Imidacloprid Induces Lysosomal Dysfunction and Cell Death in Human Astrocytes and Fibroblasts-Environmental Implication of a Clinical Case Report.

Imidacloprid (IMI), a neonicotinoid insecticide, has potential cytotoxic and genotoxic effects on human and experimental models, respectively. While being an emerging environmental contaminant, occupational exposure and related cellular mechanisms are unknown. Herein, we were motivated by a specific patient case where occupational exposure to an IMI-containing plant protection product was associated with the diagnosis of Bell's palsy. The aim was to investigate the toxic effects and cellular mechanisms of IMI exposure on glial cells (D384 human astrocytes) and on human fibroblasts (AG01518). IMI-treated astrocytes showed a reduction in cell number and dose-dependent cytotoxicity at 24 h. Lower doses of IMI induced reactive oxygen species (ROS) and lysosomal membrane permeabilisation (LMP), causing apoptosis and autophagic dysfunction, while high doses caused significant necrotic cell death. Using normal fibroblasts, we found that IMI-induced autophagic dysfunction and lysosomal damage, activated lysophagy, and resulted in a compensatory increase in lysosomes. In conclusion, the observed IMI-induced effects on human glial cells and fibroblasts provide a possible link between IMI cytotoxicity and neurological complications observed clinically in the patient exposed to this neonicotinoid insecticide.

Adult onset asthma in non-allergic women working in dampness damaged buildings: A retrospective cohort study.

BACKGROUND: There is still no consensus about the association between working in dampness-damaged buildings and new onset of asthma among adults. The purpose of this study was to assess asthma in the staff of two psychiatric clinics where some premises were suffering from dampness. METHODS: A 20-year retrospective cohort study was performed using questionnaires. RESULTS: Incidence rate ratios (IRR) for asthma were non-significantly elevated (IRR = 2.3) among exposed individuals. The risk was greater among females (IRR = 3.5, 95% CI 1.0-16). IRR for non-atopic women was 8.8 (95% CI 1.4-196). Adjusting for smoking habits weakened the risks marginally (IRR = 7.3, 95% CI 1.1-167). The number of male participants was too low to draw conclusion regarding the risk for men. CONCLUSION: The results suggest that working in dampness-damaged buildings might be a possible health hazard. This finding is most pronounced in non-atopic females.

Airway symptoms and biological markers in nasal lavage fluid in subjects exposed to metalworking fluids.

BACKGROUNDS: Occurrence of airway irritation among industrial metal workers was investigated. The aims were to study the association between exposures from water-based metal working fluids (MWF) and the health outcome among the personnel, to assess potential effects on the proteome in nasal mucous membranes, and evaluate preventive actions. METHODS: The prevalence of airway symptoms related to work were examined among 271 metalworkers exposed to MWF and 24 metal workers not exposed to MWF at the same factory. At the same time, air levels of potentially harmful substances (oil mist, morpholine, monoethanolamine, formaldehyde) generated from MWF was measured. Nasal lavage fluid was collected from 13 workers and 15 controls and protein profiles were determined by a proteomic approach. RESULTS: Airway symptoms were reported in 39% of the workers exposed to MWF although the measured levels of MWF substances in the work place air were low. Highest prevalence was found among workers handling the MWF machines but also those working in the same hall were affected. Improvement of the ventilation to reduce MWF exposure lowered the prevalence of airway problems. Protein profiling showed significantly higher levels of S100-A9 and lower levels of SPLUNC1, cystatin SN, Ig J and ß2-microglobulin among workers with airway symptoms. CONCLUSIONS: This study confirms that upper airway symptoms among metal workers are a common problem and despite low levels of MWF-generated substances, effects on airway immune proteins are found. Further studies to clarify the role of specific MWF components in connection to airway inflammation and the identified biological markers are warranted.

Non-sensitising air pollution at workplaces and adult-onset asthma in the beginning of this millennium.

PURPOSE: This case-control study was undertaken to elucidate the controversy concerning whether low-level, long-term exposure to non-sensitising air pollution at workplaces may cause asthma. METHODS: A case-control study of 192 adult-onset asthma cases aged 20-65 years and 323 controls was conducted in the southeast of Sweden. Cases were identified from computerised registers from the region, diagnosed 2000-2004 and diagnoses were confirmed via medical files. Referents were randomised from the population register of the region. Exposure was monitored by a 16-page questionnaire. Special attention was devoted to identifying and in the final analyses excluding subjects exposed to sensitising agents. RESULTS: Three years or more of occupational exposure to air pollution from dust, smoke, fumes or vapours before the year of diagnosis by analyses adjusting for age yielded an increased risk for asthma (OR = 2.3, 95% CI 1.2-4.2) in men, while in women, no risk was seen. In a multiple logistic regression analysis in men without allergy in childhood, a significant risk was seen (OR = 2.8, 95% CI 1.07-7.4), when subjects exposed to identified allergens were excluded. In women, no excess risk was observed from occupational air pollution. CONCLUSION: The results of this study support an association between occupational exposure to low level non-sensitising air pollution and adult-onset asthma in men.

