Mutsuko Hirata-Koizumi

National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, Japan

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Publications (62)114.23 Total impact

  • A. Ono · M. Matsumoto · M. Takahashi · T. Kawamura · M. Hirata-Koizumi · A. Hirose ·

    Toxicology Letters 10/2015; 238(2):S340. DOI:10.1016/j.toxlet.2015.08.969 · 3.26 Impact Factor

  • Toxicology Letters 10/2015; 238(2):S136. DOI:10.1016/j.toxlet.2015.08.426 · 3.26 Impact Factor
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    Mutsuko Hirata-Koizumi · Sakiko Fujii · Kato Hina · Mariko Matsumoto · Mika Takahashi · Atsushi Ono · Akihiko Hirose ·
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    ABSTRACT: Perfluoroalkyl carboxylic acids (PFCAs) are global environmental contaminants that are the cause of concern due to their possible effects on wildlife and human health. Since few studies have investigated the toxicity of long-chain PFCAs, we have performed combined repeated dose toxicity studies with the reproduction/developmental toxicity screening tests. We previously examined perfluoroundecanoic acid (C11), perfluorododecanoic acid (C12), and perfluorooctadecanoic acid (C18). We herein reported our results for perfluorotetradecanoic acid (PFTeDA; C14) and perfluorohexadecanoic acid (PFHxDA: C16). Male and female rats were administered PFTeDA at 1, 3 or 10 mg/kg/day or PFHxDA at 4, 20 or 100 mg/kg/day by gavage, and each female was then mated with a male in the same dose group after 14 days. Males were dosed for a total of 42 days and females were dosed throughout the gestation period until day 5 after parturition. PFTeDA and PFHxDA caused hepatocyte hypertrophy and/or fatty changes in the liver at the middle and high doses. PFTeDA also induced follicular cell hypertrophy in the thyroid at the middle and high doses. The only reproductive/developmental effect observed was an inhibited postnatal body weight gain in pups in the 10 mg/kg/day PFTeDA group. Based on these results, the NOAELs for the repeated dose and reproductive/developmental toxicity were concluded to be 1 and 3 mg/kg/day for PFTeDA and 4 and 100 mg/kg/day for PFHxDA, respectively. Our current and previous results indicate that the toxicity of PFCAs decreases with increases in the carbon chain length from 12 to 18.
    01/2015; 2(4):177-190. DOI:10.2131/fts.2.177

