and shrinkage of oocyte nuclei at Day 17 after exposure. In situ end labeling showed increased numbers of apoptotic oocytes and granulosa cells in primordial follicles at Days 5 and 17 after exposure. Our results suggested that ovarian dysfunction induced by 2-BP was caused by the destruction of primordial follicle and its oocyte due to the induction of apoptosis. Our studies also show that the follicle differential count is a more sensitive method than the vaginal smear in monitoring the female reproductive disorders induced by 2-BP.

Yasuhiro Takeuchi - One of the best experts on this subject based on the ideXlab platform.

  • involvement of bcl 2 family genes and fas signaling system in primary and secondary male germ cell apoptosis induced by 2 Bromopropane in rat
    Toxicology and Applied Pharmacology, 2001
    Co-Authors: Hisayo Kubota, Gaku Ichihara, Yasuhiro Takeuchi, Junzo Saegusa, Ruisheng Wang, Yasutake Ogawa, Naomi Hisanaga
    Abstract:

    Epidemiological surveys and animal experimental studies suggest that exposure to 2-Bromopropane (2-BP) could result in reproductive and hematopoietic disorders. The objectives of this study were to investigate the role of apoptosis in 2-BP-induced testicular toxicity and whether this process involves Bcl-2 family genes and the Fas signaling system. Rats were injected percutaneously with 1350 mg/kg 2-BP for 1 to 5 days and then were euthanized at 6 or 12 h after one dose, 6 h after two, three, or five doses, and 2 or 9 days after the final treatment. Light and electron microscopic analyses, TUNEL staining of DNA fragments, agarose gel electrophoresis of low-molecular-weight DNA, and Western blotting analysis of Bcl-2 family proteins and Fas receptor and ligand were conducted. Two-day treatment resulted in selective degeneration of spermatogonia with marked nuclear chromatin condensation. DNA ladder formation on the agarose gel further validated the findings of TUNEL-stained apoptotic cells. The percentage of apoptotic-positive tubules and apoptotic cell index increased time dependently. 2-BP treatment resulted in two distinct morphological changes: an immediate effect on spermatogonia and secondary apoptosis of spermatocytes 9 days after treatment. Downregulation of Bcl-2 after the first or second injection of 2-BP and upregulation of Bax after the first treatment contributed to the initiation of primary apoptosis of spermatogonia. Expression of FasL was inhibited while expression of Fas increased after the 2-BP treatment and remained at levels about two times of the control. However, it increased about sixfold of the control by day 9 after final injection, which contributed to the induction of secondary apoptosis of spermatocytes. Our results indicate that 2-BP resulted in apoptotic death of testicular germ cells and that this process involves the Bcl-2 family genes and the Fas signaling system.

  • Neurotoxicity of 2-Bromopropane and 1-Bromopropane, alternative solvents for chlorofluorocarbons.
    Environmental research, 2001
    Co-Authors: Gaku Ichihara, Eiji Shibata, Junzoh Kitoh, Zhenlin Xie, Michihiro Kamijima, Yasuhiro Takeuchi
    Abstract:

    To clarify the neurotoxicity of 2-Bromopropane (2-BP) in comparison with 1-Bromopropane (1-BP), 36 Wistar strain male rats were divided into 4 groups of 9 and exposed daily to 100-ppm 2-BP, 1000-ppm 2-BP, 1000-ppm 1-BP, or fresh air for 8 h a day. Exposure to 1000 ppm of 1-BP was discontinued after 5 or 7 weeks' exposure because of the unexpected appearance of incomplete hindlimb paralysis followed by serious emaciation. The other groups were sacrificed at the end of 12 weeks' exposure. Exposure to 1000 ppm of 2-BP resulted in significant decreases in body weight and motor nerve conduction velocity (MCV) and elongation in distal latency (DL). A ball-like enlargement of myelin sheaths was observed. Significant reductions in the number of erythrocytes, platelets, and leukocytes, testicular germ cell loss, and seminiferous atrophy were also observed in this group, but not in 100-ppm 2-BP group. Exposure to 1000 ppm of 1-BP for 5 or 7 weeks caused a significant decrease in body weight and MCV and elongation in DL. Linearly arranged ovoid- or bubble-like debris of the axons and myelin sheaths in the teased tibial nerves and axonal swelling in gracilis nucleus were found in this group. No significant changes in hematological indices or histopathological findings of the testis were found in this group. In conclusion, 2-BP is neurotoxic to the peripheral nerves in addition to its toxic effects on the reproductive and hematopoietic systems at 1000 ppm. No noticeable changes were found in the rats exposed to 100 ppm of 2-BP. 1-BP is a potent neurotoxicant at 1000 ppm for 5 or 7 weeks, while testicular and hematopoietic toxicity was not found.