Epistaxis in a low level hydrogen fluoride exposed industrial staff.

OBJECTIVES: To assess the effect of exposure to hydrogen fluoride (HF) on the airway mucosa in an industrial setting. METHODS: A cross-sectional study encompassing 33 industrial workers in a flame soldering plant and 44 assembly workers unexposed to HF was performed by means of a questionnaire on symptoms and diagnosis regarding upper and lower airways as well as through conduct of a clinical examination of the exposed group. Air concentrations of HF that were monitored in winter amounted to 1.0 mg/m(3) and in summer time to 0.15 mg/m(3). RESULTS: A threefold risk for epistaxis (RR = 3.6, 95% confidence interval 1.1-11.0) was observed in the exposed group. Time from the start of exposure to HF until debut of a nose bleeding period varied from 1 month to 6 years. Mean induction (latency) time was 42 months. Mean duration of symptoms was 26 months, range 3-72 months, indicating that the exposure level in summer time was sufficient to maintain the propensity of almost daily nose bleeding. CONCLUSION: HF is an irritating vapor, even at relatively low air concentrations. We recommend an 8 hr TLV lower than 1.0 mg/m(3).

Occupational rhinitis caused by tolyltriazole in metalworking fluids.

OBJECTIVES: Exposure to metalworking fluids is known to cause mucous membrane inflammation of the airways. In this case report, the authors attempted to identify responsible components in the metalworking fluids for the rhinitis of an exposed patient. METHODS: The patient underwent two provocation tests. The first provocation was performed with the different metalworking fluids used in the factory, and the second was done double blind for some of the components in the metalworking fluids. The patient was asked to quantify her symptoms before, immediately after, 24 hours after, and finally 96 hours after the exposure. RESULTS: The patient reacted to tolyltriazole with rhinitis and headache. These symptoms started about 8 hours after the exposure and persisted for 24 hours. CONCLUSION: The double-blind provocation exposure to the components of the metalworking fluids showed that the patient reacted to the corrosion inhibitor tolyltriazole. To the authors' knowledge, no such reaction to tolyltriazole in the airways has previously been reported.

Prevalence of female genital mutilation among African women resident in the Swedish county of Ostergötland.

OBJECTIVES: To establish the prevalence of female genital mutilation (FGM) among African women resident in the Swedish County of Ostergötland and assess the types of FGM. MATERIAL AND METHODS: Three hundred and four African women aged > or = 18 years were domiciled in Ostergötland by the end of 1998. The women were invited by letter. A socio-cultural questionnaire designed to give an overall picture of FGM within a socio-economic context, and also to invite the women to an interview and examination, was sent to all African women in the county of Ostergötland. Women who gave their consent (n = 63) underwent a gynecologic examination. RESULTS: The response rate was 84%. According to the questionnaire, 68% of all the African women were genitally mutilated. The clinical examination revealed that 39 women (62%) were mutilated, 17 of them (44%) had undergone removal of part or all external genitalia and stitching ('infibulation'), 26% had undergone removal of the prepuce of the clitoris ('prepucectomy'), 23% had undergone various cultural practices on the external genitalia, and 7.7% excision of the clitoris with partial or total removal of labia minora ('clitoridectomy'). CONCLUSION: The influx of immigrants to Sweden and the other Scandinavian countries from cultures where FGM is practiced, requires that physicians and other health professionals familiarize themselves with the practice and the cultural beliefs underlying it. Sensitivity to the needs of these women as well as attention to the potential physical hazards posed by the practice are important factors in care.

Interaction between smoking and glutathione S-transferase polymorphisms in solvent-induced chronic toxic encephalopathy.

Exposure to organic solvents is still common in industrial and other work environments, and increases the risk of chronic toxic encephalopathy (CTE). Genetic variation in metabolic enzymes for solvents and other xenobiotics may modify the risk of developing toxic effects. Therefore, we investigated the presence of null genotypes for glutathione S-transferases M1 and T1 (GSTM1, GSTT1) and two genetic polymorphisms of microsomal epoxide hydrolase (mEPHX) in relation to the risk for chronic toxic encephalopathy (CTE) when exposed to solvents and smoking. We genotyped 115 patients who were classified into three categories: CTE (n = 56), incipient CTE (n = 27) and non-CTE (n = 32) patients. DNA was isolated from leucocytes and the GSTM1 and GSTT1 null genotypes were determined by multiplex-polymerase chain reaction. The two polymorphisms of mEPHX were analysed by PCR-RFLP (restriction fragment length polymorphism) based assays. All analyses were performed blindly with regard to both exposure and disease status. An increased binomial regression risk ratio = 2.5, 95% confidence interval (CI) 1.5-4.2, of the GSTM1 null genotype for CTE was found in smokers and for the GSTT1 null genotype (binomial regression risk ratio 1.5, 95% CI 1.0-2.0). In nonsmokers, the GSTM1 null genotype did not confer any risk for CTE. None of the studied mEPHX polymorphisms were associated with an increased risk for CTE. We suggest that the GSTM1 null genotype in smokers is a possible risk for solvent-induced CTE.