1.Development of a new alternative method to inhalation exposure: intratracheal instillation studies using molecular dispersion.
Toshiki MORIMOTO ; Chinatsu NISHIDA ; Hiroto IZUMI ; Taisuke TOMONAGA ; Kazuma SATO ; Yasuyuki HIGASHI ; Ke-Yong WANG ; Takuma KOJIMA ; Kazuo SAKURAI ; Akihiro MORIYAMA ; Jun-Ichi TAKESHITA ; Kei YAMASAKI ; Hidenori HIGASHI ; Kazuhiro YATERA ; Yasuo MORIMOTO
Environmental Health and Preventive Medicine 2025;30():69-69
BACKGROUND:
Organic chemicals have been known to cause allergic diseases such as bronchial asthma and hypersensitivity pneumonitis; however, the possibility that they do not cause irreversible pulmonary fibrosis has not been considered. Polyacrylic acid (PAA), an organic chemical, has caused irreversible progressive pulmonary fibrosis in exposed workers, indicating its potential to induce pulmonary inflammation and fibrosis. Although intratracheal instillation studies are commonly used for evaluating lung pathology, traditional methods face challenges with chemical substances, particularly nanoparticles, which tend to aggregate in suspension and prevent uniform pulmonary distribution. Such aggregation alters the qualitative and quantitative responses to lung injury, limiting accurate assessment of lung pathology. To overcome this limitation, we developed a 'molecular dispersion method' that uses pH modification to negative charges to PAA particles, maintaining their dispersion. Using this method, we investigated the effects of PAA on pulmonary inflammation and fibrosis in a rat model.
METHODS:
F344 rats were intratracheally instilled with PAA using molecular dispersion (0.1 mg/rat, 1.0 mg/rat), PAA without molecular dispersion (1.0 mg/rat), and normal saline (control group). Rats were sacrificed at 3 days, 1 week, 1 month, 3 months, and 6 months after exposure to examine inflammatory and fibrotic responses.
RESULTS:
PAA caused persistent increases in neutrophil influx in the bronchoalveolar lavage fluid (BALF) from 3 days to 1 month following instillation. In histopathological findings, the group with molecular dispersion had almost no inflammatory masses in the lung tissue compared to the group without molecular dispersion, and exhibited relatively uniform dispersion.
CONCLUSION
Intratracheal instillation of dispersed PAA induced neutrophil inflammation and fibrosis in the rat lung, suggesting that PAA might have pulmonary inflammogenicity and fibrogenicity. Intrapulmonary dispersion of PAA particles following intratracheal instillation studies using the molecular dispersion method was similar to that following inhalation studies.
Animals
;
Rats, Inbred F344
;
Acrylic Resins/adverse effects*
;
Rats
;
Inhalation Exposure/adverse effects*
;
Male
;
Pulmonary Fibrosis/pathology*
;
Pneumonia/pathology*
;
Lung/pathology*
;
Bronchoalveolar Lavage Fluid/cytology*
2.Effects of lunar soil simulant and Earth soil on lung injury in mice.
Xiaoxiao GONG ; Shiyue HE ; Yixiao CHEN ; Yiwei LIU ; Qiyun CHENG ; Ya CHEN ; Xinyue HU ; Zhenxing WANG ; Hui XIE
Journal of Central South University(Medical Sciences) 2025;50(8):1306-1319
OBJECTIVES:
Due to prolonged exposure to cosmic radiation and meteorite impacts, lunar surface dust forms nanoscale angular particles with strong electrostatic adsorption properties. These dust particles pose potential inhalation risks, yet their pulmonary toxicological mechanisms remain unclear. Given the need for dust exposure protection in future lunar base construction and resource development, this study established an acute exposure model using lunar soil simulant (LSS) and used Earth soil (ES; Loess from Shaanxi, China) as a comparison to investigate lung injury mechanisms.
METHODS:
C57BL/6 mice were randomly assigned to 3 groups: Phosphate buffered saline (PBS), LSS, and ES, with 5 to 7 mice per group. Mice in the LSS and ES groups received a single intratracheal instillation to induce acute inhalation exposure. Body weight was monitored for 28 days. Mice were euthanized at days 3, 7, 14, and 28 post-exposure, and peripheral blood, bronchoalveolar lavage fluid (BALF), and lung tissues were collected. Immune cell subsets in BALF were analyzed using flow cytometry. Hematoxylin-eosin (HE) staining assessed lung structure and inflammation; periodic acid-Schiff (PAS) staining evaluated airway mucus secretion; Masson staining examined collagen deposition. Real-time reverse transcription PCR (real-time RT-PCR) was used to measure the mRNA expression of inflammatory cytokines (IL-1β, IL-6, and TNF-α) and epithelial barrier genes (Occludin, Cadherin-1, and Zo-1). Lung tissues at day 7 were subjected to transcriptomic sequencing, followed by immune infiltration and pathway enrichment analyses to determine immunoregulatory mechanisms.
