Toxicokinetics of methyl tert-butyl ether (MTBE) and tert-amyl methyl ether (TAME) in humans, and implications to their biological monitoring

Healthy male volunteers were exposed via inhalation to gasoline oxygenates methyl tert-butyl ether (MTBE) or tert-amyl methyl ether (TAME). The 4-hr exposures were carried out in a dynamic chamber at 25 and 75 ppm for MTBE and at 15 and 50 ppm for TAME. The overall mean pulmonary retention of MTBE was 43 +/- 2.6%; the corresponding mean for TAME was 51 +/- 3.9%. Approximately 52% of the absorbed dose of MTBE was exhaled within 44 hr following the exposure; for TAME, the corresponding figure was 30%. MTBE and TAME in blood and exhaled air reached their highest concentrations at the end of exposure, whereas the concentrations of the metabolites tert-butanol (TBA) and tert-amyl alcohol (TAA) concentrations were highest 0.5-1 hr after the exposure and then declined slowly. Two consecutive half-times were observed for the disappearance of MTBE and TAME from blood and exhaled air. The half-times for MTBE in blood were about 1.7 and 3.8 hr and those for TAME 1.2 and 4.9 hr. For TAA, a single half-time of about 6 hr best described the disappearance from blood and exhaled air; for TBA, the disappearance was slow and seemed to follow zero-order kinetics for 24 hr. In urine, maximal concentrations of MTBE and TAME were observed toward the end of exposure or slightly (< or = 1 hr) after the exposure and showed half-times of about 4 hr and 8 hr, respectively. Urinary concentrations of TAA followed first-order kinetics with a half-time of about 8 hr, whereas the disappearance of TBA was slower and showed zero-order kinetics at concentrations above approx. 10 micro mol/L. Approximately 0.2% of the inhaled dose of MTBE and 0.1% of the dose of TAME was excreted unchanged in urine, whereas the urinary excretion of free TBA and TAA was 1.2% and 0.3% within 48 hr. The blood/air and oil/blood partition coefficients, determined in vitro, were 20 and 14 for MTBE and 20 and 37 for TAME. By intrapolation from the two experimental exposure concentrations, biomonitoring action limits corresponding to an 8-hr time-weighted average (TWA) exposure of 50 ppm was estimated to be 20 micro mol/L for post-shift urinary MTBE, 1 mu mol/L for exhaled air MTBE in a post-shift sample, and 30 micro mol/L for urinary TBA in a next-morning specimen. For TAME and TAA, concentrations corresponding to an 8-hr TWA exposure at 20 ppm were estimated to be 6 micro mol/L (TAME in post-shift urine), 0.2 micro mol/L (TAME in post-shift exhaled air), and 3 micro mol/L (TAA in next morning urine).     

Global estimates of fatal work-related diseases

BACKGROUND: Work-related mortality is a relatively new concept which aims to widen occupational health and safety; to take into account not only recognized fatal occupational accidents and diseases but also other work-related deaths. Few countries in the world have a register for work-related diseases. METHODS: Estimates are calculated using baseline world mortality scenarios of all diseases for the year 2000 and attributable fractions made for work-related diseases in Finland, as adjusted. RESULTS: It is estimated that about 2 million work-related deaths take place annually. Men suffer two thirds of those deaths. The biggest groups of work-related diseases are cancers, circulatory diseases and communicable diseases. CONCLUSIONS: Information about work-related diseases is needed for prevention, as people in developed countries are working longer, and the age of retirement is being raised in many countries. As a result, workers are being exposed to different kinds of substances and working conditions for a longer time. In developing countries, work exposures may already start in infancy. Due to industrialization, workers in developing countries are facing new conditions with a lack of relevant knowledge and skills. With the help of information, nations can direct resources and skills for appropriate purposes such as regulatory measures on health and safety at work.     

Effect of surgeon's caseload on the quality of surgery and breast cancer recurrence

The aim of this study was to evaluate the effects of the caseloads of individual surgeons on breast cancer primary care and outcome. The extent of primary breast cancer and axillary surgery and the appearance of local recurrences were evaluated for 1377 women operated in Pirkanmaa region between 1.1.1997 and 31.12.2001 and followed- up at least until 31.12.2008 or death. Caseloads of each surgeon were divided into three categories: over 550, 100-200 and under 60. Breast conserving surgery was performed more often by surgeons with the highest (OR 1.32) and the middle (OR 1.54) caseload volumes compared to those with the lowest volumes (p = 0.018). Surgeons with the lowest caseloads also dissected fewer lymph nodes (mean 9.4 versus 11.2 in the highest and 10.9 in the middle caseload volumes; p ≤ 0.001). There were no differences in recurrences between the groups during the mean follow-up time of 8.9 years.     