  • 01/2015; 2(4):191-200. DOI:10.2131/fts.2.191
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    ABSTRACT: Hydroquinone (HQ) is used in skin bleaching agents, hair dyes, and finger nail treatments. Many skin-lightening cosmetics that contain HQ are currently marketed in Japan. Concerns have been expressed regarding health risks to the general population because the carcinogenicity of HQ was previously suggested in animal studies. HQ induced hepatocellular adenomas and forestomach hyperplasias in mice and renal tubular cell adenomas in male rats. In the present study, the lacZ transgenic mutation assay was conducted according to OECD test guideline 488 to determine whether mutagenic mechanisms were involved in HQ-induced carcinogenesis. Male Muta™ mice were repeatedly administered HQ orally at dosages of 0, 25, 50, 100, or 200 mg/kg bw/day for 28 days. Body weight gain was decreased in all treatment groups. No significant differences were observed in mutant frequencies in the liver, stomach, lung, or kidney between HQ-treated mice and the concurrent negative controls, whereas the significant induction of mutations was noted in the positive control, N-ethyl-N-nitrosourea. These results suggest that a mutagenic mechanism is not responsible for HQ-induced carcinogenesis.
    Mutation Research/Genetic Toxicology and Environmental Mutagenesis 10/2014; 775-776. DOI:10.1016/j.mrgentox.2014.10.009 · 2.42 Impact Factor
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    Toxicology Letters 09/2014; 229. DOI:10.1016/j.toxlet.2014.06.786 · 3.26 Impact Factor
  • Mutsuko Hirata-Koizumi · Sakiko Fujii · Masatoshi Furukawa · Atsushi Ono · Akihiko Hirose ·
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    ABSTRACT: Male and female rats were given perfluorooctadecanoic acid (PFOdA) by gavage at 40, 200 or 1,000 mg/kg/day, and each female was mated with a male in the same dose group after 14-day administration. Males were dosed for 42 days and females were dosed throughout the gestation period until day 5 of lactation. One female given 1,000 mg/kg/day was euthanized on day 18 of gestation due to a moribund condition; however, no other treatment-related clinical signs of toxicity were observed. Body weights fell at 1,000 mg/kg/day from day 28 through the administration period in males and throughout gestation and lactation in females. Red blood cell count, hemoglobin level and hematocrit were decreased at 200 and 1,000 mg/kg/day in males and activated partial thromboplastin time was prolonged at 1,000 mg/kg/ day in females. Histopathological examination revealed hepatic changes, such as centrilobular hypertrophy and necrosis, in males given 200 and 1,000 mg/kg/day and in females given 1,000 mg/kg/day. Pancreatic zymogen granule was decreased in both sexes at 1,000 mg/kg/day. As for reproductive and developmental toxicity, there were decreases in the number of corpora lutea, implantation, total number of pups born and the number of live pups on postnatal days 0 and 4 at 1,000 mg/kg/day. At this dose, birth weights of pups were decreased and postnatal body weight gain was inhibited. Based on these findings, the NOAEL of PFOdA was considered to be 40 mg/kg/day for repeated dose toxicity and 200 mg/kg/day for reproductive/developmental toxicity.
    The Journal of Toxicological Sciences 04/2014; 37(1):63-79. DOI:10.1002/tox.21996 · 1.29 Impact Factor
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    ABSTRACT: Historical control data on rodent developmental toxicity studies, performed between 1994 and 2010, were obtained from 19 laboratories in Japan, including 10 pharmaceutical and chemical companies and 9 contract research organizations. Rats, mice, and hamsters were used for developmental toxicity studies. Data included maternal reproductive findings at terminal cesarean sections and fetal findings including the spontaneous incidences of external, visceral, and skeletal anomalies. No noticeable differences were observed in maternal reproductive data between laboratories. Inter-laboratory variations in the incidences of fetuses with anomalies appeared to be due to differences in the selection of observation parameters, observation criteria, classification of the findings, and terminology of fetal alterations. Historical control data are useful for the appropriate interpretation of experimental results and evaluation of the effects of chemical on reproductive and developmental toxicities.
    Congenital Anomalies 01/2014; 54(3). DOI:10.1111/cga.12050 · 1.08 Impact Factor
  • Atsushi Ono · Mutsuko Hirata-Koizumi · Ryota Ise · Hirohito Kato · Takashi Matsuyama · Makoto Ema · Akihiko Hirose ·

