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Food Chem Toxicol. 2014 Jul;69:267-75. doi: 10.1016/j.fct.2014.04.027. Epub 2014 Apr 22.

Polyhexamethyleneguanidine phosphate induces severe lung inflammation, fibrosis, and thymic atrophy.

Author information

1
Inhalation Toxicology Center, Jeonbuk Department of Non-human Primate, Korea Institute of Toxicology, Jeongeup-si, Jeollabukdo 580-185, Republic of Korea.
2
Toxicopathology Center, Non-human Primate Center, Jeonbuk Department of Non-human Primate, Korea Institute of Toxicology, Jeongeup-si, Jeollabukdo 580-185, Republic of Korea.
3
Analytical Center, Korea Institute of Toxicology, Daejeon 305-343, Republic of Korea.
4
Division of Toxicological Research, Korea Institute of Toxicology, Daejeon 305-343, Republic of Korea.
5
Inhalation Toxicology Center, Jeonbuk Department of Non-human Primate, Korea Institute of Toxicology, Jeongeup-si, Jeollabukdo 580-185, Republic of Korea. Electronic address: khlee@kitox.re.kr.

Abstract

Polyhexamethyleneguanidine phosphate (PHMG-P) has been widely used as a disinfectant because of its strong bactericidal activity and low toxicity. However, in 2011, the Korea Centers for Disease Control and Prevention and the Ministry of Health and Welfare reported that a suspicious outbreak of pulmonary disease might have originated from humidifier disinfectants. The purpose of this study was to assess the toxicity of PHMG-P following direct exposure to the lung. PHMG-P (0.3, 0.9, or 1.5 mg/kg) was instilled into the lungs of mice. The levels of proinflammatory markers and fibrotic markers were quantified in lung tissues and flow cytometry was used to evaluate T cell distribution in the thymus. Administration of PHMG-P induced proinflammatory cytokines elevation and infiltration of immune cells into the lungs. Histopathological analysis revealed a dose-dependent exacerbation of both inflammation and pulmonary fibrosis on day 14. PHMG-P also decreased the total cell number and the CD4(+)/CD8(+) cell ratio in the thymus, with the histopathological examination indicating severe reduction of cortex and medulla. The mRNA levels of biomarkers associated with T cell development also decreased markedly. These findings suggest that exposure of lung tissue to PHMG-P leads to pulmonary inflammation and fibrosis as well as thymic atrophy.

KEYWORDS:

Humidifier disinfectant; Lung fibrosis; Polyhexamethyleneguanidine phosphate; Pulmonary inflammation

PMID:
24769016
DOI:
10.1016/j.fct.2014.04.027
[Indexed for MEDLINE]

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