Technology to reduce transfer, accumulation, and toxic effects on organisms and humans without reducing heavy metal concentrations in contaminated soil

• Project/Area Number: 23K28235
• Project/Area Number (Other): 23H03545 (2023)
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Multi-year Fund (2024); Single-year Grants (2023)
• Section: 一般
• Review Section: Basic Section 63030:Chemical substance influence on environment-related
• Research Institution: Hokkaido University
• Principal Investigator: 中山 翔太 北海道大学, 獣医学研究院, 准教授 (90647629)
• Co-Investigator(Kenkyū-buntansha): 伊藤 真由美 北海道大学, 工学研究院, 教授 (10339690) ; 山崎 淳平 北海道大学, 獣医学研究院, 准教授 (20732902) ; 江口 哲史 千葉大学, 予防医学センター, 講師 (70595826) ; 内田 義崇 北海道大学, 農学研究院, 准教授 (70705251)
• Project Period (FY): 2023-04-01 – 2026-03-31
• Project Status: Granted (Fiscal Year 2024)
• Budget Amount: ¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000); Fiscal Year 2025: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2024: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2023: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
• Keywords: 金属汚染 / 低減技術 / メタボローム解析 / エピジェネティクス解析

Outline of Research at the Start

本研究では、「土壌や粉塵の鉛形態を人為的に改善操作することで、土壌や粉塵の鉛濃度は低下させなくても、生物に吸収される鉛量を低減可能であり、鉛曝露レベルや曝露による毒性影響を低減できるのでは無いか？」と作業仮説を立て、土壌中の微生物コミュニティ多様化や鉛の化学形態を変化させる新規手法の開発と生物における鉛の体内動態、鉛蓄積による血液毒性、臓器毒性、各種ホルモン変動、遺伝制御に関わるゲノミクスやエピジェネティクス、種々の疾患の引き金となり得る腸内細菌叢プロファイルの攪乱など多面的に毒性影響を評価し、生物の毒性影響の低減を成し遂げる

Outline of Annual Research Achievements

本研究では「土壌や粉塵の鉛形態を農学・工学的に改善し、土壌や粉塵の鉛濃度は低下させずに、生物に吸収される鉛量を低減させ、鉛（Pb）曝露レベルや曝露による毒性影響を低減可能では無いか？」と仮説を立て、マウスを用いたIn Vivo試験を実施した。汚染土壌由来の曝露を模擬し、C57/BL6マウス（1群6匹）をPbを添加した土壌および、さらに改良剤で処理した土壌の上で3ヶ月間飼育曝露した。塩基性炭酸鉛（2PbCO3-Pb(OH)2）、硫酸鉛（PbSO4）、硫化鉛（PbS）をPb源として用い、土壌中の濃度は3000mg Pb/kgとした。農学的手法として鶏糞を用い、工学的手法としてリン酸（PA）、三重過リン酸塩（TSP）、ドロマイトをPbを添加した土壌の改良剤として使用し、添加の有無によるマウスにおける鉛の血液中、臓器中の濃度を比較した。鶏糞を用いた場合、30日目の脳、腎臓、肺のPb濃度は、それぞれ28.58、26.63、25.62％の減少率で有意差を示した。肺と気管を除く脳、腎臓、肝臓、骨も98日目に同様の減少を示し、減少率はそれぞれ11.82、4.63、29.87、14.54％であった。脳におけるNrf2、HMOX1、SOD1、CAT、BCL2、Baxのレベルには、曝露98日後で改良剤処理群の間で有意差が見られ、濃度低下に伴う毒性学的な影響の低減効果が考えられる。PA、TSPを用いた実験では、脳（40-80％）、肝臓（40-70％）、腎臓（30-40％）における蓄積する鉛濃度の低減効果が認められた。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

予定通り土壌改良剤を用いたIn Vivo試験を実施し、期待していた成果をあげることができている。2年度目に予定している実験もスケジュール通りに進められる準備が整っている。