RESULTS:
Body weight in the ES group progressively declined after day 18 (all P<0.05), while the LSS group showed no significant changes compared with the control group. HE staining showed both LSS and ES induced inflammatory cell infiltration around airways and vasculature, which persisted for 28 days but gradually lessened over time. PAS staining revealed marked mucus hypersecretion in the LSS group at day 3, followed by gradual recovery; no significant mucus changes were observed in the ES group. Masson staining indicated no obvious pulmonary fibrosis in either group within 28 days. Real-time RT-PCR demonstrated significant upregulation of IL-1β and TNF-α in both LSS and ES groups, peaking on day 7, accompanied by downregulation of epithelial barrier genes (Occludin, Cadherin-1, and Zo-1)(all P<0.05). Transcriptomic analysis showed that both LSS and ES activated chemokine-related pathways and enriched leukocyte migration and neutrophil recruitment pathways. Further validation revealed upregulation of CXCL2 and MMP12 in the LSS group, whereas CXCL3 and MMP12 were predominantly elevated in the ES group.
CONCLUSIONS
Both LSS and ES can induce sustained lung injury and neutrophil infiltration in mice, though the underlying molecular mechanisms differ. Compared with ES, exposure to LSS additionally triggers a transient eosinophilic response, suggesting that lunar dust particles possess stronger immunostimulatory potential and higher biological toxicity.
Animals
;
Mice
;
Mice, Inbred C57BL
;
Soil
;
Lung Injury/etiology*
;
Dust
;
Bronchoalveolar Lavage Fluid
;
Moon
;
Lung/pathology*
;
Inhalation Exposure/adverse effects*
;
Male
3.Association between Organochlorine Exposures and Lung Functions Modified by Thyroid Hormones and Mediated by Inflammatory Factors among Healthy Older Adults.
Xiao Jie GUO ; Hui Min REN ; Ji Ran ZHANG ; Xiao MA ; Shi Lu TONG ; Song TANG ; Chen MAO ; Xiao Ming SHI
Biomedical and Environmental Sciences 2025;38(2):144-153
OBJECTIVE:
To examine the mechanistic of organochlorine-associated changes in lung function.
METHODS:
This study investigated 76 healthy older adults in Jinan, Shandong Province, over a five-month period. Personal exposure to organochlorines was quantified using wearable passive samplers, while inflammatory factors and thyroid hormones were analyzed from blood samples. Participants' lung function was evaluated. After stratifying participants according to their thyroid hormone levels, we analyzed the differential effects of organochlorine exposure on lung function and inflammatory factors across the low and high thyroid hormone groups. Mediation analysis was further conducted to elucidate the relationships among organochlorine exposures, inflammatory factors, and lung function.
RESULTS:
Bis (2-chloro-1-methylethyl) ether (BCIE), was negatively associated with forced vital capacity (FVC, -2.05%, 95% CI: -3.11% to -0.97%), and associated with changes in inflammatory factors such as interleukin (IL)-2, IL-7, IL-8, and IL-13 in the low thyroid hormone group. The mediation analysis indicated a mediating effect of IL-2 (15.63%, 95% CI: 0.91% to 44.64%) and IL-13 (13.94%, 95% CI: 0.52% to 41.07%) in the association between BCIE exposure and FVC.
CONCLUSION
Lung function and inflammatory factors exhibited an increased sensitivity to organochlorine exposure at lower thyroid hormone levels, with inflammatory factors potentially mediating the adverse effects of organochlorines on lung function.
Environmental Exposure
;
Hydrocarbons, Chlorinated/metabolism*
;
China
;
Ethyl Ethers/metabolism*
;
Environmental Monitoring
;
Thyroid Hormones/blood*
;
Lung/physiology*
;
Inhalation Exposure/statistics & numerical data*
;
Air Pollution/statistics & numerical data*
;
Air Pollutants/metabolism*
;
Humans
;
Male
;
Female
;
Middle Aged
;
Aged
4.Health Risks from Exposure to PM 2.5-bound Polycyclic Aromatic Hydrocarbons in Fumes Emitted from Various Cooking Styles and Their Respiratory Deposition in a City Population Stratified by Age and Sex.
