Studies on the mechanisms of chemical toxicity carried out using knockout mice lacking genes of enzymes for drug metabolism or nuclear receptor proteins were reviewed, and the studies were compared with the respective conventional mechanistic studies. While the toxicity of many hazardous chemicals was observed only in wild-type or knockout mice, which clearly showed that their toxicity was involved in the enzyme or receptor, some chemicals exhibited the same degree of toxicity in two genotypes, i.e., in both the wild strain and knockout mice, demonstrating that the enzymes or receptors are not involved in their toxicity. The use of genetically-modified animals presents not only the advantage of simultaneous evaluation of toxicity endpoints and mechanisms, but also suggests significant benefits over conventional methods using several chemicals to elucidate toxicity mechanisms. Elucidation of the mechanism of toxicity will provide useful information for risk assessment, and the use of genetically-modified animals for this purpose will lead to the advancement of this assessment.

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To investigate the impact of overtime work, sleep duration, and perceived job characteristics on physical and mental status, a cross-sectional study was conducted on 377 workers (average age; 28 years old) in an information-technology (IT) company, engaged in consultation, system integration solution, and data management relevant to IT system. The psychophysical outcomes of overtime work were assessed using the Hamilton Depression Scale (HDS), Profile of Mood Status (POMS), major physical symptoms, and overtime work data for the preceding three-months. Sleep duration was directly asked by a physician. A job strain index was defined as the ratio of job-demands to job-control scores evaluated using the Job Content Questionnaire (JCQ). In a univariate analysis, overtime work was significantly related with HDS scores, POMS anger-hostility scores, and the total physical symptom count in both sexes (all p<0.05), but not in multiple regression models, after controlling for sleep duration and the job strain index. Sleep duration was negatively related to the symptom count in men and to POMS tension-anxiety scores in women (both p<0.05); the job strain index was positively related to POMS anger-hostility scores in both sexes and to HDS scores and POMS tension-anxiety scores in men (all p<0.05). Although overtime work was associated with physical and mental complaints, sleep duration and the job strain index seemed to be better indicators for physical and mental distress in overloaded workers.

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Objectives: In order to clarify the involvement in the nervous system by cervico-brachial disorders (CBD), we performed neurophysiological tests on the peripheral nervous system (PNS) and the central nervous system (CNS) in patients with CBD, subclinicals and healthy controls. Subjects and Methods: We employed antidromic sensory nerve conduction velocities (SCV) in the hands and fingers for PNS function and event-related potentials (P300) for CNS higher function. Subjects for SCV were 27 patients, 14 workers with sign and symptoms of CBD (subclinicals) and 22 controls. Subjects for P300 were 23 patients, 12 subclinicals and 10 healthy controls. Conclusions: In the PNS, since significant reduction SCV in the index finger among patients was observed, we could not find clear evidence of decrease of conduction function. In the CNS, since the latencies and amplitudes of auditory P300 among patients were significantly delayed and decreased, respectively, and the latencies significantly correlated with symptom score, it was suggested that the dysfunction of the cognition and memory function. However, further investigation is necessary to clarify the mechanism.

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Objective: Identify risk factors for musculoskeletal symptoms among call center operators of a bank in São Paulo, Brazil. Methods: Ergonomic work analysis was carried out, involving work observation and interviews. Self-answered questionnaires performed by 108 call center operators. Results: Women represented 88% of the call center operators, 70% of them were in the age bracket of 18 to 23 yr. Daily working time was 6-h with one 30 min break. Workers remained seated 95% of the time, typing and answering telephone calls. Men's work consisted of more active telemarketing and women's of customer services. Among female operators the prevalence of neck/shoulder symptoms was 43% (95% CI, 33-53) and of wrist/hand was 39% (95% CI, 29-49). Risk factors associated with wrist/hand symptoms were: inadequate height of table (Odds ratio (OR) 3.67, 95% CI, 1.12-11.96) and to answer above 140 calls/d (OR 3.36, 95% CI, 1.16-9.71). Risk factors associated with neck/shoulder symptoms were making fewer rest breaks (OR 3.17, 95% CI, 1.11-8.97) and inadequate thermal comfort (OR 3.06, 95% CI, 1.09-8.62). Conclusions: Prevention of musculoskeletal disorders among call center operators requires an integrated approach including improved workstation design, thermal comfort environment, well-scheduled work-rest regime and realistic production goals.