  • 2 Bromopropane causes ovarian dysfunction by damaging primordial follicles and their oocytes in female rats
    Toxicology and Applied Pharmacology, 1999
    Co-Authors: Gaku Ichihara, Eiji Shibata, Junzoh Kitoh, Zhenlin Xie, Michihiro Kamijima, Naomi Hisanaga, Yasuhiro Takeuchi
    Abstract:

    Ovarian dysfunction induced by 2-Bromopropane (2-BP) has been described in female factory workers and experimental animals. However, the underlying mechanism is still unclear. To establish the reproductive target site and define mechanisms of 2-BP toxicity in adult female rats, we examined the effects of different doses and duration of exposure to 2-BP in female rats. In the dose-dependent experiments, female rats were exposed to 2-BP at 100, 300, or 1000 ppm or fresh air (n = 9 each) in exposure chambers for 8 h/day for 9 weeks. In the time-course experiments, female rats were exposed to 2-BP at 3000 ppm for 8 h (n = 7 each). The rats were then euthanized 1, 3, 5, and 17 days after exposure. Differential follicle counts and in situ terminal deoxynucleotidyl transferase assay were used to evaluate 2-BP effect on primordial, growing, and antral follicles. Exposure to 2-BP at 300 and 1000 ppm produced a significant reduction in the percentage of primordial, growing, and antral follicles in a dose-dependent manner. Significant reduction in the percentage of primordial follicles at 17 days after exposure was observed in time-course experiments. Exposure to 2-BP at 3000 ppm for 8 h resulted in histological changes in primordial follicles complex at 5 and 17 days after exposure. These changes consisted of distortion of the symmetry of oocytes and their nuclei at Day 5 after exposure and appearance of eccentric pyknotic cells and shrinkage of oocyte nuclei at Day 17 after exposure. In situ end labeling showed increased numbers of apoptotic oocytes and granulosa cells in primordial follicles at Days 5 and 17 after exposure. Our results suggested that ovarian dysfunction induced by 2-BP was caused by the destruction of primordial follicle and its oocyte due to the induction of apoptosis. Our studies also show that the follicle differential count is a more sensitive method than the vaginal smear in monitoring the female reproductive disorders induced by 2-BP.

  • effect of inhalation exposure to 2 Bromopropane on the nervous system in rats
    Toxicology, 1999
    Co-Authors: Gaku Ichihara, Eiji Shibata, Junzoh Kitoh, Zhenlin Xie, Michihiro Kamijima, Nobuyuki Asaeda, Naomi Hisanaga, Yasuhiro Takeuchi
    Abstract:

    Exposure to 2-Bromopropane (2-BP) is suspected to have adverse effects on the nervous system. The aim of this study was to investigate whether the exposure of rats to 2-BP had neurotoxic effects using histological and electrophysiological studies. Wistar strain male rats were exposed daily to either 100 or 1000 ppm 2-BP or to fresh air for 8 h a day for 12 weeks. Body weight was measured before exposure and every 2 weeks. Motor nerve conduction velocity (MCV) and distal latency (DL) were measured before exposure and every 4 weeks during exposure. Histological examination of the nervous system was also performed. Exposure of rats (n = 9) to 1000 ppm resulted in suppression of body weight gain and a significant decrease in brain weight compared to the control (n = 9). Electrophysiological measurements showed a significant decrease in MCV in 1000 ppm exposed rats at 8 weeks and significant prolongation of DL at 8 and 12 weeks. Abnormalities of the myelin sheath were detected in the common peroneal nerves. In 100-ppm exposed rats (n = 9), no significant changes were noted in body weight and the peripheral nerve. In conclusions, long-term exposure to 1000 ppm of 2-BP may result in peripheral neuropathy in rats.

