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Dose–response relationship of pulmonary disorders by inhalation exposure to cross-linked water-soluble acrylic acid polymers in F344 rats

BACKGROUND: In Japan, six workers handling cross-linked water-soluble acrylic acid polymer (CWAAP) at a chemical plant suffered from lung diseases, including fibrosis, interstitial pneumonia, emphysema, and pneumothorax. We recently demonstrated that inhalation of CWAAP-A, one type of CWAAP, causes...

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Autores principales: Takeda, Tomoki, Yamano, Shotaro, Goto, Yuko, Hirai, Shigeyuki, Furukawa, Yusuke, Kikuchi, Yoshinori, Misumi, Kyohei, Suzuki, Masaaki, Takanobu, Kenji, Senoh, Hideki, Saito, Misae, Kondo, Hitomi, Daghlian, George, Hong, Young-Kwon, Yoshimatsu, Yasuhiro, Hirashima, Masanori, Kobashi, Yoichiro, Okamoto, Kenzo, Kishimoto, Takumi, Umeda, Yumi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8994297/
https://www.ncbi.nlm.nih.gov/pubmed/35395797
http://dx.doi.org/10.1186/s12989-022-00468-9
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author Takeda, Tomoki
Yamano, Shotaro
Goto, Yuko
Hirai, Shigeyuki
Furukawa, Yusuke
Kikuchi, Yoshinori
Misumi, Kyohei
Suzuki, Masaaki
Takanobu, Kenji
Senoh, Hideki
Saito, Misae
Kondo, Hitomi
Daghlian, George
Hong, Young-Kwon
Yoshimatsu, Yasuhiro
Hirashima, Masanori
Kobashi, Yoichiro
Okamoto, Kenzo
Kishimoto, Takumi
Umeda, Yumi
author_facet Takeda, Tomoki
Yamano, Shotaro
Goto, Yuko
Hirai, Shigeyuki
Furukawa, Yusuke
Kikuchi, Yoshinori
Misumi, Kyohei
Suzuki, Masaaki
Takanobu, Kenji
Senoh, Hideki
Saito, Misae
Kondo, Hitomi
Daghlian, George
Hong, Young-Kwon
Yoshimatsu, Yasuhiro
Hirashima, Masanori
Kobashi, Yoichiro
Okamoto, Kenzo
Kishimoto, Takumi
Umeda, Yumi
author_sort Takeda, Tomoki
collection PubMed
description BACKGROUND: In Japan, six workers handling cross-linked water-soluble acrylic acid polymer (CWAAP) at a chemical plant suffered from lung diseases, including fibrosis, interstitial pneumonia, emphysema, and pneumothorax. We recently demonstrated that inhalation of CWAAP-A, one type of CWAAP, causes pulmonary disorders in rats. It is important to investigate dose–response relationships and recoverability from exposure to CWAAPs for establishing occupational health guidelines, such as setting threshold limit value for CWAAPs in the workplace. METHODS: Male and female F344 rats were exposed to 0.3, 1, 3, or 10 mg/m(3) CWAAP-A for 6 h/day, 5 days/week for 13 weeks using a whole-body inhalation exposure system. At 1 h, 4 weeks, and 13 weeks after the last exposure the rats were euthanized and blood, bronchoalveolar lavage fluid, and all tissues including lungs and mediastinal lymph nodes were collected and subjected to biological and histopathological analyses. In a second experiment, male rats were pre-treated with clodronate liposome or polymorphonuclear leukocyte-neutralizing antibody to deplete macrophages or neutrophils, respectively, and exposed to CWAAP-A for 6 h/day for 2 days. RESULTS: CWAAP-A exposure damaged only the alveoli. The lowest observed adverse effect concentration (LOAEC) was 1 mg/m(3) and the no observed adverse effect concentration (NOAEC) was 0.3 mg/m(3). Rats of both sexes were able to recover from the tissue damage caused by 13 weeks exposure to 1 mg/m(3) CWAAP-A. In contrast, tissue damage caused by exposure to 3 and 10 mg/m(3) was irreversible due to the development of interstitial lung lesions. There was a gender difference in the recovery from CWAAP-A induced pulmonary disorders, with females recovering less than males. Finally, acute lung effects caused by CWAAP-A were significantly reduced by depletion of alveolar macrophages. CONCLUSIONS: Pulmonary damage caused by inhalation exposure to CWAAP-A was dose-dependent, specific to the lung and lymph nodes, and acute lung damage was ameliorated by depleting macrophages in the lungs. CWAAP-A had both a LOAEC and a NOAEC, and tissue damage caused by exposure to 1 mg/m(3) CWAAP-A was reversible: recovery in female rats was less than for males. These findings indicate that concentration limits for CWAAPs in the workplace can be determined. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12989-022-00468-9.