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The incidence of work-related musculoskeletal disorder including low back pain sharply increased since 2000 in Korea. The objectives of the present study are to compare disability duration of lumbar intervertebral disc displacement among types of insurances, and to obtain its appropriate duration. The medical records of all patients whose final diagnosis in discharge summary of chart was lumber specified intervertebral disc displacement (LIVD) in 6 large general hospitals in Korea were reviewed to compare the length of admission and disability among different types of insurances. The information on age, gender, the length of admission, the length of follow-up for LIVD, occupation, operation, combined musculoskeletal diseases, and type of insurance was investigated. 552 cases were selected and analyzed to calculate arithmetic mean, median, mode, and geometric mean of disability duration. There was a significant difference in the length of admission and disability among types of insurance after controlling covariates such as age and combined diseases by the analysis of covariance. The length of admission in cases of IACI and AI was much longer than that of HI, and the length of disability in cases of IACI was much longer than that of HI. Prolonged duration of admission and disability was not assumed due to combined diseases, complication or other unexplainable personal factors in cases of those with industrial accidents compensation insurance and automobile insurance. This means that proper management of evidence-based disability duration guidelines is urgently needed in Korea.

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The ambient air quality monitoring was carried during the May 2003 to April 2004 along the (NH-6) passing through Jalgaon city. The average concentration of SOx 64 μg/m³, NOx 58 μg/m³, particulates (>10 μ) 515 μg/m³ and respirable dust particulates 224 μg/m³ was reported at Prabhat during the study period (May 2003-April 2004). This location represents the major highway crossings (four) in the study area. The present investigations are on the survey of health status and lung function of traffic policemen exposed to the inferior air quality as observed on the highway crossings. The spirometric analysis of traffic policemen shows significant variation in Peak Expiratory Flow Rate (PEFR), Forced Expiratory Volume in one second (FEV₁) and Forced Vital Capacity (FVC). The parameters were significantly affected in the traffic policemen as against the control group of population. It reveals significant respiratory impairment in the traffic policemen due to exposure to vehicular pollution. The study suggest the compulsory use of personal protective equipment (nose mask) by the traffic policemen during duty hours will help for the protection from vehicular pollution. The regular periodic health checkup is required to understand the impact of vehicular pollution on the health of traffic policemen.

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Manganese-induced early biochemical changes and effects of supplementation of magnesium nitrate (Mg(NO₃)₂) and antioxidant vitamins (A, C, D and E) were studied in rats intoxicated with manganese. Significant elevation in the level of chlorides in plasma, erythrocytes, liver and cerebellum, and a decrease in plasma inorganic phosphate (pi) with an increase in liver pi were observed in animals exposed to manganese as compared to controls. The level of erythrocyteacid labile phosphate (ALP), nicotinamide adeninedinucleotide (NAD⁺) and plasma sialic acid (N-acetylneuraminic acid, NANA) also increased significantly. Elevated levels of chlorides in plasma, erythrocytes and cerebellum reversed to normal control values whereas liver chlorides restored partially by the supplementation of Mg(NO₃)₂. Vitamins supplementation was effective to reverse chlorides level in erythrocytes, liver and cerebellum. Decreased level of pi in plasma and the highly elevated level of erythrocyte ALP were also recovered in animals received Mg(NO₃)₂ in addition to MnSO₄. However, such effect of Mg(NO₃)₂ was not seen in lowering the elevated level of NANA that restored by the administration of vitamins. Thus, the early alterations in plasma levels of chlorides, pi, and NANA and erythrocyte-ALP seem to be an indicative of early manganese toxicity while Mg(NO₃)₂ and vitamins supplementation appear to provide, at least in part, protection against manganese toxicity.

