• Toxicological Research
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• 제34권2호
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• pp.111-125
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• 2018

Solvents can be used in the manufacture of medicinal products provided their residual levels in the final product comply with the acceptable limits based on safety data. At worldwide level, these limits are set by the "Guideline Q3C (R6) on impurities: guideline for residual solvents" issued by the ICH. Diisopropyl ether (DIPE) is a widely used solvent but the possibility of using it in the pharmaceutical manufacture is uncertain because the ICH Q3C guideline includes it in the group of solvents for which "no adequate toxicological data on which to base a Permitted Daily Exposure (PDE) was found". We performed a risk assessment of DIPE based on available toxicological data, after carefully assessing their reliability using the Klimisch score approach. We found sufficiently reliable studies investigating subchronic, developmental, neurological toxicity and carcinogenicity in rats and genotoxicity in vitro. Recent studies also investigated a wide array of toxic effects of gasoline/DIPE mixtures as compared to gasoline alone, thus allowing identifying the effects of DIPE itself. These data allowed a comprehensive toxicological evaluation of DIPE. The main target organs of DIPE toxicity were liver and kidney. DIPE was not teratogen and had no genotoxic effects, either in vitro or in vivo. However, it appeared to increase the number of malignant tumors in rats. Therefore, DIPE could be considered as a non-genotoxic animal carcinogen and a PDE of 0.98 mg/day was calculated based on the lowest No Observed Effect Level (NOEL) value of $356mg/m^3$ (corresponding to 49 mg/kg/day) for maternal toxicity in developmental rat toxicity study. In a worst-case scenario, using an exceedingly high daily dose of 10 g/day, allowed DIPE concentration in pharmaceutical substances would be 98 ppm, which is in the range of concentration limits for ICH Q3C guideline class 2 solvents. This result might be considered for regulatory decisions.

• 대한예방의학회:학술대회논문집
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• 대한예방의학회 1995년도 제47차 추계 학술대회 연제집
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• pp.265-266
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• 1995

• 한국산업보건학회지
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• 제26권3호
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• pp.307-316
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• 2016

Objectives: In general, NIOSH method 5506 is most widely used for the occupational exposure measurement of PAHs, but 2-4 ring PAHs have poor desorption efficiency, especially for a filter. The purpose of this study was to determine a method to increase the desorption efficiency of 16-PAHs using an ultrasonic extraction procedure. Methods: Test samples prepared spiked XAD-2 tubes and PTFE filters in the range of $0.01-1.0{\mu}g/mL$ for desorption efficiency study. Four different extraction solvents, acetonitrile, acetone, tetrahydrofuran and dichloromethane, were tested in order to select the most suitable solvent for the extraction of the 16 PAHs. The addition of dimethyl sulfoxide and sonication time were considered in order to determine the method with the highest extraction efficiency. All samples were made in three sets and analysis was replicated seven times by HPLC. Results: Acetonitrile and acetone were the optimized as an extraction solvent and desorption efficiency of 2-ring PAHs such as naphthalene, acenaphthylene were increased 3~19% with dimethyl sulfoxide for XAD-2. Acetone was the best extraction solvent for PTFE filter and the desorption efficiency was increased 3~13% for 2- to 4-ring PAHs. The optimum sonication time was 60 minutes and desorption efficiency increased with extraction time. Conclusions: As a result, the best extraction solvent was acetone with dimethyl sulfoxide for ultrasonic extraction procedure and the desorption efficiency of this method was better than NIOSH 5506's. This study could be applied as a method for occupational exposure measurement of PAHs.

• Journal of Preventive Medicine and Public Health
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• 제27권3호
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• pp.487-504
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• 1994

A cross-sectional study was performed to evaluate the effects of chronic low-dose solvent on neurobehavioral performance of 118 male car painters. A control group of 113 workers matched for age was selected from different sections of the factory. The mean age and the mean duration of employment were 33 years and 6.7 years in both groups. Mean years of education were 11.4 years in car painters and 11.8 years in controls. Each worker completed a medical and occupational questionnaire and four tests of Swedish performance evaluation system. These included simple reaction time, symbol digit, digit span and finger tapping speed. Althougth the mean duration of employment was 6.7 years, comparison of mean performance showed a significantly poorer performance on simple reaction time (p<0.05), symbol digit(p<0.01) and digit span(p<0.05) in car painters. In univariate analysis, age and educational level contributed to poorer performance on symbol digit and digit span. Smoking appeared to slow finger tapping speed in car painters. Performance of four tests of car painters exposed to high level of solvent was poorer than that of car painters exposed to low level. In multiple regression models, controlling for age, alcohol, smoking and shift work, solvent exposure was found to be associated with performance of simple reaction time, symbol digit and digit span and exposure to high level of solvent was related to poorer performance of symbol digit and digit span.

