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Environmental exposure, chlorinated drinking water, and bladder cancer.

Environmental and/or occupational factors have been proposed to play a critical role in urological malignancies and, in particular, in bladder cancer. Epidemiological studies have demonstrated with sufficient evidence that factors such as smoking and exposure to aromatic amines, paints and solvents, leather dust, inks, some metals, polycyclic aromatic hydrocarbons, combustion products, or diesel exhaust fumes are associated with the development of bladder cancer. Candidates with an uncertain potential for inducing this type of cancer include dietary factors, specifically fats and cholesterol, and the exposure to contaminants in drinking water. This chapter will describe and discuss the respective literature on environmental and occupational factors linked to carcinogenesis in bladder cancer. For several reasons, the potential effects of tea and coffee consumption will also be considered. A solid epidemiological evaluation of environmental and occupational factors linked to carcinogenesis has to meet many challenges: the number of confounding factors is often large, exposure needs to be determined retrospectively, and elevation of the attributable risk is low in most cases. In view of the long-term exposure of the vast majority of the population to, for instance, drinking- water contaminants, however, the impact of even small elevations of risk warrants evaluation. This complex task needs comprehensive approaches on a large scale including modern analytical, molecular biological and epidemiological methods.

Chlorides↗

Specific traces in stun gun deployment.

Stun guns are electric shocking devices that can be deployed as defensive or offensive weapons. The aim of this study was the identification of several types of trace evidence for corroborating deployment and providing clues to the weapon actually used. In a series of some 250 tests, the after-effects of firing a stun gun were studied under the differential influence of factors, such as time duration, distance from target, and bare skin vs clothing as target surface. Examination with scanning electron microscopy (SEM) and energy dispersive X-ray spectrometer (EDS) demonstrated the presence of metallic deposits corresponding to the electrodes of the device used. The observed differences in the number of these pellets were related to the length of deployment in seconds and to the distance of the weapon from the target surface. Longer duration of firing was consistently associated with a larger number of metallic deposits. Elemental composition of the latter provided clues to the type of device used and its current status in terms of wear and tear. Further trace evidence we examined included craters on the target surface and their pattern of dissemination on human skin, textiles, and leather. It is concluded that the use of carbon tabs for examination with SEM/EDS offers a practicable method for collecting trace material following stun gun deployment. Important groups of trace evidence do exist, and their collection and examination appear feasible.

Clothing↗

Occupational relevance of positive standard patch-test results in employed persons with an initial report of an occupational skin disease.

OBJECTIVES: It is commonly accepted that the standard screening tray is an essential diagnostic test in patch testing supporting the diagnosis of contact dermatitis, the most common type of occupational skin disease (OSD). In this study standard patch-test results of employed persons with an initial report of an OSD were analyzed within 24 occupational groups. METHODS: An evaluation was made of employed persons recorded in the Register of Occupational Skin Diseases in Northern Bavaria (Berufskrankheitenregister Haut-Nordbayern; BKH-N) between 1990 and 1999, catering for those standard screening tray allergens tested over the 10-year period. RESULTS: Nickel sulfate was the most common sensitizer (29.5%), showing occupational relevance in only 11% of the cases sensitized. Other common sensitizers were cobalt chloride (13.5%), p-phenylenediamine free base (10.7%), potassium dichromate (9.8%), fragrance mix (5.4%), thiuram mix (4.2%), balsam of Peru (4.0%), chloromethylisothiazolinone/methylisothiazolinone (4.0%), and formaldehyde (4.0%). The most occupationally relevant sensitizers were thiuram mix (71%), epoxy resin (67%), p-phenylenediamine free base (59%), p-phenylenediamine-black-rubber mix/ N-isopropyl- N'-phenyl- p-phenylenediamine (53%), potassium dichromate (48%), formaldehyde (38%), chloromethylisothiazolinone/methylisothiazolinone (37%), and mercapto-mix/mercaptobenzothiazole (35%). Occupational groups at risk of acquiring delayed-type sensitization were, in particular, electroplaters, tile setters and terrazzo workers, construction and cement workers, solderers, wood processors, and leather and fur processors. CONCLUSIONS: The standard series contributes valuable information and asserts its position in clarifying the causes of OSDs. Based on the study results, the rate of occupationally relevant sensitization to each single allergen is demonstrated, and the difficulties in verifying the occupational relevance are discussed.

Adult↗

The effects of co-exposure to methyl ethyl ketone on the biological monitoring of occupational exposure to N,N-dimethylformamide.

OBJECTIVES: (1) To assess whether urinary N,N-dimethylformamide (U-DMF) is suitable as a biomarker when co-exposure to methyl ethyl ketone (MEK) exists, and to evaluate whether it is suitable as an exposure biomarker of DMF. (2) To examine whether the co-exposure to MEK affects the characteristics of U-NMF and U-DMF. (3) To investigate if the difference in creatinine-adjusted and non-adjusted measurements of urinary biomarkers of DMF exposure is substantial. METHODS: Personal exposure monitoring of N,N-dimethylformamide (DMF) and MEK on 11 synthetic-leather workers was performed for 5 consecutive days. Daily post-shift urine for each individual was collected and was analyzed for urinary N-methylformamide (U-NMF) and U-DMF levels on both non-adjusted and creatinine-adjusted bases. RESULTS: Both U-NMF and U-DMF showed significant associations with airborne DMF. Positive and significant associations between U-NMF and U-DMF on either a non-adjusted basis or a creatinine-adjusted basis were found. Satisfactory linear associations ( P<0.01) between all kinds of urinary biomarkers and DMF exposure were found. The co-exposure to MEK exerted more effect on the relationship of airborne DMF to U-DMF than to U-NMF. CONCLUSIONS: U-DMF is detectable when occupational DMF exposure is near or below the occupational exposure limit of 10 ppm. In view of the performance of sensitivity, specificity, and positive predictive value, U-NMF, in general, is superior to U-DMF. However, on a par with other findings in this and previous studies, U-DMF might be considered as a complimentary biomarker of exposure to DMF in addition to U-NMF. No distinction between creatinine-adjustment or non-adjustment for urine specimens was found in the biological monitoring of DMF exposure. Further exploration of the influence of co-exposure to MEK at higher exposure is warranted.