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In Thailand, agriculture is one of the major occupations; however, there is no comprehensive agricultural occupational health promotion and disease prevention model available. Objectives of this study were to empower farmers to study occupational health and safety situation in rice farming and to develop model to promote their health and prevent occupational health hazards among them. This participatory action research was performed in Tambol Klong 7, Klongluang district, Pathumthani, Thailand. The 24 rice farmers from 9 villages were voluntarily recruited as members of research team called farmer-leader research group. This group had a monthly meeting to discuss issues of agricultural occupational health and safety during 3 yr study period. At first stage, farmer-leader research group analyzed occupational health and safety during rice farming process. After we had results from situation analysis, farmer-leader research group decided which problems would be solved first. We developed model to solve those problems during the second stage. Finally, model was implemented to farmers in the study area. During first stage, results of questionnaires showed that there were 3 major occupational health and safety problems among these farmers; symptoms from pesticide exposure (65% of respondents), musculoskeletal problems during various process (16.6%-75.9%), and injuries during various process (1.1%-83.2%). From these results, farmer-leader research group decided to deal with pesticide problem. There was an experiment comparing using biofertilizers and bio pest-control with using chemical fertilizers and pesticides in the rice paddy. Results showed that the biological field produced the same amount of rice as the chemical field but cost less money than the chemical one. Benefits from using biofertilizers and bio pest-control were having higher profit, less exposure to chemicals, and good mental health from higher profit. After this experiment, biofertilizers and bio pest-control were disseminated to rice-farmers and students and teachers in local schools. At the end of study, we found that there were networks of farmers and networks of students-teachers using biological methods. This study showed that participation with farmers could create a real sustainable model to promote farmers' health and prevent them from occupational health hazards.

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Processes and conditions of production may produce unhealthy effects. Both must therefore be included in the education of health care personnel. Vocational training in occupational health at Kocaeli University Medical School, Turkey aims to demonstrate students that occupational health is a specific and important area of work within the context of primary health care. This research is a cross-sectional study. It was planned as a three stage study: 1- reviewing literature and grouping of countries according to their occupational health curricula; 2- reviewing the occupational health programs of medical schools in Turkey, and 3- recommendations for an occupational health curriculum to include an occupational health vocational training period of one week in the two month public health education program for medical interns. During this experience, senior students would be assigned to workplace health units. Of 283 medical schools found on the web, with occupational health teaching, only 20 have a curriculum that includes training in workplace health care units. In Turkey, there is no structured practical education on occupational health. In the third part of this study, we initiated at Kocaeli University School of Medicine's curriculum, a new occupational health education model applied in the workplace health units of factories. Practical experience of occupational health in the workplace is useful in introducing the community-based approach to occupational health in undergraduate medical education and understanding the determinants of health in industry.

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Bisphenol A (BPA), a xenoestrogen, has been reported to mimic the actions of estrogen or to affect the endocrine glands in vivo and in vitro. In this study, we examined whether in utero and lactational exposure to BPA alters thyroid status in rat F₁ offspring. Dams were orally administered various doses of BPA (0, 4 or 40 mg/kg body weight per day) from gestation day (GD) 6 through postnatal day (PND) 20. The BPA and control groups did not differ significantly with respect to plasma thyroxine (T₄) concentration. The thyroid glands from the BPA groups had normal T₄ responses to exogenous thyroid-stimulating hormone in vivo. These results suggest that in utero and lactational exposure (indirect exposure) to BPA (4-40 mg/kg/day, GD 6-PND 20) does not affect thyroid functions in the F₁ generation of male and female rats.

