Effects of occupational trichloroethylene exposure on cytokine levels in workers

OBJECTIVE: We sought to investigate trichloroethylene-induced alterations of the immune system in humans. METHODS: The levels of interleukin-2, interleukin-4, and interferon-gamma in sera obtained from workers exposed to trichloroethylene were determined and compared with those of internal and external control subjects. RESULTS: In workers with a mean urinary trichloroacetic acid concentration of 13.3 +/- 5.9 mg/g creatinine, exposed to a mean environmental trichloroethylene level of 35 +/- 14 mg/m, we observed a significant increase in sera interleukin-2 and interferon-gamma levels and a reduction in interleukin-4 concentrations compared with those of workers from the internal and external control groups. CONCLUSIONS: This study provides the first report on quantitative immune changes induced by occupational exposure to low levels of trichloroethylene and strongly suggests that exposure to this substance alters immunohomeostasis in humans with possible effects on health.     

Effects of exposure to trichloroethylene and noise on hearing in rats

Four groups of rats (n=8 per group) were exposed to either 3000 ppm trichloroethylene (TCE) alone or to 95 dB SPL noise alone or to the combination of TCE and noise or to control conditions. Exposure was carried out 18 hours/day, 5 days/week for 3 weeks. Exposure to TCE alone resulted in hearing loss at 4, 8, 16 and 20 kHz, but not at 24 and 32 kHz. Hearing loss due to exposure to noise alone occurred at frequencies of 8, 16 and 20 kHz. In general, combined exposure to TCE and noise resulted in larger auditory threshold changes than that produced by either TCE alone or noise alone when measured 1 and 2 weeks after the completion of exposure. For frequencies of 8, 16 and 20 kHz, hearing loss due to combined TCE-noise exposure was not larger than the algebraic sum of hearing loss due to exposure to TCE or noise alone. However, at a frequency of 4 kHz, hearing loss due to combined exposure was significantly larger than that produced by TCE exposure alone or noise alone, which itself had no effect at this frequency. These results suggest evidence of an interaction of combined exposure to TCE and noise at the lower edge of the range of frequencies affected.     

Effects of androgen treatment in impotent men with normal and low levels of free testosterone

The relation between sexual function and serum free testosterone (fT) levels, which represent the active fraction of circulating testosterone, was evaluated. Two groups of impotent male subjects with mild hypogonadism were treated with oral testosterone undecanoate (TU); these men presented with tT/luteinizing hormone (LH) ratio and tT levels at the lower limits of normal. The first group had serum fT below 6.6 ng/ml, considered the lower normal value, according to our laboratory method, whereas the second group had normal fT limits. Administration of TU improved sexual function only in impotent men with low fT levels, but not in subjects with normal fT levels, even though the tT levels and the tT/LH ratio of the two groups were not significantly different. The results of our study suggest the presence of a minimun serum fT threshold, lying near the lower normal range, which determines the male sexual function. Moreover, serum fT levels were a more sensitive index than tT for identifying impotent men who can be successfully treated with androgens.     

Effects of luteinizing hormone-releasing hormone on sexual arousal in normal men

Six normal adult male subjects were administered either luteinizing hormone-releasing hormone (LRH, 500 µg, intramuscularly injected) or a saline placebo 10 min before a 40-min laboratory session in which they were exposed to erotic stimuli; subjects attended four such sessions, twice receiving LRH and twice the placebo in a balanced, double-blind, crossover design. Sexual arousal was inferred from degree of tumescence, with penile circumference measured by a mercury-in-rubber strain gauge. Heart rate was monitored continuously, and blood samples were taken periodically and assayed for serum luteinizing hormone (LH), follicle stimulating hormone (FSH), and testosterone (T). Rapidity of onset of erection, maximum degree of erection obtained, and overall levels of tumescence were consistently greater following LRH administration than following saline placebo; however, the differences were not statistically significant. The anticipated LH and FSH response to LRH was noted as well as a small increment in LH levels following erotic stimulation. No significant alteration in serum testosterone was observed within the time sampled. There were no significant correlations between hormonal data and any measurement of penile tumescence. In view of the results, further investigation of the behavioral effects of LRH appears justified.     

Effects of combined exposure to trichloroethylene and alcohol on mental capacity

Summary Adult male volunteers inhaled a constant concentration of 200 ppm trichloroethylene for 2 1/2 hours, ingested ethanol (0.35 gr/kg body weight) or were exposed to the combination of trichloroethylene and ethanol. After exposure Ss performed a few mental tasks. Performance as indicator of external load and the physiological parameters heart rate, sinus arrhythmia and in the final experiment also breathing rate as indicators of functional load were used as dependent variables. Exposure to a combination of trichloroethylene and alcohol leads to an increase of functional load while performing a mental task, even when exposure to only trichloroethylene or alcohol has no effect. Difficulties in experimental design and interpretation of research of combined stress are discussed.     