    Toxicology Letters 08/2013; 221:S206. DOI:10.1016/j.toxlet.2013.05.486 · 3.26 Impact Factor
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    ABSTRACT: A 28-day repeated dose toxicity test and reproduction/developmental toxicity test for N,N'-diphenyl-p-phenylenediamine (DPPD) were conducted in [Crl:CD(SD)] SPF rats. Male and female rats were dosed with DPPD by gavage for 28days at 0, 100, 300, or 1000mg/kg bw/day or for a total of 42-46days at 0, 8, 50, or 300mg/kg bw/day. No significant adverse effects were observed in the repeated dose toxicity study up to 1000mg/kg bw/day in both sexes. In the reproduction/developmental toxicity study, two females showed piloerection, hypothermia, and pale skin; one died and the other showed dystocia on day 23 of pregnancy at 300mg/kg bw/day. Another female delivered only three live pups at 300mg/kg bw/day. A significantly prolonged gestation period was observed at 50 and 300mg/kg bw/day. The NOAELs of repeated dose toxicity and reproduction/developmental toxicity were considered to be 1000 and 8mg/kg bw/day, respectively.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 02/2013; 56. DOI:10.1016/j.fct.2013.02.029 · 2.90 Impact Factor
  • Mutsuko Hirata-Koizumi · Mika Takahashi · Mariko Matsumoto · Tomoko Kawamura · Atsushi Ono · Akihiko Hirose ·
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    ABSTRACT: Phthalate esters are widely used as plasticizers in polyvinyl chloride products. Because of human health concerns, regulatory authorities in Japan, US, Europe and other countries control the use of di(2-ethylhexyl) phthalate, diisononyl phthalate, di-n-butyl phthalate, butylbenzyl phthalate, diisodecyl phthalate and di-n-octyl phthalate for the toys that can be put directly in infants' mouths. While these regulatory actions will likely reduce the usage of phthalate esters, there is concern that other plasticizers that have not been sufficiently evaluated for safety will be used more frequently. We therefore collected and evaluated the toxicological information on di(2-ethylhexyl) terephthalate (DEHT), 1,2-cyclohexanedicarboxylic acid, diisononyl ester (DINCH), diisononyl adipate (DINA), 2,2,4-trimetyl-1,3-pentanediol diisobutyrate (TXIB), tri-n-butyl citrate (TBC) and acetyl tri-n-butyl citrate (ATBC) which were detected at a relatively high frequency in toys. The collected data have shown that chronic exposure to DEHT affects the eye and nasal turbinate, and DINCH exerts effects on the thyroid and kidney in rats. DINA and TXIB have been reported to have hepatic and renal effects in dogs or rats, and ATBC slightly affected the liver in rats. The NOAELs for repeated dose toxicity are relatively low for DINCH (40 mg/kg bw/day) and TXIB (30 mg/kg bw/day) compared with DEHT, DINA and ATBC. DEHT, TXIB and ATBC have been reported to have reproductive/developmental effects at relatively high doses in rats. For DINA and TBC, available data are insufficient for assessing the hazards, and therefore, adequate toxicity studies should be conducted. In the present review, the toxicity information on 6 alternatives to phthalate plasticizers is summarized, focusing on the effects after oral exposure, which is the route of most concern.
    Kokuritsu Iyakuhin Shokuhin Eisei Kenkyūjo hōkoku = Bulletin of National Institute of Health Sciences 12/2012; 130(130):31-42.
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    ABSTRACT: Crl:CD(SD)rats were given 3-cyanopyridine by gavage at 0, 5, 30 or 180 mg/kg/day. Males were dosed for 42 days beginning 14 days before mating, and females for 40-53 days beginning 14 days before mating to day 3 of lactation, including throughout the mating and gestation periods. General toxicity, mainly liver damage, was observed in males at >= 30 mg/kg/day and in females at >= 5 mg/kg/day. Sertoli cell vacuolation was observed at 180 mg/kg/day, and spermatocyte damages were observed at >= 30 mg/kg/day. Effects on estrous cycles, corpora lutea and implantations, and unsuccessfully mated females, despite additional mating, were observed at 180 mg/kg/day. Delayed initiation of delivery, dystocia, and deaths or mori-bundities of pregnant females were observed at 180 mg/kg/day, and only two pregnant rats delivered live pups at that dose. The NOAEL for reproductive/developmental toxicity was concluded to be 30 mg/kg/day.
    Reproductive Toxicology 11/2012; 35(1). DOI:10.1016/j.reprotox.2012.10.014 · 3.23 Impact Factor
  • Ryuichi Hasegawa · Mutsuko Hirata-Koizumi · Michael L Dourson · Ann Parker · Atsushi Ono · Akihiko Hirose ·
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    ABSTRACT: The available toxicity information for boron was reevaluated and four appropriate toxicity studies were selected in order to derive a tolerable daily intake (TDI) using newly proposed uncertainty factors (UFs) presented in Hasegawa et al. (2010). No observed adverse effect levels (NOAELs) of 17.5 and 8.8 mg B/kg/day for the critical effect of testicular toxicity were found in 2-year rat and dog feeding studies. Also, the 95% lower confidence limit of the benchmark doses for 5% reduction of fetal body weight (BMDL(05)) was calculated as 44.9 and 10.3 mg B/kg/day in mouse and rat developmental toxicity studies, respectively. Measured values available for differences in boron clearance between rats and humans and variability in the glomerular filtration rate (GFR) in pregnant women were used to derive chemical specific UFs. For the remaining uncertainty, newly proposed default UFs, which were derived from the latest applicable information with a probabilistic approach, and their subdivided factors for toxicokinetic and toxicodynamic variability were applied. Finally, overall UFs were calculated as 68 for rat testicular toxicity, 40 for dog testicular toxicity, 250 for mouse developmental toxicity and 78 for rat developmental toxicity. It is concluded that 0.13 mg B/kg/day is the most appropriate TDI for boron, based on rat developmental toxicity.
    Regulatory Toxicology and Pharmacology 11/2012; 65(1). DOI:10.1016/j.yrtph.2012.10.013 · 2.03 Impact Factor
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    ABSTRACT: Three female Crl:CD(SD) rats/group were dosed with single wall carbon nanotube (SWCNT) or multi wall carbon nanotube (MWCNT) four times by gavage at a total of 50 mg/kg bw or 200 mg/kg bw (four equally divided doses at one-hour intervals). Acute oral doses of SWCNT and MWCNT caused neither death nor toxicological effects, and thus the oral LD 50 values for SWCNT and MWCNT were considered to be greater than 50 mg/kg bw and 200 mg/kg bw, in rats respectively. Five or ten Crl:CD(SD) rats/sex were dosed with SWCNT once daily by gavage at a dose of 0 (control), 0.125, 1.25 or 12.5 mg/kg bw/day for 28 days with a 14-day recovery period (0 and 12.5 mg/kg bw/day groups). Six or twelve Crl:CD(SD) rats/sex were dosed with MWCNT once daily by gavage at a dose of 0 (control), 0.5, 5.0 or 50 mg/kg bw/day for 28 days with a 14-day recovery period (0 and 50 mg/kg bw/day groups). Based on no toxicological effects, the no observed adverse effect levels (NOAELs) of repeated dose toxicity of SWCNT and MWCNT were considered to be 12.5 mg/kg bw/day and 50 mg/kg bw/day (the highest dose tested), respectively. It was suggested that SWCNT and MWCNT dosed by gavage reached the gastro-intestinal tract as agglomerates and were mostly excreted via feces.
    The Journal of Toxicological Sciences 06/2012; 37(3):463-74. DOI:10.2131/jts.37.463 · 1.29 Impact Factor