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Both traditional colorimetry and recently developed HPLC-fluorometry have been in use for determination of δ-aminolevulinic acid in urine (ALA-U), an effect marker of occupational exposure to lead (Pb). The present study was initiated to compare the values by the two methods on an epidemiology basis among workers occupationally exposed to lead (Pb), to estimate quantitatively the colorimetry-associated increment over the values by the HPLC method, to evaluate ALA-U determination in occupational health service for Pb-exposed workers, and to identify a critical Pb-B to induce an elevation in ALA-U. For this purpose, blood and urine samples were collected from three groups of Pb-exposed workers (both men and women in combination, including smokers) and analyzed for Pb in blood (Pb-B; measured in all subjects) and ALA-U (by colorimetry or HPLC), i.e., Group 1 (164 subjects with urinalysis by the two methods), Group 2 (2,923 subjects by colorimetry), and Group 3 (2,540 subjects by HPLC). ALA-U when measured by colorimetry was higher than the values by HPLC, and that the mean difference on a group basis was 1.4 mg/l (in a range of 1.1 to 1.8 mg/l), irrespective of Pb-B levels. It was also found that the increase in ALA-U was small when Pb-B was relatively low (e.g., ≤40 μg/100 ml), and that the increase on a group basis in response to an increase in Pb-B from 5 to 40 μg/100 ml was as small as ≤0.6 mg/l. Thus, ALA-U appeared to be not a sensitive marker of Pb effects at low Pb-B levels. ALA-U however increased substantially with a point of inflection at the Pb-B level of about 17-34 μg/100 ml. Thus it was concluded that ALA-U as measured by colorimetry is greater than ALA-U by HPLC by 1.4 mg/l on average irrespective of intensity of Pb-exposure, which may induce bias in evaluation of health effect, and that ALA-U levels will increase when Pb-B is in excess of 17-34 μg/100 ml.

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To identify mutagens formed in a model reaction of lipid peroxidation, linolenic acid methyl ester and hemin were reacted with dG. As a result, a 4-oxo-2-hexenal-dG adduct (dG^*) was identified in the model reaction mixture. The 4-oxo-2-hexenal (4-OHE) showed mutagenic activity in the Salmonella typhimurium strains TA100 and TA104. After 4-OHE was orally administered to mice, dG^*, 4-OHE-dC- and 4-OHE-5-methyl-dC adducts were detected in esophageal, stomach and intestinal DNA. In the vapor phase released from the methyl linolenate-hemin model system, and in the smoke released during the broiling of fish, 4-OHE was detected by GCMS. The 4-OHE seems to be produced by the auto-oxidation of ω-3 polyunsaturated fatty acids. These results provide a warning to workers dealing with ω-3 fats, who may be exposed to this volatile mutagen.

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This research was conducted to determine formaldehyde exposure of staffs in pathology laboratories, surgery rooms and endoscopy wards in eight large hospitals of Tehran University of Medical Sciences located at Tehran, Iran. Air sampling have been made by both long and shortterm methods. Total numbers of samples were 160 for both methods. Nineteen samples of 160 samples were collected as blank in other non-exposed environments such as administrative sections. The mean (SD) levels of formaldehyde in long-term methods were 0.96 (0.74), 0.25 (0.21) and 0.13 (0.18) ppm, at pathology laboratories, surgery rooms and endoscopy wards, respectively. The results of measurements showed that mean (SD) concentration of formaldehyde in one hour sampling at short intervals were 0.83 (0.29), 0.23 (0.16) and 0.75 (0.25) ppm at pathology labs, surgery rooms and endoscopy wards, respectively. There were significant differences in the mean levels of formaldehyde (long-term) at surgery rooms (p<0.02) and endoscopy wards (p<0.005) in eight hospitals of this study. It is concluded that the concentration levels of formaldehyde at pathology laboratories exceeded recommended limit which established by the American Conference of Governmental and Industrial Hygienists ACGIH (TLV-C=0.3 ppm). It is recommended that local exhaust ventilation should be installed to minimize the contact to formaldehyde in the staffs.

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To implement a globally harmonized system of classification and labelling of chemicals (GHS) in Korea, an interminsterial GHS committee involving 6 ministries established an expert working group composed of 7 experts from relevant organizations and one private consultant to prepare an official Korean GHS version by March, 2005. As such, the translation and review of the official Korean GHS version, including annexes, started in October, 2004 and was completed on March 15, 2005. The official Korean GHS version has now been posted on the websites of the relevant ministries and organizations to solicit public opinions. The official Korean GHS version will be finalized after a public hearing scheduled for May, 2005. Collaborative efforts as regards implementing and disseminating the GHS in Korea will be continued to avoid any confusion or duplication and for effective use of resources.

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