Age- and Sex-related Differences in Rat Liver Microsomal Enzymes and their Inducibility by Toluene

Abstract: In the liver microsomes of toluene-treated and control Sprague-Dawley rats (n=148, males and females aged 13–93 days), the contents of cytochrome P-450 and b₅ and the activities of NADPH – cytochrome c reductase and four monooxygenases were studied. In male control rats, cytochrome contents and NADPH – cytochrome c reductase, aminopyrine N-demethylase and aniline hydroxylase activities increased to the age of one month, and after a slight decrease in cytochrome concentrations, the average adult level was reached by the age of two months. Aniline hydroxylase and 7-ethoxycoumarine O-deethylase activities decreased to about half at the same age period. In control female rats, the activities of aminopyrine N-demethylase and aniline hydroxylase decreased after the age of one month, and they remained at a considerably lower level in adult females than in males. The sex-dependence of other enzymes was negligible. Toluene induction was already well developed in the youngest age group of both sexes; in most cases the induced enzyme levels in young rats were as high or higher than in adults. In adult female rats, toluene induction of all enzymes was weaker than in males. In male rats, the toluene-induced level of aniline hydroxylase and 7-ethoxycoumarine O-deethylase showed deep minima at the age of 43–53 days, at the puberty of rats.     

A novel immunoassay for the determination of tartrate-resistant acid phosphatase 5b from rat serum.

Osteoclasts secrete tartrate-resistant acid phosphatase 5b (TRACP 5b) into the circulation. We have developed an immunoassay for the determination of rat TRACP 5b activity. Intra-assay variation of the immunoassay was 4.5%, interassay variation was 3.8%, dilution linearity was 104.6 +/- 7.6%, and recovery of recombinant rat TRACP was 99.1 +/- 5.8%. We studied serum TRACP 5b as a marker of bone resorption using orchidectomized (ORC) rats as a model for osteoporosis and age-matched sham-operated rats as controls in a 6-month study. After the operation, trabecular bone mineral density decreased significantly more in the ORC group than in the sham group, whereas cortical bone mineral density increased similarly in both groups. Serum TRACP 5b activity was significantly elevated within the first week after ORC, returned to the control level in the third week, and was not increased above the sham level at any of the later time points. At 6 months, trabecular bone volume was 80% lower in ORC rats than in controls. Osteoclast number per trabecular bone perimeter was slightly increased, but the absolute number of osteoclasts in trabecular bone was significantly decreased. These results suggest that absolute bone resorption is increased within the first week after ORC. Later, it is decreased because there is less bone to be resorbed. However, relative bone resorption (compared with the amount of remaining bone) is still increased, leading to further bone loss. We conclude that serum TRACP 5b is a useful marker for monitoring changes in the bone resorption rate in rat ORC model.     

Hypolipidemia and peroxisome proliferation induced by phenoxyacetic acid herbicides in rats

Male Wistar rats were treated daily by gavage with two phenoxy herbicides, 2,4-dichlorophenoxyacetic acid (2,4-D)(100-200 mg/kg body wt) and 4-chloro-2-methylphenoxyacetic acid (MCPA) (100-200 mg/kg body wt), and with the chemically different glyphosate N-phosphonomethyl glycine (300 mg/kg body wt) 5 days per week for 2 weeks. A hypolipidemic drug, clofibrate [ethyl-2-(4-chlorophenoxy)-2-methylpropionate], which is structurally related to phenoxy acids, was used as a positive control (200 mg/kg body wt). 2,4-D and MCPA had several effects similar to those of clofibrate: all three compounds induced proliferation of hepatic peroxisomes, decreased serum lipid levels, and increased hepatic carnitine acetyltransferase and catalase activities. 2,4-D and MCPA, but not clofibrate, decreased lipoprotein lipase activity in the adipose tissue to about a third of the control value but did not change the lipoprotein lipase activity in the heart muscle. The data suggest that these compounds cause hypolipidemia not by enhancing the storage of peripheral lipids in adipose tissue but by preferentially increasing lipid utilization in the liver. Glyphosate caused no peroxisome proliferation or hypolipidemia, suggesting that these effects are associated with the structural similarity between phenoxy acid herbicides and clofibrate.     

中老年职工工作能力与职业因素的关系研究

为探讨常见职业因素在中老年职工工作能力减退中所起的作用，以工作能力指数为工具，采用成组病例对照研究方法对１８０名工作能力减退的职工，及８５７名工作能力正常的职工，进行研究因素危险度的评价。结果显示，工作场所中的一些常见有害因素在研究的工作环境中更为普遍，经常暴露于粉尘，有害化学物质、噪声，振动，高温，潮湿等环境中的中老年职工发生工作能力减退的危险性增加；在易发生我伤事故的工作环境中工作也是一种有显