Jun Feng ZHANG ; Xi CHEN ; Ke GAO ; Shui Yuan CHENG ; Wen Jiao DUAN ; Li Ying FU ; Jian Jia LI ; Shu Shu LAN ; Cui Lan FANG
Biomedical and Environmental Sciences 2025;38(10):1230-1245
OBJECTIVES:
To characterize fine particulate matter (PM 2.5)-bound polycyclic aromatic hydrocarbons (PAHs) emitted from different cooking fumes and their exposure routes and assess their health-associated impact to provide a reference for health risk prevention from PAH exposure across different age and sex groups.
METHODS:
Sixteen PM 2.5-bound PAHs emitted from 11 cooking styles were analyzed using GC-MS/MS. The health hazards of these PAHs in the Handan City population (stratified by age and sex) were predicted using the incremental lifetime cancer risk ( ILCR) model. The respiratory deposition doses ( RDDs) of the PAHs in children and adults were calculated using the PM 2.5 deposition rates in the upper airway, tracheobronchial, and alveolar regions.
RESULTS:
The total concentrations of PM 2.5-bound PAHs ranged from 61.10 to 403.80 ng/m 3. Regardless of cooking styles, the ILCR total values for adults (1.23 × 10 -6 to 3.70 × 10 -6) and older adults (1.28 × 10 -6 to 3.88 × 10 -6) exceeded the acceptable limit of 1.00 × 10 -6. With increasing age, the ILCR total value first declined and then increased, varying substantially among the population groups. Cancer risk exhibited particularly high sensitivity to short exposure to barbecue-derived PAHs under equivalent body weights. Furthermore, barbecue, Sichuan and Hunan cuisine, Chinese cuisine, and Chinese fast food were associated with higher RDDs for both adults and children.
CONCLUSION
ILCR total values exceeded the acceptable limit for both females and males of adults, with all cooking styles showing a potentially high cancer risk. Our findings serve as an important reference for refining regulatory strategies related to catering emissions and mitigating health risks associated with cooking styles.
Humans
;
Polycyclic Aromatic Hydrocarbons/analysis*
;
Cooking/methods*
;
Male
;
Female
;
Particulate Matter/analysis*
;
Adult
;
Child
;
Middle Aged
;
Air Pollutants/analysis*
;
Adolescent
;
Air Pollution, Indoor/analysis*
;
Young Adult
;
Child, Preschool
;
Aged
;
China
;
Inhalation Exposure
;
Age Factors
;
Sex Factors
;
Cities
;
Infant
5.Bronchial Response to High and Low Molecular Weight Occupational Inhalant Allergens
Lipińska-Ojrzanowska AGNIESZKA ; Nowakowska-Świrta EWA ; Wiszniewska MARTA ; Walusiak-Skorupa JOLANTA
Allergy, Asthma & Immunology Research 2020;12(1):164-170
PURPOSE: Occupational asthma may be induced by high- or low-molecular weight allergens (HMWA or LMWA, respectively). The study was conducted to compare the pattern of bronchial response in 200 HMWA-induced asthmatics (n = 130) and LMWA-induced asthmatics (n = 70). METHODS: The study participants underwent a single-blind, placebo-controlled specific inhalation challenge (SIC) with workplace allergens, accompanied by evaluation of non-specific bronchial hyperresponsiveness (NSBHR) with methacholine before and after the SIC. RESULTS: A single early bronchial response more frequently occurred in HMWA-induced asthmatics than in LMWA-induced asthmatics (86.2% vs. 20%). An isolated late bronchial response or atypical patterns were more frequently observed in LMWA-induced asthmatics than in LMWA-induced asthmatics (45.7% vs. 3.8% or 34.3% vs. 10%, respectively). Baseline NSBHR before SIC was more often detected in LMWA-induced asthmatics than in HMWA-induced asthmatics (81.4% vs. 54.6%), and the median value of the provocation concentration of methacholine was relevantly lower in these patients before and after SIC. A significant 3-fold increase in NSBHR after SIC was observed more often in LMWA-induced asthmatics than in HMWA-induced asthmatics (82.8% vs. 66.1%). In addition, compared to LMWA-induced asthmatics, HMWA-induced asthmatics were older, were more frequently active smokers, showed lower level of NSBHR, and more frequently continued their work in harmful occupational exposure. CONCLUSIONS: The results of this study suggest that HMWA-induced asthmatics may have milder clinical courses and that there is a possibility of job continuation despite asthma exacerbation requiring medical surveillance.