Dose-related subclinical neurobehavioral effects of chronic exposure to low levels of organic solvents.

One hundred eight-seven workers (mean age +/- SD; 42 +/- 8.8 years) in two paint manufacturing plants were examined to determine if sustained low-level exposure to mixed organic solvents resulted in the painters' syndrome (a psycho-organic syndrome). The test battery consisted of a medical and occupational questionnaire, the Present State Examination, the Zung Depression Scale, the Scandinavian Questionnaire 16, a neuropsychological battery, and vibration thresholds. Solvent exposure, expressed as total hydrocarbon of combined selected solvents, was quantitated using 13-15 years of personal breathing zone samplings. Linear regression analysis controlling for several confounding variables demonstrated significant correlations between increasing exposure to mixed organic solvents and neurobehavioral performance for vibration threshold and several neuropsychological tests. Dose-related effects of chronic solvent exposure on neurobehavioral outcomes (all subclinical) were shown, but "typical" symptoms characteristic of the painter's syndrome were not found.     

Effects of occupational solvent exposure on reproductive hormone concentrations and fecundability in men

BACKGROUND: Little is known about the effects of organic solvents on male reproductive health. To assess fertility and reproductive endocrine function in solvent-exposed men, we investigated time-to-pregnancy using a retrospective cohort design and cross-sectionally measured reproductive hormone concentrations in painters and millwrights compared to a reference group of carpenters. METHODS: Detailed occupational, exposure, medical, and time-to-pregnancy histories were obtained by telephone interview. Plasma luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone concentrations were determined by immunoassay. Exposure indices, which summarized working life exposure to total solvents, chlorinated solvents, aromatic solvents, and thinners, degreasers, varnishes, and adhesives as a category were calculated from exposure histories. RESULTS: FSH concentrations increased significantly with increasing exposure indices for all solvents and for chlorinated solvents. There were no significant associations of solvent exposure indices with LH or testosterone levels. LH, FSH, and testosterone concentrations also did not differ by job title. Using Cox regression, time-to-pregnancy was non-significantly longer in the painters and millwrights than the carpenters. There was no significant association between time-to-pregnancy and any of the solvent exposure indices; however, it should be noted that some of the pregnancies occurred more than 20 years previously, potentially reducing the reliability of the retrospectively collected pregnancy and exposure data. CONCLUSIONS: The significant associations between FSH levels and solvent exposure indices suggest the potential for adverse effects of solvent exposures on reproductive function in men.     

Effects of exposure to low levels of environmental cadmium on renal biomarkers

We conducted a study among residents of a small community contaminated with heavy metals from a defunct zinc smelter and residents from a comparison community to determine whether biologic measures of cadmium exposure were associated with biomarkers of early kidney damage. Creatinine-adjusted urinary cadmium levels did not differ between the smelter and comparison communities; thus we combined individuals from both communities (n = 361) for further analyses. The overall mean urinary cadmium level was low, 0.26 microg/g creatinine, similar to reference values observed in the U.S. general population. For children ages 6-17 years, urinary concentration of N-acetyl-beta-D-glucosaminidase (NAG), alanine aminopeptidase (AAP), and albumin were positively associated with urinary cadmium, but these associations did not remain statistically significant after adjusting for urinary creatinine and other potential confounders. For adults ages 18 or older, urinary concentration of NAG, AAP, and albumin were positively associated with urinary cadmium. The associations with NAG and AAP but not with albumin remained statistically significant after adjusting for creatinine and other potential confounders. We found a positive dose-effect relationship between levels of creatinine-adjusted urinary cadmium and NAG and AAP activity, and statistically significant differences in mean activity for these two enzymes between the highest (> or =1.0 microg cadmium/g creatinine) and the lowest (< or =0.25 microg cadmium/g creatinine) exposure groups. The findings of this study indicate that biologic measures of cadmium exposure at levels below 2.0 microg/g creatinine may produce measurable changes in kidney biomarkers.     