  • occupational health survey on workers exposed to 2 Bromopropane at low concentrations
    American Journal of Industrial Medicine, 1999
    Co-Authors: Gaku Ichihara, Michihiro Kamijima, Xuncheng Ding, Simeng Peng, Xuezhi Jiang, Yasuhiro Takeuchi
    Abstract:

    Background Recent case studies in Korea and animal studies revealed the reproductive and hematopoietic toxicity of 2-Bromopropane introduced into workplaces as an alternative to ozone-layer depleting chlorofluorocarbons. We aimed to clarify the dose-effect relationship of 2-Bromopropane in workers. Method The exposure concentration of 2-Bromopropane and hematological indices, hormonal levels, menstruation status, and sperm indices were examined in 25 workers (11 males, 14 females) at a 2-Bromopropane factory. Regression analyses of the examined indices against time-weighted average (TWA) of exposure concentration were conducted. Results Amenorrhea or polymenorrhea was observed only in older females. Hematological indices had a significant relation with TWA of exposure concentration in females with normal menstruation. However, no other indices showed any significant relation with TWA of 2-Bromopropane. Conclusions No severe cases of reproductive or hematopoietic disorders were found at less than 10 ppm (TWA), but a possible adverse effect of 2-Bromopropane on hematopoiesis could not be disproved.

Michihiro Kamijima - One of the best experts on this subject based on the ideXlab platform.

  • Neurotoxicity of 2-Bromopropane and 1-Bromopropane, alternative solvents for chlorofluorocarbons.
    Environmental research, 2001
    Co-Authors: Gaku Ichihara, Eiji Shibata, Junzoh Kitoh, Zhenlin Xie, Michihiro Kamijima, Yasuhiro Takeuchi
    Abstract:

    To clarify the neurotoxicity of 2-Bromopropane (2-BP) in comparison with 1-Bromopropane (1-BP), 36 Wistar strain male rats were divided into 4 groups of 9 and exposed daily to 100-ppm 2-BP, 1000-ppm 2-BP, 1000-ppm 1-BP, or fresh air for 8 h a day. Exposure to 1000 ppm of 1-BP was discontinued after 5 or 7 weeks' exposure because of the unexpected appearance of incomplete hindlimb paralysis followed by serious emaciation. The other groups were sacrificed at the end of 12 weeks' exposure. Exposure to 1000 ppm of 2-BP resulted in significant decreases in body weight and motor nerve conduction velocity (MCV) and elongation in distal latency (DL). A ball-like enlargement of myelin sheaths was observed. Significant reductions in the number of erythrocytes, platelets, and leukocytes, testicular germ cell loss, and seminiferous atrophy were also observed in this group, but not in 100-ppm 2-BP group. Exposure to 1000 ppm of 1-BP for 5 or 7 weeks caused a significant decrease in body weight and MCV and elongation in DL. Linearly arranged ovoid- or bubble-like debris of the axons and myelin sheaths in the teased tibial nerves and axonal swelling in gracilis nucleus were found in this group. No significant changes in hematological indices or histopathological findings of the testis were found in this group. In conclusion, 2-BP is neurotoxic to the peripheral nerves in addition to its toxic effects on the reproductive and hematopoietic systems at 1000 ppm. No noticeable changes were found in the rats exposed to 100 ppm of 2-BP. 1-BP is a potent neurotoxicant at 1000 ppm for 5 or 7 weeks, while testicular and hematopoietic toxicity was not found.