• 한국산업보건학회지
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• 제1권2호
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• pp.192-199
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• 1991

Biological exposure indices (BEI) of toluene, perchloroethylene (PCE) and methyl ethyl ketone (MEK) for Korean workers were studied respectively. Environmental exposures in workplace to organic solvent were measured by personal sampling. Blood toluene, blood perchloroethylene, urinary trichloroacetic acid and urinary MEK were determined by headspace gas chromatography. Urinary hippuric acid were determined by HPLC and corrected by creatinine. BEIs for Korean workers were calculated as the levels of determinants which are correspond to permissible exposure limits in Korea. Blood toluene level of 2.2mg/l and urinary hippuric acid level of 1.7g/g creatinine are correspond to an exposure of 100 ppm toluene. Blood PCE concentration of 1.6mg/l and urinary trichloroacetic acid concentration of 2.9mg/l are correspond to an exposure of 50ppm PCE. Urinary MEK concentration of 1.0mg/l is correspond to an exposure of 200ppm of MEK. BEIs for Korean workers determined in this study are very different to ACGIH's BEI as urinary determinants are much lower and blood determinants are much higher than ACGIH's BEI.

• Journal of Preventive Medicine and Public Health
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• 제31권4호
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• pp.628-643
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• 1998

To investigate the exposure levels of organic solvents and subjective symptoms of dry-cleaning workers, 77 male and 52 female dry-cleaning workers who had been worked in a small city of Chungnam province, and a large city, Taejon were selected for the study group. Air concentrations of organic solvents in the working environment were analyzed, and subjective symptoms of dry-cleaning workers were surveyed, from July to August 1996. The results obtained were as follows : 1. The concentrations of organic solvents in the working environment were within permissible TLV-TWA limits. 2. For the 13 symptom clusters, the most frequently complained symptom clusters were fatigue as 71.3%, and followed by depression and urinary disturbances as 53.5% and 51.9%. Other symptom clusters complained were below 50%. 3. Positive response rates of subjective symptoms were significantly higher in worker groups such as lived in a large city, female, higher education level, more frequently alcohol drinking, higher concentration of organic solvent in working environment, work in alone. 4. Workers who had used solvent B showed 2.3 point higher scores of subjective symptoms than those of solvent A. Of the subjective symptoms scores, amnesia and nervousness were higher in solvent B user group than solvent B user group. 5. As a result of factor analysis, 3 factors such as depression, urinary disturbance and neurologic disturbance were selected. 6. As a result of the logistic regression analysis, sex, the number of fellow workers, working time, region, job tenure, smoking, alcohol drinking, ventilating system, concentration of organic solvent in working environment and place of residence were selected for the related variables. For the conclusion, even though the concentrations of organic solvents in the working environments of dry-cleaning workers were within permissible limit of TLV-TWA, many dry-cleaning workers complained symptoms, such as fatigue, depression, urinary disturbances and so on. And the factors affecting to the symptoms of dry-cleaning workers were the number of fellow workers, work hours, region, job tenure, smoking and alcohol drinking.

• 한국표면공학회:학술대회논문집
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• 한국표면공학회 2011년도 춘계학술대회 및 Fine pattern PCB 표면 처리 기술 워크샵
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• pp.42-43
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• 2011

Improvement of the photovoltaic efficiency via exposure of organic solar cells to solvent-vapor at room temperature is reported. Carbon disulfide ($CS_2$) vapor treatment can induce Poly(3-hexylthiophene) (P3HT) self-organization into ordered structure leading to enhanced hole transport and light absorption. The power conversion efficiency (PCE) of the organic solar cells can be increased from 0.89 to 1.67% by solvent-vapor treatment.