  • Toxicology Letters 06/2012; 211:S184-S185. DOI:10.1016/j.toxlet.2012.03.665 · 3.26 Impact Factor
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    ABSTRACT: To obtain initial information on the possible repeated-dose oral toxicity of fullerene C60, Crl:CD(SD) rats were administered fullerene C60 by gavage once daily at 0 (vehicle: corn oil), 1, 10, 100, or 1,000 mg/kg/day for 29 days, followed by a 14-day recovery period. No deaths occurred in any groups, and there were no changes from controls in detailed clinical observations, body weights, and food consumption in any treatment groups. Moreover, no treatment-related histopathological changes were found in any organs examined at the end of the administration period and at the end of the recovery period. Blackish feces and black contents of the stomach and large intestine were observed in males and females at 1,000 mg/kg/day in the treatment group. There were no changes from controls in the liver and spleen weights at the end of the administration period, but those weights in males in the 1,000 mg/kg/day group increased at the end of the recovery period. Using liquid chromatography-tandem mass spectrometry, fullerene C60 were not detected in the liver, spleen or kidney at the end of the administration period and also at the end of the recovery period. In conclusion, the present study revealed no toxicological effects of fullerene C60; however, the slight increases in liver and spleen weights after the 14-day recovery period may be because of the influence of fullerene C60 oral administration. In the future, it will be necessary to conduct a long-term examination because the effects of fullerene C60 cannot be ruled out.
    The Journal of Toxicological Sciences 04/2012; 37(2):353-61. DOI:10.2131/jts.37.353 · 1.29 Impact Factor
  • A. Ono · M. Takahashi · T. Kawamura · E. Kamata · M. Hirata-Koizumi · A. Hirose ·