  • 2 Bromopropane causes ovarian dysfunction by damaging primordial follicles and their oocytes in female rats
    Toxicology and Applied Pharmacology, 1999
    Co-Authors: Gaku Ichihara, Eiji Shibata, Junzoh Kitoh, Zhenlin Xie, Michihiro Kamijima, Naomi Hisanaga, Yasuhiro Takeuchi
    Abstract:

    Ovarian dysfunction induced by 2-Bromopropane (2-BP) has been described in female factory workers and experimental animals. However, the underlying mechanism is still unclear. To establish the reproductive target site and define mechanisms of 2-BP toxicity in adult female rats, we examined the effects of different doses and duration of exposure to 2-BP in female rats. In the dose-dependent experiments, female rats were exposed to 2-BP at 100, 300, or 1000 ppm or fresh air (n = 9 each) in exposure chambers for 8 h/day for 9 weeks. In the time-course experiments, female rats were exposed to 2-BP at 3000 ppm for 8 h (n = 7 each). The rats were then euthanized 1, 3, 5, and 17 days after exposure. Differential follicle counts and in situ terminal deoxynucleotidyl transferase assay were used to evaluate 2-BP effect on primordial, growing, and antral follicles. Exposure to 2-BP at 300 and 1000 ppm produced a significant reduction in the percentage of primordial, growing, and antral follicles in a dose-dependent manner. Significant reduction in the percentage of primordial follicles at 17 days after exposure was observed in time-course experiments. Exposure to 2-BP at 3000 ppm for 8 h resulted in histological changes in primordial follicles complex at 5 and 17 days after exposure. These changes consisted of distortion of the symmetry of oocytes and their nuclei at Day 5 after exposure and appearance of eccentric pyknotic cells and shrinkage of oocyte nuclei at Day 17 after exposure. In situ end labeling showed increased numbers of apoptotic oocytes and granulosa cells in primordial follicles at Days 5 and 17 after exposure. Our results suggested that ovarian dysfunction induced by 2-BP was caused by the destruction of primordial follicle and its oocyte due to the induction of apoptosis. Our studies also show that the follicle differential count is a more sensitive method than the vaginal smear in monitoring the female reproductive disorders induced by 2-BP.

  • effect of inhalation exposure to 2 Bromopropane on the nervous system in rats
    Toxicology, 1999
    Co-Authors: Gaku Ichihara, Eiji Shibata, Junzoh Kitoh, Zhenlin Xie, Michihiro Kamijima, Nobuyuki Asaeda, Naomi Hisanaga, Yasuhiro Takeuchi
    Abstract:

    Exposure to 2-Bromopropane (2-BP) is suspected to have adverse effects on the nervous system. The aim of this study was to investigate whether the exposure of rats to 2-BP had neurotoxic effects using histological and electrophysiological studies. Wistar strain male rats were exposed daily to either 100 or 1000 ppm 2-BP or to fresh air for 8 h a day for 12 weeks. Body weight was measured before exposure and every 2 weeks. Motor nerve conduction velocity (MCV) and distal latency (DL) were measured before exposure and every 4 weeks during exposure. Histological examination of the nervous system was also performed. Exposure of rats (n = 9) to 1000 ppm resulted in suppression of body weight gain and a significant decrease in brain weight compared to the control (n = 9). Electrophysiological measurements showed a significant decrease in MCV in 1000 ppm exposed rats at 8 weeks and significant prolongation of DL at 8 and 12 weeks. Abnormalities of the myelin sheath were detected in the common peroneal nerves. In 100-ppm exposed rats (n = 9), no significant changes were noted in body weight and the peripheral nerve. In conclusions, long-term exposure to 1000 ppm of 2-BP may result in peripheral neuropathy in rats.

  • occupational health survey on workers exposed to 2 Bromopropane at low concentrations
    American Journal of Industrial Medicine, 1999
    Co-Authors: Gaku Ichihara, Michihiro Kamijima, Xuncheng Ding, Simeng Peng, Xuezhi Jiang, Yasuhiro Takeuchi
    Abstract:

    Background Recent case studies in Korea and animal studies revealed the reproductive and hematopoietic toxicity of 2-Bromopropane introduced into workplaces as an alternative to ozone-layer depleting chlorofluorocarbons. We aimed to clarify the dose-effect relationship of 2-Bromopropane in workers. Method The exposure concentration of 2-Bromopropane and hematological indices, hormonal levels, menstruation status, and sperm indices were examined in 25 workers (11 males, 14 females) at a 2-Bromopropane factory. Regression analyses of the examined indices against time-weighted average (TWA) of exposure concentration were conducted. Results Amenorrhea or polymenorrhea was observed only in older females. Hematological indices had a significant relation with TWA of exposure concentration in females with normal menstruation. However, no other indices showed any significant relation with TWA of 2-Bromopropane. Conclusions No severe cases of reproductive or hematopoietic disorders were found at less than 10 ppm (TWA), but a possible adverse effect of 2-Bromopropane on hematopoiesis could not be disproved.