Effects of marginally negative energy balance on insulin binding to erythrocytes of normal men

Six healthy male volunteers were confined to a metabolic unit for 105 days. Energy intake (EI) and energy expenditure (EE) were varied in order to achieve either a marginally negative (-15%) or an equilibrated energy balance (EB), in different metabolic periods (MP) as follows: MP I: EE = 1, EI = 1, EB = 0; MP II: EE = 1, EI = 0.85, EB = -15%; MP III: EE = 0.85, EI = 0.85, EB = 0; MP IV: EE = 0.85, EI = 0.70, EB = -15%; MP VI: EE = 1.15, EI = 1.15, EB = 0; MP VII: EE = 1.15, EI = 1, EB = -15%. An egg protein formula diet was fed throughout the study. The amount given in MP I was sufficient to maintain body weight constant. Assigned physical activity consisted of regulated walking and cycling. During MP I, this physical activity accounted for 15% of the energy intake. Serum insulin, insulin binding to erythrocytes and body fat content were determined at the end of each MP. No significant changes were found in serum insulin level throughout the study, but specific insulin binding did change significantly. Binding increased with increased physical activity by 23% at the end of MP VI and an additional 35% at the end of MP VII. The maximum percentage of insulin binding to erythrocytes correlated inversely with the percentage of body fat in each MP. These data suggest that insulin binding to erythrocytes, in normal men, is sensitive to a small change in energy balance, and especially to physical activity.(ABSTRACT TRUNCATED AT 250 WORDS)     

邻苯二甲酸二(2-乙基)己酯青春前期暴露对雌性大鼠性激素水平及卵巢抗氧化系统的影响

目的研究邻苯二甲酸二(2-乙基)己酯(di-(2-ethylhexyl)phthalate,DEHP)青春前期暴露对雌性大鼠性激素水平及卵巢氧化应激指标的影响。方法将40只健康3周龄SPF级雌性SD大鼠按体重随机分为5组,分别为对照(玉米油)组和0.5、5、50、500 mg/kg DEHP暴露组,每组8只。采用经口灌胃方式进行染毒,染毒容量为1 ml/kg,每天1次,连续染毒4周。测定雌性大鼠血清、睾丸氧化应激[丙二醛(MDA)、超氧化物歧化酶(SOD)、酸性磷酸酶(ACP)、碱性磷酸酶(AKP)、过氧化氢酶(CAT)]指标以及血清、海马性激素[雌二醇、卵泡刺激素(FSH)、黄体生成素(LH)]水平。结果与对照组相比,500 mg/kg DEHP暴露组雌性大鼠卵巢MDA、ACP水平增加,差异均有统计学意义(P0.05);而各剂量DEHP暴露组雌性大鼠卵巢SOD、CAT和AKP的水平均未见明显变化。各剂量DEHP暴露组雌性大鼠血清MDA、SOD、CAT、ACP和AKP的水平与对照组相比,差异均无统计学意义(P0.05)。与对照组相比,仅0.5 mg/kg DEHP暴露组雌性大鼠海马雌二醇水平及5 mg/kg DEHP暴露组雌性大鼠血清雌二醇水平降低,差异均有统计学意义(P0.05)。与对照组相比,仅500 mg/kg DEHP暴露组雌性大鼠血清LH水平升高,差异有统计学意义(P0.05);而各剂量DEHP暴露组雌性大鼠血清FSH水平均未见明显变化。结论 DEHP青春前期暴露会导致雌性大鼠卵巢氧化应激损伤,并易引起青春期性激素分泌紊乱。     

Hematological changes in hospital workers due to chronic exposure to low levels of ethylene oxide

We conducted a cross-sectional study to determine whether occupational exposure to low levels of ethylene oxide can cause hematological abnormalities. Blood samples were collected from a group of 47 hospital workers who were exposed to ethylene oxide during a mean period of 6.6 years (standard error, 1.1). Ethylene oxide range levels measured were < 0.01 to 0.06 ppm. The control group, individually matched by age, sex, and smoking habits, consisted of 88 workers from the administrative sector. We found significant differences between the exposed and the control group in the frequency of workers with white blood cells lower than the normal range. Although there was no significant difference in the absolute mean number of the total white blood cells, we found an elevation in the absolute mean number of monocytes and eosinophils (P < 0.01) and a decrease (P < 0.01) in the absolute mean number of lymphocytes in the exposed group compared with the control group. We also found an elevation (P < 0.01) in the percentage of hematocrit and the mean absolute number of the red blood cells, and a decrease (P < 0.01) in the mean absolute number of platelets, in the exposed group compared with the control group. The mean absolute number of eosinophils, red blood cells, and percentage of hematocrit was significantly higher, and the mean absolute number of lymphocytes and platelets was significantly lower, in the subgroups with a higher cumulative dose of exposure. A positive dose-response was found between cumulative dose exposure and the absolute mean number of eosinophils. In view of our findings, we suggest that the use of complete blood cells with differential in routine medical surveillance and for early detection of hygiene problems should be reexamined with special attention to the eosinophils count.     