Strategy for Future Research Activity

土壌改良剤を用いて実施したマウスのIn Vivo試験において、引き続き毒性学的な影響評価を実施する。ザンビアにおいてはイヌを対象とした実証試験を予定通り進めていく。

Research Products

• [Int'l Joint Research] ザンビア大学/ザンビア保健省/ザンビア鉱山省(ザンビア)
• [Journal Article] Current situation of lead (Pb) exposure in raptors and waterfowl in Japan and difference in sensitivity to in vitro lead exposure among avian species (2024)
  • Author(s): Maruyama Mizuki、Ushine Nana、Watanabe Yukiko、Ishii Chihiro、Saito Keisuke、Sakai Hidefumi、Kuritani Takeshi、Doya Rio、Ogasawara Kohei、Ikenaka Yoshinori、Yohannes Yared Beyene、Ishizuka Mayumi、Nakayama Shouta M.M.
  • Journal Title: Environmental Pollution Volume: 349 Pages: 123907-123907
  • DOI: 10.1016/j.envpol.2024.123907
  • Peer Reviewed / Open Access
• [Journal Article] Effect of chicken manure amendment on lead burden in mice: exposure to lead-spiked soil (2024)
  • Author(s): Soe Nyein Chan、Yohannes Yared Beyene、Ohigashi Takamitsu、Nakata Hokuto、Tatsumi Chikae、Uchida Yoshitaka、Mufalo Walubita、Ito Mayumi、Sato Tsutomu、Igarashi Toshifumi、Ikenaka Yoshinori、Ishizuka Mayumi、Nakayama Shouta M. M.
  • Journal Title: Journal of Soils and Sediments Volume: in press Issue: 5 Pages: 2001-2011
  • DOI: 10.1007/s11368-024-03769-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Insights on hazardous metal bioaccessibility, and groundwater impacted by Zn residues from a legacy mine and risk evaluation of adjacent soils (2024)
  • Author(s): Mufalo Walubita、Arima Takahiko、Igarashi Toshifumi、Ito Mayumi、Sato Tsutomu、Tomiyama Shingo、Nyambe Imasiku、Tabelin Carlito Baltazar、Nakata Hokuto、Nakayama Shouta、Ishizuka Mayumi
  • Journal Title: Environmental Geochemistry and Health Volume: 46 Issue: 2
  • DOI: 10.1007/s10653-024-01864-0
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Lead speciation in body tissues, gastrointestinal contents, and feces of lead-exposed wild rats (Rattus rattus) (2024)
  • Author(s): Fujimori Takashi、Toyomaki Haruya、Shiota Kenji、Nakata Hokuto、Yabe John、Muzandu Kaampwe、Chawinga Kenneth、Doya Rio、Soe Nyein Chan、Ishizuka Mayumi、Nakayama Shouta M.M.
  • Journal Title: Science of The Total Environment Volume: 908 Pages: 168297-168297
  • DOI: 10.1016/j.scitotenv.2023.168297
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Metals and arsenic distribution in stray dogs’ tissues around a lead-zinc mine in Kabwe, Zambia (2023)
  • Author(s): Nyein Chan Soe, Yared Beyene Yohannes, Andrew Kataba, Madalitso Tembo, John Yabe, Golden Zyambo, Kenneth Chawinga, Kaampwe Muzandu, Yoshinori Ikenaka, Mayumi Ishizuka, Shouta MM Nakayama
  • Journal Title: Environmental Science and Pollution Research Volume: 31 Issue: 8 Pages: 12083-12093
  • DOI: 10.1007/s11356-024-31948-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Evaluation of the Effect of Pb Pollution on Avian Influenza Virus-Specific Antibody Production in Black-Headed Gulls (Chroicocephalus ridibundus) (2023)