  • a review on toxicity of 2 Bromopropane mainly on its reproductive toxicity
    Journal of Occupational Health, 1997
    Co-Authors: Yasuhiro Takeuchi, Gaku Ichihara, Michihiro Kamijima
    Abstract:

    A Review on Toxicity of 2-Bromopropane: Mainly on its Reproductive Toxicity: Yasuhiro TAKEUCHI, et al. Department of Hygiene, Nagoya University School of Medicine—2-Bromopropane has been used mostly as an intermediate for medicines, pesticides and other chemicals in closed systems. Recently it has come to be used as an alternative solvent in open systems instead of ozone layer depleting chlorofluorocarbons. An outbreak of reproductive and hematopoietic disorders occurred in workers exposed to solvents containing 2-Bromopropane in a Korean factory in 1995. After that some animal experiments revealed that 2-Bromopropane has a severe toxic effect on the female and male reproductive organs and hematopoietic organs. We reviewed the toxicity of 2-Bromopropane based on the recent data obtained in epidemiological surveys and animal experiments. Toxicities of structurally related Bromopropanes were compared with that of 2-Bromopropane and its risk assessment was discussed. The conclusions are as follows: 1. 2-Bromopropane has a specific reproductive and hematopoietic toxicity in both sexes in humans and experimental animals. 2. It could impair the testes, especially spermatogonia in males. 3. It could impair the ovarian function, resulting in a disturbed estrous cycle and loss of oocytes in females. 4. It could impair the bone marrow, resulting in pancytopenia. 5. It has a weak potent mutagenicity in bacterial mutation assays. 6. A risk assessment suggests that around 0.3-10 ppm might be recommended as an occupational exposure limit for 2-Bromopropane.

Lei Zhao - One of the best experts on this subject based on the ideXlab platform.

  • densities viscosities and excess properties of 2 Bromopropane methanol binary mixtures at temperature from 298 15 to 318 15 k
    Journal of The Korean Chemical Society, 2010
    Co-Authors: Zhen Zhang, Lei Zhao
    Abstract:

    ABSTRACT. The densities and viscosities of 2-Bromopropane-methanol binary mixtures had been determined using an digital vibratingU-tube densimeter and Ubbelohde capillary viscometer respectively from (298.15 to 318.15) K. The dependence of densities and vi s-cosities on temperature and concentration had been correlated. The excess molar volume and the excess viscosity of the binary s ystemwere calculated from the experimental density and viscosity data. The excess molar volumes were related to compositions by polynomialregression and regression parameters and total RMSD deviations were obtained; the excess viscosities was related to composition s byRedlich-Kister equation and regression coefficients and total RMSD deviation of the excess viscosity for 2-Bromopropane and met hanolbinary system were obtained. The results showed that the model agreed very well with the experimental data. Keywords: Densities, Viscosities, Excess molar volume, Excess viscosity, 2-Bromopropane, Methanol 298.15 ~ 318.15 K

  • measurement and correlation for solubility of 2 Bromopropane and thiourea in water
    Journal of Chemical & Engineering Data, 2009
    Co-Authors: Feng Guo, Lei Zhao
    Abstract:

    The solubility of 2-Bromopropane and thiourea in water had been determined from (295.25 to 354.75) K by analytical and synthetic methods, respectively. The experimental data were correlated with the modified Apelblat equation and quadratic equation separately. The solubilities correlated by the model show good agreement with experimental data.