Neurotoxic effect of exposure to low doses of mercury

OBJECTIVES: To assess early effects on the Central Nervous System due to occupational exposure to low levels of inorganic mercury (Hg) in a multicenter nationwide cross-sectional study, including workers from chloro-alkali plants, chemical industry, thermometer and fluorescent lamp manufacturing. The contribution of non-occupational exposure to inorganic Hg from dental amalgams and to organic Hg from fish consumption was also considered. METHODS: Neuropsychological and neuroendocrine functions were examined in a population of 122 workers occupationally exposed to Hg, and 196 control subjects, not occupationally exposed to Hg. Neuropsychological functions were assessed with neurobehavioral testing including vigilance, motor and cognitive function, tremor measurements, and with symptoms concerning neuropsychological and mood assessment. Neuroendocrine functions were examined with the measurement of prolactin secretion. The target population was also characterized by the surface of dental amalgams and sea fish consumption. RESULTS: In the exposed workers the mean urinary Hg (HgU) was 10.4 +/- 6.9 (median 8.3, geometric mean 8.3, range 0.2-35.2) micrograms/g creatinine, whereas in the control group the mean HgU was 1.9 +/- 2.8 (median 1.2, geometric mean 1.2, range 0.1-33.2) micrograms/g creatinine. The results indicated homogeneous distribution of most neurobehavioral parameters among exposed and controls. On the contrary, finger tapping (p < 0.01) and the BAMT (Branches Alternate Movement Task) coordination test (p = 0.05) were associated with occupational exposure, indicating an impairment in the exposed subjects. Prolactin levels resulted significantly decreased among the exposed workers, and inversely related to HgU on an individual basis (p < 0.05). An inverse association was also observed between most neuropsychological symptoms and sea fish consumption, indicating a "beneficial effect" from eating sea fish. On the contrary, no effects were observed as a function of dental amalgams. CONCLUSIONS: In conclusion, this study supports the finding of early alterations of motor function and neuroendocrine secretion at very low exposure levels of inorganic Hg, below the current ACGIH BEI and below the most recent exposure levels reported in the literature.     

Effects of dietary fructose on plasma glucose and hormone responses in normal and hyperinsulinemic men

Twelve men with abnormally high insulin responses to a sucrose load and 12 normal men were fed diets containing 0, 7.5, or 15% of the calories as fructose for 5 weeks each. The diets contained approximately 43% of the calories as total carbohydrate, 42% as fat and 15% as protein. Mean insulin responses of the hyperinsulinemic men were initially 235% of control responses. Plasma glucose concentrations 1 hour after the sucrose load were significantly higher in hyperinsulinemic men than in controls. There were no initial differences between the two groups in glucagon or gastric inhibitory polypeptide (GIP) responses. Consumption of 7.5 and 15% Fructose diets increased fasting plasma glucose and GIP responses in both groups. Consumption of the 15% fructose diet resulted in significantly higher insulin and glucose responses than consumption of the other two diets. These results indicate that moderate levels of dietary fructose can produce undesirable changes in glucose metabolism of both normal and hyperinsulinemic men.     

Energy balance in rats given chronic hormone treatment. 1. Effects of long-acting insulin

1. Sprague-Dawley rats were injected for 16 d with long-acting insulin, and energy balance was calculated using the comparative carcass technique. Two experiments were carried out with females (starting weights 150 and 90 g respectively), and one with males (starting weight 150 g). In a fourth experiment, cytochrome c oxidase (EC 1.9.3.1) activity was measured as an indicator of the capacity for substrate oxidation. 2. Insulin increased weight gain by up to 57% (P less than 0.01 for all studies). Metabolizable energy intake (kJ/d) was also consistently higher in the treated groups, by up to 34% (P less than 0.01 for all studies). The excess weight gained by the insulin-treated rats was predominantly due to fat deposition. 3. Energy expenditure, calculated as the difference between metabolizable intake and carcass energy gain, was expressed on a whole-body basis, or relative to either metabolic body size (kg body-weight0.75) or fat-free mass. Insulin consistently raised energy expenditure, regardless of the method of expression, but this change reached statistical significance in only two of the nine comparisons. 4. Cytochrome c oxidase activity was not affected by insulin treatment in either interscapular brown adipose tissue or gastrocnemius muscle. In liver, total enzyme activity (U/tissue) was increased from 2928 (SE 162) in the controls to 3940 (SE 294) in the treated group (P less than 0.02), but specific activity (U/mg protein) was unchanged. 5. It is concluded that, despite causing substantial hyperphagia, insulin treatment only slightly increases energy expenditure in rats. The costs of increased tissue deposition may account for this change.