  • Author(s): Nana Ushine, Makoto Ozawa, Shouta M. M. Nakayama, Mayumi Ishizuka, Takuya Kato, Shin-ichi Hayama
  • Journal Title: Animals Volume: 13 Issue: 14 Pages: 2338-2338
  • DOI: 10.3390/ani13142338
  • Peer Reviewed / Open Access
• [Journal Article] Association between chronic environmental lead (Pb) exposure and cytokines in males and females of reproductive age from Kabwe, Zambia. (2023)
  • Author(s): Andrew Kataba, Yared Beyene Yohannes, Hokuto Nakata, John Yabe, Haruya Toyomaki, Kaampwe Muzandu, Golden Zyambo, Yoshinori Ikenaka, Kennedy Choongo, Mayumi Ishizuka, Shouta MM Nakayama
  • Journal Title: Int. J. Environ. Res. Public Health. Volume: 20 Issue: 8 Pages: 5596-5596
  • DOI: 10.3390/ijerph20085596
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] X-ray analytic microscopy with CT-guided sample extraction to analyze potential projectile fragments in a dead serow (2023)
  • Author(s): Kihara Yuko、Makino Yohsuke、Yokoyama Masaaki、Chiba Fumiko、Tanaka Aki、Nakayama Shouta M.M.、Hayama Shin-ichi、Ishizuka Mayumi、Nolte Kurt B.、Iwase Hirotaro
  • Journal Title: Legal Medicine Volume: 63 Pages: 102257-102257
  • DOI: 10.1016/j.legalmed.2023.102257
  • Peer Reviewed / Open Access
• [Journal Article] Immobilization of Pb and Zn leached from mining residue materials in Kabwe, Zambia: Performance of calcined dolomite in column experiments (2023)
  • Author(s): Mufalo Walubita、Tangviroon Pawit、Arima Takahiko、Igarashi Toshifumi、Ito Mayumi、Sato Tsutomu、Noto Kenta、Kawashima Takeshi、Nyambe Imasiku、Nakata Hokuto、Nakayama Shouta、Ishizuka Mayumi
  • Journal Title: Journal of Geochemical Exploration Volume: 249 Pages: 107209-107209
  • DOI: 10.1016/j.gexplo.2023.107209
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 日本における野鳥の鉛（Pb）汚染：鉛（Pb）汚染のモニタリングと毒性評価、及び今後の展望 (2023)
  • Author(s): 近藤充希、大沼学、中山翔太、鍋島 圭、大田和朋紀、石塚 真由美
  • Organizer: Japan Geoscience Union (JpGU) Meeting 2023～セッションM-ZZ41：環境汚染が進行する現代における環境、生物、人の調和を考える
  • Invited
• [Presentation] Land-Use Based Mapping of Lead Exposure Risk around a Former Mining Site in Zambia; using Lizard Biomonitoring Data. (2023)
  • Author(s): Rio Doya, Shouta M.M. Nakayama, Hokuto Nakata, John Yabe , Kaampwe Muzandu, Yoshinori Ikenaka , Mayumi Ishizuka
  • Organizer: Japan Geoscience Union (JpGU) Meeting 2023～セッションM-ZZ41：環境汚染が進行する現代における環境、生物、人の調和を考える
  • Invited
• [Presentation] 日本の野生猛禽類及びガン・カモ類における鉛汚染の実態と鉛同位体比を用いた曝露源の解明 (2023)
  • Author(s): 丸山瑞貴、銅谷理緒、牛根奈々、小笠原浩平、渡辺有希子、齊藤慶輔、栗谷豪、中川光弘、池中良徳、石塚真由美、中山翔太
  • Organizer: 第２回環境化学物質3学会合同大会
• [Presentation] アフリカにおける金属汚染：ザンビアの鉛汚染を例に (2023)
  • Author(s): 中山翔太、石塚真由美
  • Organizer: 第50回日本毒性学会学術年会：シンポジウム「途上国で「今」起こっている環境汚染とその毒性影響」
  • Invited
