Environmental Health and Toxicology最新文献

A number of absurdities surrounding the humidifier disinfectant (HD) incident may have occurred because 1) a judicial system operates on the underlying false assumption that the involved parties are equals in knowledge, information and resource mobilization capabilities, regardless of respective real status as company or individual; 2) there is a lack of a system that mandates a company to prevent and actively manage possible catastrophes; 3) the regulatory scheme makes companies believe that as long as they are complying with the existing regulations, they have satisfied all of their responsibilities. I believe that this issue is an opportunity to bring about changes in the judicial redress system, the system of internal management of manufacturers, and the regulatory system of the government. The following regulation amendments are needed to move towards the changes stated above. First, legislation relating to victim relief that is applicable to the HD incident must be established. Second, a risk management system must be formed within the manufacturing company and to this end an institutional environment for the system must be established within regulatory framework. Furthermore, legislation must be passed that could punish companies themselves that have caused severe damage to individuals because they had failed to take necessary actions to avoid foreseeable harm. Finally, the framework of regulation must be changed so that the company, who has the necessary information regarding the product and the component chemicals used in the product, must self-directed experiment and assessment of the safety of their own products.

An analysis of patients and fatalities due to exposure to polyhexamethylene guanidine (PHMG) shows that PHMG causes mainly lung diseases such as pulmonary fibrosis. However, no research on the other organs has been conducted on this matter yet. So, an in-depth discussion on toxicological techniques is needed to determine whether or not PHMG is toxic to organs other than just the lungs. For the test of target organ toxicity by PHMG exposure, a toxicokinetic study must first be conducted. However, measurement method for PHMG injected into the body has not yet been established because it is not easy to analyze polymer PHMG, so related base studies on analytical technique for PHMG including radio-labeling chemistry must come first. Moreover, research on exposure-biomarker and effect-biomarker must also be conducted, primarily related to clinical application. Several limitations seem to be expected to apply the biomarker study to the patient because much time has passed after exposure to the humidifier disinfectant. It is why a more comprehensive toxicological researches must be introduced to the causality for the victims.

Objectives: A hazard assessment of di(2-ethylhexyl) phthalate (DEHP), a commonly used workplace chemical, was conducted in order to protect the occupational health of workers. A literature review, consisting of both domestic and international references, examined the chemical management system, working environment, level of exposure, and possible associated risks. This information may be utilized in the future to determine appropriate exposure levels in working environments.

Methods: Hazard assessment was performed using chemical hazard information obtained from international agencies, such as Organization for Economic Cooperation and Development-generated Screening Information Data Set and International Program on Chemical Safety. Information was obtained from surveys conducted by the Minister of Employment and Labor ("Survey on the work environment") and by the Ministry of Environment ("Survey on the circulation amount of chemicals"). Risk was determined according to exposure in workplaces and chemical hazard.

Results: In 229 workplaces over the country, 831 tons of DEHP have been used as plasticizers, insecticides, and ink solvent. Calculated 50% lethal dose values ranged from 14.2 to 50 g/kg, as determined via acute toxicity testing in rodents. Chronic carcinogenicity tests revealed cases of lung and liver degeneration, shrinkage of the testes, and liver cancer. The no-observed-adverse-effect level and the lowest-observed-adverse-effect level were determined to be 28.9 g/kg and 146.6 g/kg, respectively. The working environment assessment revealed the maximum exposure level to be 0.990 mg/m(3), as compared to the threshold exposure level of 5 mg/m(3). The relative risk of chronic toxicity and reproductive toxicity were 0.264 and 0.330, respectively, while the risk of carcinogenicity was 1.3, which is higher than the accepted safety value of one.

Conclusions: DEHP was identified as a carcinogen, and may be dangerous even at concentrations lower than the occupational exposure limit. Therefore, we suggest management of working environments, with exposure levels below 5 mg/m(3) and all workers utilizing local exhaust ventilation and respiratory protection when handling DEHP.

Objectives: Aromatase inhibitors that block estrogen synthesis are a proven first-line hormonal therapy for postmenopausal breast cancer. Although it is known that standardized extract of Ginkgo biloba (EGb761) induces anti-carcinogenic effects like the aromatase inhibitors, the effects of EGb761 on steroidogenesis have not been studied yet. Therefore, the effects of EGb761 on steroidogenesis and aromatase activity was studied using a H295R cell model, which was a good in vitro model to predict effects on human adrenal steroidogenesis.

Methods: Cortisol, aldosterone, testosterone, and 17β-estradiol were evaluated in the H295R cells by competitive enzyme-linked immunospecific assay after exposure to EGb761. Real-time polymerase chain reaction were performed to evaluate effects on critical genes in steroid hormone production, specifically cytochrome P450 (CYP11/ 17/19/21) and the hydroxysteroid dehydrogenases (3β-HSD2 and 17β-HSD1/4). Finally, aromatase activities were measured with a tritiated water-release assay and by western blotting analysis.

Results: H295R cells exposed to EGb761 (10 and 100 μg/mL) showed a significant decrease in 17β-estradiol and testosterone, but no change in aldosterone or cortisol. Genes (CYP19 and 17β-HSD1) related to the estrogen steroidogenesis were significantly decreased by EGb761. EGb761 treatment of H295R cells resulted in a significant decrease of aromatase activity as measured by the direct and indirect assays. The coding sequence/ Exon PII of CYP19 gene transcript and protein level of CYP19 were significantly decreased by EGb761.

Conclusions: These results suggest that EGb761 could regulate steroidogenesis-related genes such as CYP19 and 17β-HSD1, and lead to a decrease in 17β-estradiol and testosterone. The present study provides good information on potential therapeutic effects of EGb761 on estrogen dependent breast cancer.

Objectives: There have been developed to use targeting ability for antimicrobial, anticancerous, gene therapy and cosmetics through analysis of various membrane proteins isolated from cell organelles.

Methods: It was examined about the lysosomal membrane protein extracted from lysosome isolated from HeLa cell treated by 100 ppm melanin for 24 hours in order to find associated with targeting ability to melanin using by 2-dimensional electrophoresis.

Results: The result showed 14 up-regulated (1.5-fold) and 13 down-regulated (2.0-fold) spots in relation to melanin exposure.

Conclusions: It has been found that lysosomal membrane proteins are associated with melanin to decolorize and quantity through cellular activation of lysosome.

A simple linear model to test the hypothesis based on one-on-one relationship has been used to find the causative factors of diseases. However, we now know that not just one, but many factors from different systems such as chemical exposure, genes, epigenetic changes, and proteins are involved in the pathogenesis of chronic diseases such as diabetes mellitus. So, with availability of modern technologies to understand the intricate nature of relations among complex systems, we need to move forward to the future by taking complex systems model.