    Fuel and Energy Abstracts 08/2011; 205. DOI:10.1016/j.toxlet.2011.05.351
  • A. Hirose · A. Ono · M. Hirata-Koizumi · H. Serizawa · M. Sunaga · M. Furukawa · E. Kamata · T. Nishimura ·

    Fuel and Energy Abstracts 08/2011; 205. DOI:10.1016/j.toxlet.2011.05.961
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    ABSTRACT: Aluminium ammonium sulfate (AAS) was tested for reproductive/developmental toxicity in a two-generation study. Male and female rats were continuously given AAS in drinking water at 0, 50, 500 or 5000 ppm. Water consumption was decreased in all AAS-treated groups, and the body weight of parental animals transiently decreased in the 5000 ppm group. In either generation, no compound-related changes were found in estrous cyclicity, sperm parameters, copulation, fertility and gestation index, number of implantations and live birth pups, sex ratios of pups or viability during the preweaning period. Male and female F1 pups in the 5000 ppm group showed a lower body weight on postnatal day 21, while there were no differences in the birth weight of F1 and F2 pups between the control and AAS-treated groups. Preweaning body weight gain in F2 males and females indicated a similar decreasing tendency at 5000 ppm. In F1 and F2 weanlings, the weight of the liver, spleen and thymus decreased at 5000 ppm, but no histopathological changes were found in these organs. In F1 females in the 5000 ppm group, vaginal opening was delayed slightly. There were no compound-related changes in male preputial separation or in other developmental landmarks. In behavioral tests conducted for F1 animals at 4-6 weeks of age, no compound-related changes were found in spontaneous locomotor activity and performance in a water-filled multiple T-maze. In conclusion, the NOAEL of AAS for two-generation reproductive/developmental toxicity was considered to be 500 ppm in rats. Considering the aluminium content in the basal diet, the total ingested dose of aluminium from drinking water and food in this 500 ppm group was calculated to be 5.35 mgAl/kgbw/day.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 05/2011; 49(9):1948-59. DOI:10.1016/j.fct.2011.04.035 · 2.90 Impact Factor
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    ABSTRACT: In a two-generation reproductive toxicity study, male and female rats were given aluminium sulfate (AS) in drinking water at 0, 120, 600 or 3000 ppm. AS reduced water consumption in all treatment groups, and body weight was transiently decreased in the 3000 ppm group. In the F1 and F2 pups, preweaning body weight gain was inhibited at 3000 ppm, and the liver and spleen weight was decreased at weaning. At this dose, vaginal opening was slightly delayed. There were no compound-related changes in other reproductive/developmental parameters, including developmental neurobehavioral endpoints. The data indicated that the NOAEL of AS in this two-generation study is 600 ppm for parental systemic toxicity and reproductive/developmental toxicity. The total ingested dose of aluminium from drinking water and food (standard rat diet, containing 25-29 ppm of aluminium) combined for this 600 ppm group was calculated to be 8.06 mg Al/kg bw/day.
    Reproductive Toxicology 11/2010; 31(2):219-30. DOI:10.1016/j.reprotox.2010.11.004 · 3.23 Impact Factor

Publication Stats

504 Citations
114.23 Total Impact Points


  • 2014
    • National Institute of Advanced Industrial Science and Technology
      Tsukuba, Ibaraki, Japan
  • 2005-2014
    • National Institute of Health Sciences, Japan
      • • Division of Pathology at Biological Safety Research Center
      • • Division of Risk Assessment
      • • Division of Medicinal Safety Science
      Edo, Tokyo, Japan
  • 2013
    • Shin Nippon Biomedical Laboratories, Ltd.
      Kagosima, Kagoshima, Japan
  • 2008
    • National Institute of Occupational Safety and Health JAPAN
      Edo, Tōkyō, Japan