Allergens
;
Asthma
;
Asthma, Occupational
;
Bronchial Hyperreactivity
;
Humans
;
Immunoglobulin E
;
Inhalation
;
Methacholine Chloride
;
Molecular Weight
;
Occupational Exposure
;
Prognosis
6.Lowest observed adverse effect level of pulmonary pathological alterations due to nitrous acid exposure in guinea pigs.
Masayuki OHYAMA ; Hiroshi NISHIMURA ; Kenichi AZUMA ; Chika MINEJIMA ; Norimichi TAKENAKA ; Shuichi ADACHI
Environmental Health and Preventive Medicine 2020;25(1):56-56
BACKGROUND:
We previously demonstrated that continuous exposure to nitrous acid gas (HONO) for 4 weeks, at a concentration of 3.6 parts per million (ppm), induced pulmonary emphysema-like alterations in guinea pigs. In addition, we found that HONO affected asthma symptoms, based on the measurement of respiratory function in rats exposed to 5.8 ppm HONO. This study aimed to investigate the dose-response effects of HONO exposure on the histopathological alterations in the respiratory tract of guinea pigs to determine the lowest observed adverse effect level (LOAEL) of HONO.
METHODS:
We continuously exposed male Hartley guinea pigs (n = 5) to four different concentrations of HONO (0.0, 0.1, 0.4, and 1.7 ppm) for 4 weeks (24 h/day). We performed histopathological analysis by observing lung tissue samples. We examined samples from three guinea pigs in each group under a light microscope and measured the alveolar mean linear intercept (Lm) and the thickness of the bronchial smooth muscle layer. We further examined samples from two guinea pigs in each group under a scanning electron microscope (SEM) and a transmission electron microscope (TEM).
RESULTS:
We observed the following dose-dependent changes: pulmonary emphysema-like alterations in the centriacinar regions of alveolar ducts, significant increase in Lm in the 1.7 ppm HONO-exposure group, tendency for hyperplasia and pseudostratification of bronchial epithelial cells, and extension of the bronchial epithelial cells and smooth muscle cells in the alveolar duct regions.
CONCLUSIONS
These histopathological findings suggest that the LOAEL of HONO is < 0.1 ppm.
Alveolar Epithelial Cells
;
drug effects
;
Animals
;
Bronchi
;
drug effects
;
Dose-Response Relationship, Drug
;
Emphysema
;
chemically induced
;
Epithelial Cells
;
drug effects
;
Guinea Pigs
;
Hyperplasia
;
chemically induced
;
Inhalation Exposure
;
adverse effects
;
Lung
;
drug effects
;
pathology
;
ultrastructure
;
Male
;
Microscopy, Electron, Scanning
;
Microscopy, Electron, Transmission
;
Myocytes, Smooth Muscle
;
drug effects
;
Nitrous Acid
;
toxicity
7.Health effects and consultations about radon exposure
Songwon SEO ; Jin Kyu KANG ; Dalnim LEE ; Young Woo JIN
Journal of the Korean Medical Association 2019;62(7):376-382
Radon is a naturally occurring radioactive material classified as a carcinogen by the World Health Organization, and is known to be the factor with the second-greatest impact on lung cancer after smoking. An association between radon and lung cancer has consistently been reported in epidemiological studies on mine workers and residents of homes with indoor radon exposure. However, associations between radon and other diseases, such as leukemia and thyroid cancer, have yet to be confirmed due to a lack of consistent research findings and biological relevance. Such associations are unlikely because there is a very low likelihood that organs other than the lungs are exposed to radon upon inhalation due to the short half-life of radon and its progeny and the low permeability of alpha rays. In spring 2018, the radon bed mattress incident occurred, leading to a spike of concern and interest among the public regarding the health effects of radiation exposure. This paper presents a description of radon exposure and its health effects based on the current literature and provides practical information based on health consultations experienced following the 2018 radon mattress incident.
Alpha Particles
;
Epidemiologic Studies
;
Half-Life
;
Inhalation
;
Leukemia
;
Lung
;
Lung Neoplasms
;
Miners
;
Permeability
;
Radiation Exposure
;
Radon
;
Referral and Consultation
;
Smoke
;
Smoking
;
Thyroid Neoplasms
;
World Health Organization
8.Outbreak investigation of lead neurotoxicity in children from artificial jewelry cottage industry.
