Renal effects of environmental and occupational lead exposure

Environmental and industrial lead exposures continue to pose major public health problems in children and in adults. Acute exposure to high concentrations of lead can result in proximal tubular damage with characteristic histologic features and manifested by glycosuria and aminoaciduria. Chronic occupational exposure to lead, or consumption of illicit alcohol adulterated with lead, has also been linked to a high incidence of renal dysfunction, which is characterized by glomerular and tubulointerstitial changes resulting in chronic renal failure, hypertension, hyperuricemia, and gout. A high incidence of nephropathy was reported during the early part of this century from Queensland, Australia, in persons with a history of childhood lead poisoning. No such sequela has been found in studies of three cohorts of lead-poisoned children from the United States. Studies in individuals with low-level lead exposure have shown a correlation between blood lead levels and serum creatinine or creatinine clearance. Chronic low-level exposure to lead is also associated with increased urinary excretion of low molecular weight proteins and lysosomal enzymes. The relationship between renal dysfunction detected by these sensitive tests and the future development of chronic renal disease remains uncertain. Epidemiologic studies have shown an association between blood lead levels and blood pressure, and hypertension is a cardinal feature of lead nephropathy. Evidence for increased body lead burden is a prerequisite for the diagnosis of lead nephropathy. Blood lead levels are a poor indicator of body lead burden and reflect recent exposure. The EDTA lead mobilization test has been used extensively in the past to assess body lead burden. It is now replaced by the less invasive in vivo X-ray fluorescence for determination of bone lead content.     

Determination of benzene and its metabolites: application in biological monitoring of environmental and occupational exposure to benzene

Methods for the biological monitoring of benzene and its metabolites in exhaled air, blood and urine are reviewed. Analysis of benzene in breath can be carried out by using an exhaled-air collection tube and direct analysis by GC or GC-MS; however, this technique is less reliable when compared to analysis using blood or urine. For the determination of non-metabolized benzene in blood and urine, GC head-space analysis is recommended. Phenol, the major metabolite of benzene can be monitored by either HPLC or GC methods. However, urinary phenol has proved to be a poor biomarker for low-level benzene exposure. Recent studies have shown that trans,trans-muconic acid, a minor metabolite of benzene can be determined using HPLC with UV detection. This biomarker can be used for detection of low-level benzene exposure. Urinary S-phenylmercapturic acid is another sensitive biomarker for benzene, but it can be detected only by GC-MS. Hydroquinone, catechol and 1,2,4-benzenetriol can be measured using HPLC with either ultraviolet or fluorimetric detection. Nevertheless, their use for low-level assessment requires further studies. Eventually, for the assessment of health risks caused by benzene, biological-exposure reference values need to be established before they can be widely used in a field setting.     

Prenatal exposure to environmental toxin: A test of the multiple effects model.

The multiple effects model of teratological exposure predicts that neonatal deficits associated with intrauterine exposure to small doses of a potentially teratogenic agent will vary considerably across individuals. This hypothesis was tested in a sample of 242 newborns exposed prenatally to low levels of polychlorinated biphenyls (PCBs) from maternal consumption of contaminated lake fish and 71 control infants whose mothers did not eat these fish. Behavioral outcomes were assessed using the Brazelton Neonatal Behavioral Assessment Scale (NABS). Contaminated fish consumption predicted motoric immaturity, poorer lability of states, a greater amount of startle, and more abnormally weak (hypoactive) reflexes. The most highly exposed Ss were more likely than controls to be classified as "worrisome" on 3 NBAS clusters. Results from a stepwise regression analysis are consistent with the multiple effects model, indicating that some affected Ss were born small and/or early, whereas others exhibited one or another of the behavioral deficits. The analysis indicated that 12.2% of the variance in contaminated fish consumption was associated with measurable neonatal deficits. (40 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

1,2- and 1,4-Cyclohexanediol: major urinary metabolites and biomarkers of exposure to cyclohexane, cyclohexanone, and cyclohexanol in humans