  • Densities, Viscosities and Excess Properties of 2-Bromopropane- Methanol Binary Mixtures at Temperature from (298.15 to 318.15) K
    2009
    Co-Authors: Lei Zhao, Zhen Zhang
    Abstract:

    ABSTRACT. The densities and viscosities of 2-Bromopropane-methanol binary mixtures had been determined using an digital vibrating U-tube densimeter and Ubbelohde capillary viscometer respectively from (298.15 to 318.15) K. The dependence of densities and vis-cosities on temperature and concentration had been correlated. The excess molar volume and the excess viscosity of the binary system were calculated from the experimental density and viscosity data. The excess molar volumes were related to compositions by polynomial regression and regression parameters and total RMSD deviations were obtained; the excess viscosities was related to compositions by Redlich-Kister equation and regression coefficients and total RMSD deviation of the excess viscosity for 2-Bromopropane and methanol binary system were obtained. The results showed that the model agreed very well with the experimental data

Wen-hsiung Chan - One of the best experts on this subject based on the ideXlab platform.

  • www.mdpi.com/journal/ijms Cytotoxic Effects of 2-Bromopropane on Embryonic Development in Mouse Blastocysts
    2013
    Co-Authors: Wen-hsiung Chan
    Abstract:

    Abstract: 2-Bromopropane (2-BP), an alternative to ozone-depleting solvents, is used as a cleaning solvent. Here, we examined the cytotoxic effects of 2-Bromopropane (2-BP) on mouse embryos at the blastocyst stage, subsequent embryonic attachment and outgrowth in vitro, and in vivo implantation via embryo transfer. Mouse blastocysts were incubated in medium with or without 2-BP (2.5, 5 or 10 μM) for 24 h. Cell proliferation and growth were investigated with dual differential staining, apoptosis was analyzed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) analysis, and implantation and post-implantation development of embryos were assessed using in vitro development analysis and in vivo embryo transfer, respectively. Blastocysts treated with 5 or 10 μM 2-BP displayed significantly increased apoptosis, and decreased inner cell mass (ICM) and trophectoderm (TE) cell number. Additionally, the implantation success rates of 2-BP-pretreated blastocysts were lower than those of untreated controls. In vitro treatment with 5 or 10 μM 2-BP was associated with increased resorption of postimplantation embryos, and decreased placental and fetal weights. Our results collectively indicate that in vitro exposure to 2-BP induces apoptosis, suppresses implantation rates after transfer to host mice, and retards early postimplantation development

  • Hazardous apoptotic effects of 2-Bromopropane on maturation of mouse oocytes, fertilization, and fetal
    2013
    Co-Authors: Wen-hsiung Chan
    Abstract:

    Abstract: 2-Bromopropane (2-BP) is used as an alternative to ozone-depleting cleaning solvents. Previously, we reported that 2-BP has cytotoxic effects on mouse blastocysts and is associated with defects in subsequent development. Here, we further investigate the effects of 2-BP on oocyte maturation and subsequent pre- and post-implantation development, both in vitro and in vivo. Notably, 2-BP induced a significant reduction in the rates of oocyte maturation, fertilization, and in vitro embryonic development. Treatment of oocytes with 2-BP during in vitro maturation (IVM) resulted in increased resorption of postimplantation embryos and decreased fetal weights. Experiments with a mouse model disclosed that consumption of drinking water containing 20 μM 2-BP led to decreased oocyte maturation in vivo and fertilization in vitro, as well as impairment of early embryonic development. Interestingly, pretreatment with a caspase-3-specific inhibitor effectively prevented 2-BP-triggered hazardous effects, suggesting that embryonic impairment by 2-BP occurs via a caspase-dependent apoptotic process. A study using embryonic stem cells as the assay model conclusively demonstrated that 2-BP induces cell death processes through apoptosis and not necrosis, and inhibits early embryo development in mouse embryonic stem cells. These results collectively confirm the hazardous effects of 2-BP on embryos derived from pretreated oocytes

  • impact of 2 Bromopropane on mouse embryonic stem cells and related regulatory mechanisms
    African Journal of Biotechnology, 2013
    Co-Authors: Imeng Huang, Wen-hsiung Chan
    Abstract:

    2-Bromopropane (2-BP), a cleaning agent, is used as an alternative to ozone-depleting solvents. Previously, 2-BP was shown to have cytotoxic effects on mouse blastocysts and is associated with defects in their subsequent development, both in vitro and in vivo. In addition, it was found that 2-BP also has cytotoxic effects on oocyte maturation and subsequent pre- and post implantation development in vitro and in vivo, and significantly reduces the rate of oocyte maturation, fertilization, and embryonic development in vitro. This study shows that 2-BP (5 to 10 μM) induces apoptotic processes in mouse embryonic stem cells (ESC-B5), but exerts no effects at treatment dosages below 5 μM. In ESC-B5 cells, 2-BP directly increased the content of reactive oxygen species (ROS), significantly increased the cytoplasmic free calcium and nitric oxide (NO) levels, triggered a loss of mitochondrial membrane potential (MMP), activated caspases-9 and -3, and induced cell death. Pre-treatment with NO scavengers suppressed the apoptotic biochemical changes induced by 10 μM 2-BP and promoted the gene expression levels of p53 and p21, which are involved in apoptotic signaling. These results demonstrate for the first time that 2-BP triggers apoptosis in mouse embryonic stem cells via ROS, NO and the activation of mitochondria-dependent cell death signaling.

  • resveratrol protects against hazardous effects of 2 Bromopropane on maturation of mouse oocytes fertilization and fetal development
    African Journal of Biotechnology, 2012
    Co-Authors: Imeng Huang, Wen-hsiung Chan
    Abstract:

    2-Bromopropane (2-BP) is regularly used as an alternative to ozone-depleting cleaning solvents. Previously, we reported the cytotoxic effects of 2-BP on oocyte maturation and subsequent pre- and post-implantation development, both in vitro and in vivo . In the current study, we further demonstrate that these hazardous effects are suppressed by resveratrol, a grape-derived phytoalexin with known antioxidant and anti-inflammatory properties. Specifically, 2-BP treatment induced a significant reduction in the rates of oocyte maturation, fertilization, and in vitro embryonic development. Treatment of oocytes with 2-BP during in vitro maturation (IVM) resulted in increased resorption of post-implantation embryos and decreased fetal weights. Experiments with a mouse model disclosed that consumption of drinking water containing 20 μM 2-BP led to decreased oocyte maturation in vivo and fertilization in vitro , as well as impairment of early embryonic development. Notably, pretreatment with resveratrol prevented 2-BP-induced disruption of oocyte maturation and sequent embryonic development, both in vitro and in vivo . Our results collectively indicate that resveratrol has the potential to prevent the hazardous effects of 2-BP on embryos derived from pretreated oocytes. Keywords: 2-Bromopropane, resveratrol, apoptosis, oocyte maturation, embryonic development

  • Resveratrol Protects against 2-Bromopropane-Induced Apoptosis and Disruption of Embryonic Development in Blastocysts
    MDPI AG, 2011
    Co-Authors: Wen-hsiung Chan
    Abstract:

    2-Bromopropane (2-BP) is used as an alternative to ozone-depleting cleaning solvents. Previously, we reported that 2-BP has cytotoxic effects on mouse blastocysts and is associated with defects in subsequent development. In the present work, we show that 2-BP induces apoptosis in the inner cell mass of mouse blastocysts, and inhibits cell proliferation. Both effects are suppressed by resveratrol, a grape-derived phytoalexin with known antioxidant and anti-inflammatory properties. 2-BP-treated blastocysts displayed lower levels of implantation (compared to controls) when plated on culture dishes in vitro, and a reduced ability to proceed to later stages of embryonic development. Pretreatment with resveratrol prevented 2-BP-induced disruption of embryonic development, both in vitro and in vivo. Further investigation of these processes revealed that 2-BP directly promotes ROS generation, loss of mitochondrial membrane potential (MMP), and activation of caspase-3, whereas resveratrol effectively blocks 2-BP-induced ROS production and the accompanying apoptotic biochemical changes. Our results collectively imply that 2-BP triggers the mitochondrion-dependent apoptotic pathway via ROS generation, and the antioxidant activity of resveratrol prevents 2-BP-induced toxicity

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