• 한국환경과학회지
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• 제18권3호
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• pp.345-353
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• 2009

The purpose of this study is to examine the health of beauty salon workers through the utilization of questionnaires concerning the extent of exposure to organic solvents found in the air of some beauty salons and any resultant symptoms in employees. The subjects were 36 employees from 10 beauty salons who agreed to participate in this study. The degree of exposure to organic solvents in the air of beauty salons was measured from September 1, 2008 to September 30, 2008. A survey of symptoms that occurred due to exposure to these solvents was also performed. The results were as follows: questionnaires were collected and analyzed from a total of 36 subjects. Of these, 28(77.8%) were female and 8(22.2%) were male. The mean age was 29.08. The mean working period was 7.13 years. Sixteen subjects attended programs at universities while 11 went to beauty schools for vocational education. When testing the concentration of organic solvents in the air of beauty salons, the highest value found was Isopropyl alcohol 511.85 ppb followed by butyl acetate, toluene, acetone, xylene, ethyl benzene, styrene, and chlorobenzene. A logistic regression analysis was performed as follows: the point of each factor was the dependent variable while sex, age, drinking, smoking, educational level, work experience, hairdresser's license, and organic solvents were the independent variables. Statistically significant difference (p<0.05) was shown in the hairdresser's license among Factor 1 and in Xylene among Factor 2; however, difference was not shown in the other variables.

• 한국산업보건학회지
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• 제3권2호
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• pp.166-176
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• 1993

In order to investingate the renal dysfunction in workers exposed to aromatic organic solvents, 105 male exposed workers and 109 controls were participated in this study. This study was conducted to examine the correlation among the concentration of aromatic organic solvents in air, worker's urinary NAG activity and urinary hippuric acid. The results were as follows : 1. The exposure level of aromatic organic solvent mixture caculated by the equation proposed by ACGIH was ranged from 0.27 to 0.54 and toluene concentration was ranged from 18.3ppm to 48.3ppm. 2. NAG activity in the urine of control and exposed group were $36.1{\pm}14.2nmolMU/mg$ creatinine and $52.4{\pm}26.1nmolMU/mg$ creatinine, respectively. Hippuric acid concentration in the urine of control and exposed group were $191.1{\pm}194.2mg/g$ creatinine and $789.3{\pm}784.1mg/g$ creatinine, respectively. 3. Correlation coefficent between the exposure level of aromatic organic solvent mixture was significantly related to urinary NAG activity(r=0.542) and urinary hippuric acid(r=0.752). 4. Correlation coefficient between NAG activity and hippuric acid concentration was 0.357. This study suggested that urinary NAG activity was a good renal function index for aromatic organic solvents exposure and urinary hippuric acid was an index for the biological monitoring of toluene exposure.

• 한국산업보건학회지
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• 제9권1호
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• pp.87-98
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• 1999

The objectives of this study were to evaluate exposures to airborne methylene chloride and postshift carboxyhemoglobin (COHb) in blood of workers engaged in processes using blowing or cleaning agents, and to investigate correlation between methylene chloride concentrations and the blood COHb levels of workers. The geometric mean (GM) of workers' exposures (8 hour-time weighted averages, TWA) to airborne methylene chloride during cleaning molds using rags wetted with the solvent in the manufacture of flexible polyurethane foam (GM = 61.4 ppm), during operating the dip tank for cleaning molds in the manufacture of lens (GM = 61.0 ppm), and during cleaning the blowing nozzles by spraying the solvent in the manufacture of shoes (GM = 117.2 ppm) were exceeded the American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value ($TLV^{(R)}$)-Time Weighted Average (TWA) (50 ppm). The COHb levels were significantly different among groups (p<0.05). The average COHh levels in blood of non-smoking workers were 2.0% in. low-level (<50 ppm) exposure group, and 3.9 % in high-level (>50ppm) exposure group. The average COHb levels in smoking workers were 3.1% in low-level exposure group, and 4.8% in high-level exposure group. The blood COHb levels of no-exposed workers to methylene chloride were 1.8% in non-smoking group, and 2.8% in smoking group. It was found that the COHb level dependeds on the methylene chloride concentration and smoking habit, and was highly correlated with methylene chloride concentration in air. The correlation coefficient was 0.81 among non-smoking workers. The estimated COHb level (3.6%) and 95% upper confidence limit (4.0%) corresponding to TLV-TWA of methylene chloride exceeded the current ACGIH Biological Exposure Index (COHb 3.5%) for carbon monoxide. The estimated COHb level (5.4%) at 100 ppm exceeded the standard (5%) recommended by National Institute for Occupational Safety and Health (NIOSH) for preventing adverse cardiovascular effect. The estimated COHb value and 95% upper confidence limit at 25 ppm of the Occupational Safety and Health. Adminstration (OSHA) Permissible Exposure Limit-TWA (PEL-TWA) were 2.6% and 3.0%, respectively. It is suggested that COHb in blood be kept below 3.0% to comply with OSHA PEL-TWA.