The metabolism and toxicokinetics of cyclohexane (CH) and cyclohexanol (CH-ol), important solvents and chemical intermediates, were studied in volunteers after 8-h periods of inhalation exposure at concentrations of 1010 and 236 mg m(-3), respectively (occupational exposure limits: CH, 1050 mg m(-3); CH-ol, 200 mg m(-3)). Of the dose of absorbed parent compounds, the yields of urinary CH-ol and 1,2- and 1,4-cyclohexanediol (CH-diol) were 0.5%, 23.4%, and 11.3%, respectively, after exposure to CH and 1.1%, 19.1%, and 8.4%, respectively, after exposure to CH-ol as determined by a gas chromatography method involving hydrolysis of glucuronide conjugates. The metabolic patterns of CH and CH-ol were very similar to that of cyclohexanone (CH-one) studied in the laboratory previously. For all three compounds, peak excretion of CH-ol occurred at the end of the exposure period, after which it decayed rapidly. Excretion curves of 1,2- and 1,4-CH-diol reached maximal values within 0-6 h postexposure, with subsequent elimination half-lives being 14-18 h. The rate-limiting step in the elimination of CH compounds from the organism is renal clearance of CH-diols. Determination of CH-diols in end-of-shift urine samples is recommended as a useful new method of biomonitoring of CH, CH-ol, and CH-one at the workplace. However, due to accumulation of CH-diols in the body during repeated exposure, quantitative relationships between the exposure and the level of CH-diols have to be adjusted according to the day of sampling during the working week.     

A study on the neurobehavioral effects of occupational exposure to organic solvents in Korean workers

Atomic absorption spectroscopy was used to assess uptake of Ag+1, Au+4, Cd+2, Cu+2, In+3, Ni+2, Pd+2, and Zn+2 by in vitro cultures of Balb/c 3T3 fibroblasts as a function of concentration of the cations in cell-culture medium. Reversibility of this uptake was also measured. Metal cations exhibited a 400-fold difference in their tendency to accumulate in the cells; In+3 tended to accumulate the most, whereas Pd+2 accumulated the least. Uptake of the cations in the cells increased linearly with the concentration of the cation in the medium for all cations up to their 50% toxicity concentrations. Reversal of this uptake was slower than that of the initial uptake for three cations studied in more detail (Cd+2, In+3, and Ni+2). The duration of the initial exposure affected the proportion of the metal cations that were retained by the cells 5 h after the cations were removed from the medium. The proportion of retained Cd+2 did not change when the initial exposure was increased from 2 h to 6 h, whereas the proportion of retained In+3 decreased and Ni+2 increased over the same period. The tendency of the cells to accumulate these cations correlated with their cytotoxic potency (measured previously).     

Intra- and inter-rater agreement in the assessment of occupational exposure to metals

RhoA/B/C and CDC42/Rac, which form two subgroups of the rho guanosine triphosphatase (GTPase) family, regulate various aspects of actin cytoskeleton organisation. In cytosol, guanosine diphosphate (GDP) dissociation inhibitor (GDI) interacts with and maintains rho GTPases in their inactive GDP-bound form. RhoGDI is a ubiquitously expressed GDI, whereas D4/LyGDI is hematopoietic cell-specific and 10-fold less potent than RhoGDI in binding to and regulating rho GTPases. We have combined microanalytical liquid chromatography with the use of specific antibodies in order to separate D4/LyGDI and RhoDGI-complexes from the cytosol of U937 cells and to demonstrate that the two GDIs associate with different rho protein partners. RhoGDI can form a complex with CDC42Hs, RhoA, Rac1 and Rac2, while none of these GTPases was found to interact with D4/LyGDI. In addition, we found that stimulation of U937 cells with phorbol ester leads to phosphorylation of D4/LyGDI. Our results suggest that LyGDI forms complexes with specific rho GTPases expressed in hematopoietic cells where it may regulate specific pathways.     