• [Presentation] Lead Exposure in Namibia: A Comparative Analysis Among Captive Cheetahs (Acinonyx jubatus), Wild Cheetahs, and Wild Leopards (Panthera pardus) (2023)
  • Author(s): Catherine Hauw, Anne Schmidt Kuntzel, John Yabe, Maria Diez-Leon, Niall McCann, Gerhard Iiputa, Mark Jago, Esther Mukete-Hilundutah, Trevor Nzehengwa, Nelly Banda, Shouta M.M. Nakayama, Mayumi Ishizuka, Matti Nghikembua, Becky Johnston, Jacqueline Ehrlich, Laurie Marker
  • Organizer: WRC2023
  • Int'l Joint Research / Invited
• [Presentation] オナガガモにおける鉛汚染およびインフルエンザ抗体量の免疫との関連性 (2023)
  • Author(s): 森口紗千子、牛根奈々、若山絵夢、加藤卓也、嶋田哲郎、杉野目斉、足利直哉、中山翔太、石塚真由美、羽賀淳、大沼学、山口剛士、田中良和、羽山伸一
  • Organizer: 日本鳥学会2023年度大会
• [Presentation] 国内の猛禽類及びガンカモ類における2022年以降の鉛汚染状況と曝露源の解明 (2023)
  • Author(s): 丸山瑞貴，銅谷理緒，牛根奈々，小笠原浩平，渡辺有希子，齊藤慶輔，栗谷豪，中川光弘，池中良徳，石塚真由美，中山翔太
  • Organizer: 日本鳥学会2023年度大会
• [Presentation] 北海道における近年の猛禽類の鉛中毒症発生状況 (2023)
  • Author(s): 渡辺有希子、河野晴子、石井千尋、丸山瑞貴、石塚真由美、中山翔太、齊藤慶輔
  • Organizer: 第29回日本野生動物医学会大会
• [Presentation] Health and development impacts of environmental lead contamination in children in the vicinity of a lead-zinc mine in Kabwe, Zambia (2023)
  • Author(s): Yabe J, Nakayama SMM, Nakata H, Munyinda NS, Toyomaki H, Yohannes YB, Muzandu K, Kataba A, Zyambo G, Mufune T, Liazambi A, Chawinga K, Choongo K, Ikenaka Y, Ishizuka M
  • Organizer: -International Symposium- Impact of Chemical and Biological Hazards on the Environment, Animals and Human Health and its Countermeasure
  • Int'l Joint Research / Invited
• [Presentation] Comparison of δ-aminolevulinic acid dehydratase (ALAD) sensitivity to in vitro lead exposure among avian species (2023)
  • Author(s): Mizuki Maruyama, Yukiko Watanabe, Chihiro Ishii, Keisuke Saito, Nana Ushine, Rio Doya, Kohei Ogasawara, Yoshinori Ikenaka, Yared Beyene Yohannes, Mayumi Ishizuka, Shouta M.M. Nakayama
  • Organizer: -International Symposium- Impact of Chemical and Biological Hazards on the Environment, Animals and Human Health and its Countermeasure
  • Int'l Joint Research
• [Presentation] Identifying lead exposure pattern in wild lizards and its relation with geographical features using lead isotopic ratio analysis (2023)
  • Author(s): Rio Doya, Shouta M.M. Nakayama, Hokuto Nakata, Haruya Toyomaki, John Yabe, Kaampwe Muzandu, Yared B. Yohannes Andrew Kataba Takeshi Kuritani Yoshinori Ikenaka, Mayumi Ishizuka
  • Organizer: -International Symposium- Impact of Chemical and Biological Hazards on the Environment, Animals and Human Health and its Countermeasure
  • Int'l Joint Research
• [Presentation] In vivo assessment of phosphate and liming amendments on lead contaminated soil (2023)
  • Author(s): Nyein Chan Soe, Mayumi Ito, Yoshinori Ikenaka, Mayumi Ishizuka, Shouta M.M. Nakayama