Akhil D GOEL ; Rohini V CHOWGULE
Environmental Health and Preventive Medicine 2019;24(1):30-30
BACKGROUND:
Although lead neurotoxicity is a known phenomenon, it can often be missed at a primary or secondary care level especially if detailed environmental exposure history is missed.
METHODS:
This is an outbreak investigation where we observed 15 pediatric cases with neurologic signs and symptoms clustered in a slum area known for an unorganized artificial jewelry industry. Their clinical, biochemical, and epidemiological features were compared with 14 other children from the same region reporting with non-neurological symptoms who were considered as unmatched controls.
RESULTS:
Cases with neurological manifestations had a higher in-house lead smelting activity [OR 7.2 (95% CI 1.4-38.3)] as compared to controls. Toddlers below 3 years of age were more vulnerable to the effects of lead.
CONCLUSION
This study emphasizes that many focal sources of lead poisoning still remain especially in the unorganized sector. In cases presenting with unexplained neurotoxicity, specific occupational and environmental inquiry for chemical poisoning, with special consideration for lead, should be actively pursued.
Adolescent
;
Air Pollution, Indoor
;
adverse effects
;
Case-Control Studies
;
Child
;
Child, Preschool
;
Disease Outbreaks
;
Female
;
Humans
;
India
;
epidemiology
;
Infant
;
Inhalation Exposure
;
adverse effects
;
Jewelry
;
poisoning
;
Lead
;
blood
;
standards
;
Lead Poisoning
;
epidemiology
;
pathology
;
physiopathology
;
Male
;
Metallurgy
;
Neurotoxicity Syndromes
;
epidemiology
;
pathology
;
physiopathology
;
Poverty Areas
;
Risk Factors
9.Health Effects of Radon Exposure
Jin Kyu KANG ; Songwon SEO ; Young Woo JIN
Yonsei Medical Journal 2019;60(7):597-603
Radon is a naturally occurring radioactive material that is formed as the decay product of uranium and thorium, and is estimated to contribute to approximately half of the average annual natural background radiation. When inhaled, it damages the lungs during radioactive decay and affects the human body. Through many epidemiological studies regarding occupational exposure among miners and residential exposure among the general population, radon has been scientifically proven to cause lung cancer, and radon exposure is the second most common cause of lung cancer after cigarette smoking. However, it is unclear whether radon exposure causes diseases other than lung cancer. Media reports have often dealt with radon exposure in relation to health problems, although public attention has been limited to a one-off period. However, recently in Korea, social interest and concern about radon exposure and its health effects have increased greatly due to mass media reports of high concentrations of radon being released from various close-to-life products, such as mattresses and beauty masks. Accordingly, this review article is intended to provide comprehensive scientific information regarding the health effects of radon exposure.
Background Radiation
;
Beauty
;
Beds
;
Epidemiologic Studies
;
Human Body
;
Inhalation Exposure
;
Korea
;
Lung
;
Lung Neoplasms
;
Masks
;
Mass Media
;
Miners
;
Occupational Exposure
;
Radon
;
Smoking
;
Thorium
;
Uranium
10.Inhalation risk assessment of naphthalene emitted from deodorant balls in public toilets
Yerin JUNG ; Pil Gon KIM ; Jung Hwan KWON
Environmental Health and Toxicology 2019;34(1):e2019005-
The inhalation of naphthalene used as deodorant balls in public toilets could be an important cancer risk factor. The atmospheric concentration of naphthalene in public toilets (C(in)) was estimated both by a polyurethane foam passive air sampler (PUF-PAS) deployed in nine public toilets in Seoul, Korea and by a steady-state indoor air quality model, including emission estimation using Monte-Carlo simulation. Based on the estimated C(in), cancer risk was also assessed for cleaning workers and the general population. The steady-state C(in) estimated using the estimated emission rate, which assumed that air exchange was the only process by which naphthalene was removed, was much greater than the C(in) value measured using PUF-PAS in nine public toilets, implying the importance of other removal processes, such as sorption to walls and the garments of visitors, as well as decreased emission rate owing to wetting of the naphthalene ball surface. The 95 percentile values of cancer risk for workers based on the estimation by PUF-PAS was 1.6×10⁻⁶, whereas those for the general public were lower than 1×10⁻⁶. The results suggested that naphthalene deodorant balls in public toilets may be an important cancer risk factor especially for the cleaning workers.
Air Pollution, Indoor
;
Clothing
;
Deodorants
;
Inhalation Exposure
;
Inhalation
;
Korea
;
Polyurethanes
;
Risk Assessment
;
Risk Factors
;
Seoul

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