Mechanistic model predicts a U-shaped relation of radon exposure to lung cancer risk reflected in combined occupational and US residential data

A mechanistically based cytodynamic two-stage (CD2) cancer model was shown recently to predict both ecologic US county data and underground-miner data on lung-cancer mortality (LCM) vs radon concentration, indicating biological plausibility of the apparent negative dose-response relation exhibited by the ecologic data. To further investigate this hypothesis, the CD2 model was fitted to combine age-specific LCM data vs estimated radon-exposure in white females of age 40+ years in 2821 US counties during 1950-1954 using new estimates of county-specific mean residential radon exposure, and in five cohorts of underground nonsmoking miners. The negative association of radon levels and corresponding county-level LCM rates apparent in women dying in 1950-1954 (11% of whom never smoked) was also apparent in women of age 60+ years (5% of whom never smoked). The CD2 fit obtained to the combined residential and occupational data was found to predict the combined data using biologically plausible parameter values, and also to predict inverse dose-rate effects exhibited in nonsmoking miner data to which the CD2 model was not fit. These results are consistent with the hypothesis that residential radon exposure has a nonlinear U-shaped relation to LCM risk, and that current linear extrapolation models substantially overestimate such risk.     

Molecular biomarkers of early responses to environmental stressors: implications for risk assessment and public health

Resistance of Candida to azoles is an increasing problem. Susceptibility testing of Candida against fluconazole and ketoconazole is now feasible and desirable. Good correlation of resistance in vitro with clinical failure of fluconazole therapy has now been shown in mucosal candidiasis. The relationship, if any, between resistance and clinical failure in the context of invasive candidiasis is not clear at present and additional correlative work needs to be done. Monitoring of resistance trends in Candida is clearly important now.     

Recurrent heat exposure: effects on levels of plasma and urinary sodium and potassium in resting and exercising men

Heat acclimatization was induced in a group of healthy young men by walking on a treadmill (5.6 km/h, 49 degrees C/27 degrees C dry/wet bulb, 90 min/day, 7 d) and confirmed by observing significantly reduced final rectal temperatures and heart rates on the seventh day of exercise in the heat. A second group of men, paired for maximal oxygen consumption and body weight, remained sedentary under identical environmental conditions. While the mild exercise combined with the severe heat conditions induced significant hyperkalemia (p less than 0.02, minimal significance) on both the first and final days, there did occur an attenuated response with significantly (p less than 0.01) reduced plasma K+ after 45 min on the seventh day when compared with first day levels. No significant inter- or intragroup differences in plasma Na+ content of 24-h urine samples showed that men exercising in the heat retained an increased ability to conserve Na+, while sedentary individuals consistently displayed increased excretion of Na+. Thus, we concluded that even the mild exercise described herein effected hyperkalemia at each sampling time, but the level of hyperkalemia was attenuated after acclimatization, and while Na+ was conserved in the exercising men, no such adaptive processes occurred in sedentary individuals.     

Workshop on late effects of irradiation to the head and neck in infancy and childhood

A summary statement for the Workshop on Late Effects of Irradiation to the Head and Neck in Infancy and Childhood is presented. The Workshop, conducted by the National Cancer Institute with the cooperation of several other organizations, was convened to determine the present status of knowledge about thyroid disease related to irradiation of the head and neck and to develop guidelines with respect to detection, diagnosis, treatment, and followup. It was decided that surgical exploration should be considered for all palpable thyroid nodules, particularly those that are firm and clearly demarcated and appear as a "cold" area on the scan. Persons at risk because of prior irradiation to the head or neck should have regular reexaminations every one to two years.     

Exposure to phenol: analysis of environmental and urinary concentrations of phenol in a group of exposed subjects

The underlying metabolism and daily energy losses were studied in 22 patients with malignant tumours of the stomach and in 51 patients with pyloric stenosis and duodenal ulcer, preoperatively and over the first 9 days postoperatively. The preoperative studies revealed a rise in the underlying metabolism rate by 43.7 and 28.2%, respectively in the patients of both groups as compared to the metabolism in healthy individuals of the same sex, weight, height and age. Postoperatively, the underlying metabolism rate dropped in the oncological patients to the level seen in healthy people, whereas in duodenal ulcer patients the metabolic rates remained elevated. The patients' energy requirements are calculated respectively as 25-30 and 41-45 kcal per 1 kg body weight daily.     