  • Organizer: -International Symposium- Impact of Chemical and Biological Hazards on the Environment, Animals and Human Health and its Countermeasure
  • Int'l Joint Research
• [Presentation] Sex Dependent Effects of Lead on Conception via Soil as Medium of Exposure in Mouse Model (2023)
  • Author(s): Banda Nelly, Soe Nyein Chan, Beyene Yared, Doya Rio, Ikenaka Yoshinori, Ishizuka Mayumi, Nakayama Shouta
  • Organizer: -International Symposium- Impact of Chemical and Biological Hazards on the Environment, Animals and Human Health and its Countermeasure
  • Int'l Joint Research
• [Presentation] Lead level in blood of Asian black bears in two different areas in central Japan (2023)
  • Author(s): Koji Yamazaki, Mayumi Ishizuka, Shouta MM Nakayama, Nelly Banda, Shinsuke Koike, Goto Yusuke, Kozo Yamazaki, Yui Nemoto, Boris Fuchs, Jon M. Arnemo
  • Organizer: 16th International Conference of Asian Society of Conservation Medicine
  • Int'l Joint Research
• [Presentation] Differences in blood δ-aminolevulinic acid dehydratase (ALAD) sensitivity to in vitro lead exposure among avian species（δ-アミノレブリン酸脱水酵素のin vitro鉛曝露に対する鳥類種間における感受性の違い） (2023)
  • Author(s): Mizuki Maruyama, Yukiko Watanabe, Chihiro Ishii, Keisuke Saito, Nana Ushine, Rio Doya, Kohei Ogasawara, Yoshinori Ikenaka, Yared Beyene Yohannes, Mayumi Ishizuka, Shouta M.M. Nakayama
  • Organizer: 7th International Chemical Hazard Symposiumおよび第7回環境化学討論会 北海道東北地区部会、中国四国地区部会合同シンポジウム
  • Int'l Joint Research
• [Presentation] Sex Dependent Effects of Lead on Conception via Soil as Medium of Exposure in Mouse Model (2023)
  • Author(s): Banda Nelly, Soe Nyein Chan, Beyene Yared, Doya Rio, Ikenaka Yoshinori, Ishizuka Mayumi, Nakayama Shouta
  • Organizer: 7th International Chemical Hazard Symposiumおよび第7回環境化学討論会 北海道東北地区部会、中国四国地区部会合同シンポジウム
  • Int'l Joint Research
• [Presentation] In vivo Evaluation of the Effects of Phosphate and Liming Amendments on Lead-Contaminated Soil (2023)
  • Author(s): Nyein Chan Soe, Mayumi Ito, Yoshinori Ikenaka, Mayumi Ishizuka, Shouta M.M. Nakayama
  • Organizer: 8th One Health Lecture Series: Enhance Scientific Collaboration for Healthier Society
  • Int'l Joint Research
• [Presentation] Variation in inhibitory effect of Pb on δ-aminolevulinic acid dehydratase (ALAD) among avians (2023)
  • Author(s): Mizuki Maruyama, Yukiko Watanabe, Chihiro Ishii, Keisuke Saito, Nana Ushine, Rio Doya, Kohei Ogasawara, Yoshinori Ikenaka, Yared Beyene Yohannes, Mayumi Ishizuka, Shouta M.M. Nakayama
  • Organizer: 8th One Health Lecture Series: Enhance Scientific Collaboration for Healthier Society
  • Int'l Joint Research
• [Remarks] 北海道大学大学院獣医学研究院毒性学教室
  • URL: http://tox.vetmed.hokudai.ac.jp/
• [Funded Workshop] -International Symposium- Impact of Chemical and Biological Hazards on the Environment, Animals and Human Health and its Countermeasure (2023)