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spelling pubmed-89942972022-04-10 Dose–response relationship of pulmonary disorders by inhalation exposure to cross-linked water-soluble acrylic acid polymers in F344 rats Takeda, Tomoki Yamano, Shotaro Goto, Yuko Hirai, Shigeyuki Furukawa, Yusuke Kikuchi, Yoshinori Misumi, Kyohei Suzuki, Masaaki Takanobu, Kenji Senoh, Hideki Saito, Misae Kondo, Hitomi Daghlian, George Hong, Young-Kwon Yoshimatsu, Yasuhiro Hirashima, Masanori Kobashi, Yoichiro Okamoto, Kenzo Kishimoto, Takumi Umeda, Yumi Part Fibre Toxicol Research BACKGROUND: In Japan, six workers handling cross-linked water-soluble acrylic acid polymer (CWAAP) at a chemical plant suffered from lung diseases, including fibrosis, interstitial pneumonia, emphysema, and pneumothorax. We recently demonstrated that inhalation of CWAAP-A, one type of CWAAP, causes pulmonary disorders in rats. It is important to investigate dose–response relationships and recoverability from exposure to CWAAPs for establishing occupational health guidelines, such as setting threshold limit value for CWAAPs in the workplace. METHODS: Male and female F344 rats were exposed to 0.3, 1, 3, or 10 mg/m(3) CWAAP-A for 6 h/day, 5 days/week for 13 weeks using a whole-body inhalation exposure system. At 1 h, 4 weeks, and 13 weeks after the last exposure the rats were euthanized and blood, bronchoalveolar lavage fluid, and all tissues including lungs and mediastinal lymph nodes were collected and subjected to biological and histopathological analyses. In a second experiment, male rats were pre-treated with clodronate liposome or polymorphonuclear leukocyte-neutralizing antibody to deplete macrophages or neutrophils, respectively, and exposed to CWAAP-A for 6 h/day for 2 days. RESULTS: CWAAP-A exposure damaged only the alveoli. The lowest observed adverse effect concentration (LOAEC) was 1 mg/m(3) and the no observed adverse effect concentration (NOAEC) was 0.3 mg/m(3). Rats of both sexes were able to recover from the tissue damage caused by 13 weeks exposure to 1 mg/m(3) CWAAP-A. In contrast, tissue damage caused by exposure to 3 and 10 mg/m(3) was irreversible due to the development of interstitial lung lesions. There was a gender difference in the recovery from CWAAP-A induced pulmonary disorders, with females recovering less than males. Finally, acute lung effects caused by CWAAP-A were significantly reduced by depletion of alveolar macrophages. CONCLUSIONS: Pulmonary damage caused by inhalation exposure to CWAAP-A was dose-dependent, specific to the lung and lymph nodes, and acute lung damage was ameliorated by depleting macrophages in the lungs. CWAAP-A had both a LOAEC and a NOAEC, and tissue damage caused by exposure to 1 mg/m(3) CWAAP-A was reversible: recovery in female rats was less than for males. These findings indicate that concentration limits for CWAAPs in the workplace can be determined. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12989-022-00468-9. BioMed Central 2022-04-08 /pmc/articles/PMC8994297/ /pubmed/35395797 http://dx.doi.org/10.1186/s12989-022-00468-9 Text en © The Author(s) 2022, corrected publication 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Takeda, Tomoki
Yamano, Shotaro
Goto, Yuko
Hirai, Shigeyuki
Furukawa, Yusuke
Kikuchi, Yoshinori
Misumi, Kyohei
Suzuki, Masaaki
Takanobu, Kenji
Senoh, Hideki
Saito, Misae
Kondo, Hitomi
Daghlian, George
Hong, Young-Kwon
Yoshimatsu, Yasuhiro
Hirashima, Masanori
Kobashi, Yoichiro
Okamoto, Kenzo
Kishimoto, Takumi
Umeda, Yumi
Dose–response relationship of pulmonary disorders by inhalation exposure to cross-linked water-soluble acrylic acid polymers in F344 rats
title Dose–response relationship of pulmonary disorders by inhalation exposure to cross-linked water-soluble acrylic acid polymers in F344 rats
title_full Dose–response relationship of pulmonary disorders by inhalation exposure to cross-linked water-soluble acrylic acid polymers in F344 rats
title_fullStr Dose–response relationship of pulmonary disorders by inhalation exposure to cross-linked water-soluble acrylic acid polymers in F344 rats
title_full_unstemmed Dose–response relationship of pulmonary disorders by inhalation exposure to cross-linked water-soluble acrylic acid polymers in F344 rats
title_short Dose–response relationship of pulmonary disorders by inhalation exposure to cross-linked water-soluble acrylic acid polymers in F344 rats
title_sort dose–response relationship of pulmonary disorders by inhalation exposure to cross-linked water-soluble acrylic acid polymers in f344 rats
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8994297/
https://www.ncbi.nlm.nih.gov/pubmed/35395797
http://dx.doi.org/10.1186/s12989-022-00468-9
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