Household and community determinants of exposure to involuntary smoking: a study of urinary cotinine in children and adolescents

The study examines the role of several potential predictors of urinary cotinine levels in a cross-sectional sample of 1,072 nonsmoking children and adolescents in Latium, Italy, during 1990-1991. As expected, there was a strong relation between passive exposure to smoking and the amount of maternal and paternal self-reported smoking. The urinary cotinine level increased with a decreasing level of paternal education and with an increasing index of household crowding; self-report of recent exposure to smoking outside the home was a strong predictor of the biologic marker. The analysis was then restricted to 346 subjects whose parents claimed that they were nonsmokers and that there were no smokers at home. In this group, however, 57 children reported some active smoking at home by their parents. Those with parents suspected to be "deceivers" had higher level of urinary cotinine than did those truly not exposed. In addition, urinary cotinine in this group was clearly associated with duration of exposure to smoking outside home. The study indicates that both factors related to family circumstances and exposure outside the household setting are strong determinants of urinary cotinine levels. The finding may be considered a direct confirmation that passive smoking among children should be viewed as a specific community responsibility.     

Brain stem evoked potentials and visual evoked potentials in relation to the length of occupational exposure to low levels of toluene

In 49 printing-press workers occupationally exposed to toluene for approximately 21.6 years, the values of BEAP and VEP parameters were examined in relation to the length of exposure. With the exception of P2 wave, there was a significant increase in the latencies of all the BEAP waves examined as well as in the interpeak latency (IPL) P3-P4, whereas IPL P4-P5 decreased significantly with the length of exposure. The amplitude of all the VEP examined decreased significantly with the length of exposure. Toluene exposure was evaluated by measuring the concentration of toluene in peripheral blood and of hippuric acid in urine on Wednesday morning prior to the workshift, and of hippuric acid in urine after the workshift on the same day. According to the average concentration of hippuric acid in urine after the workshift, the levels of toluene exposure were estimated to range from 40-60 ppm. Evoked potentials were determined on Mondays 10-12 hours after a nonworking weekend.     

Human exposure to mercury: a critical assessment of the evidence of adverse health effects

The ubiquitous nature of mercury in the environment, its global atmospheric cycling, and its toxicity to humans at levels that are uncomfortably close to exposures experienced by a proportion of the population are some of the current concerns associated with this pollutant. The purpose of this review is to critically evaluate the scientific quality of published reports involving human exposures to mercury and associated health outcomes as an aid in the risk evaluation of this chemical. A comprehensive review of the scientific literature involving human exposures to mercury was performed and each publication evaluated using a defined set of criteria that are considered standards in epidemiologic and toxicologic research. Severe, sometimes fatal, effects of mercury exposure at high levels were primarily reported as case studies. The disasters in Minamata, Japan, in the 1950s and in Iraq in 1971-1972 clearly demonstrated neurologic effects associated with ingestion of methylmercury both in adults and in infants exposed in utero. The effects were convincingly associated with methylmercury ingestion, despite limitations of the study design. Several well-conducted studies have investigated the effects of methylmercury at levels below those in the Iraq incident but have not provided clear evidence of an effect. The lower end of the dose-response curve constructed from the Iraq data therefore still needs to be confirmed. The studies of mercury exposure in the workplace were mainly of elemental or inorganic mercury, and effects that were observed at relatively low exposure levels were primarily neurologic and renal. Several studies have investigated effects associated with dental amalgam but have been rated as inconclusive because of methodologic deficiencies. In our overall evaluation, 29 of 110 occupational studies and 20 of 54 studies where exposure occurred in the natural environment provided at least suggestive evidence of an exposure-related effect.     

Cancer of the nasal cavity and paranasal sinuses and exposure to environmental tobacco smoke in pet dogs

PURPOSE: To evaluate dynamic MR imaging of the pituitary gland. MATERIAL AND METHODS: 19 patients with suspected mass lesions of the pituitary gland were examined at 1.5 Tesla with dynamic and standard MRI using a Turbo-FLASH sequence (1 image/s for 40 s). RESULTS: In 13/19 patients microadenomas were detected. One of the 13 microadenomas was detected using dynamic imaging and was not seen on standard MRI. The remaining 12 microadenomas were diagnosed with standard MRI. CONCLUSION: Dynamic imaging of the pituitary gland is a time-consuming and costly diagnostic technique. If laboratory results suggest the presence of a microadenoma and conventional MRI is unable to localise it, dynamic imaging should be performed.