Butanones↗

Occupational exposure to n-hexane in Italy--analysis of a registry of biological monitoring.

OBJECTIVE: This study assesses 2,5-hexanedione (2,5-HD) in the urine of subjects exposed to n-hexane solvent between 1991 and 1998, from details obtained from the Registry of Biological Monitoring (BM) at the Florence Local Health Unit, and its development over time. METHODS: The Registry contains 15,925 samples from 6,650 subjects occupationally exposed to n-hexane, especially in leather (9,099 samples; 3,607 subjects) and shoe (3,865 samples; 1,938 subjects) production. RESULTS: Over the time span studied there was a total reduction of 31.9% in urinary 2,5-HD level. The yearly decrease over the entire period was 5.4%. Dividing the 8 years into three periods: before the introduction of the new legislation for health protection in the workplace (1991-1993), during its transition (1994-1996) and after its complete enforcement (1997-1998), respectively, we observed a marked decrease in the last period. Women and young people (under 30 years) experienced significantly higher absorption levels (respectively, 7.1% and 24.4%). CONCLUSION: The data suggest that monitoring was more frequent in subjects with higher starting values, and the greatest decrease was reported in this group. Reduction may be due to less n-hexane in the products used, better structural conditions in the factories, and the effectiveness of inspections carried out by the authority for hygiene and safety in the workplace. The results confirm the usefulness of the reporting of risk levels of exposure to industrial toxicants by routine biological monitoring.

Adolescent↗

Acute pulmonary toxicity following occupational exposure to a floor stain protector in the building industry in Switzerland.

BACKGROUND: Waterproofing agents are widely applied to leather and textile garments; they are also used as floor stain protectors by professionals. Acute respiratory injury is described in three cases of young healthy adults following occupational inhalation of a new waterproofing formulation containing an acrylate fluoropolymer. Within 1 or 2 h after exposure they developed a rapidly progressive dyspnoea; two of them had hypoxaemia and flu-like reactions. All patients improved with supportive treatment in a few days. The mechanism of toxicity is still under investigation, but experimental data suggest the role of this new acrylate fluoropolymer. CONCLUSION: Tilers should be warned against spraying floor stain repellents; there is also a need to make consumers aware that the spraying of waterproofing agents in a closed environment and concomitant smoking should be avoided.

Acrylic Resins↗

Biological monitoring of occupational exposure to N,N-dimethylformamide--the effects of co-exposure to toluene or dermal exposure.

OBJECTIVES: The objective of this study is to assess the exposure and intake dose of N,N-dimethylformamide (DMF) and the correlation between them, according to the type of exposure for the workers in the DMF industry. METHODS: We monitored 345 workers occupationally exposed to DMF, from 15 workshops in the synthetic fiber, fiber coating, synthetic leather and paint manufacturing industries. Ambient monitoring was carried out with personal samplers to monitor the external exposure. Biological monitoring was done to determine the internal dose by analyzing N-methylformamide (NMF) in end-shift urine. Work procedure and exposure type of each DMF workshop was carefully surveyed, to classify workers by exposure type according to work details. Workers were classified into three groups (Group A: continuous and direct exposure through inhalation and skin; Group B: intermittent and short-term exposure through inhalation and skin; Group C: continuous and indirect exposure mostly through inhalation). RESULTS: Geometric mean of DMF concentration in air was 2.62 (GSD 5.30) ppm and that of NMF in urine was 14.50 (GSD 3.89) mg/l. In the case of continuous absorption through inhalation and dermal exposure (Group A), the value of NMF in urine corresponding to 10 ppm of DMF was 45.3 mg/l (r = 0.524, n = 178), 39.1 mg/g creatinine (r = 0.424), while it was 37.7 mg/l (r = 0.788, n = 37), 24.2 mg/g creatinine (r = 0.743) in the case of absorption mostly through inhalation (Group C). Creatinine correction reduced the correlation between two parameters. CONCLUSION: The NMF in urine corresponding to 10 ppm DMF, of the dermal and inhalation exposure group was 39.1 mg/g creatinine (r = 0.424, n = 178), while that of the inhalation exposure-only group was 24.2 mg/g creatinine (r = 0.743, n = 37). Co-exposure with toluene reduced the NMF excretion in urine.

Air Pollutants↗

Biological monitoring of occupational exposure to cyclohexane by urinary 1,2- and 1,4-cyclohexanediol determination.

OBJECTIVES: This article reports the results obtained with the biological and environmental monitoring of occupational exposure to cyclohexane using 1,2-cyclohexanediol (1,2-DIOL) and 1,4-DIOL in urine. The kinetic profile of 1,2-DIOL in urine suggested by a physiologically based pharmacokinetic (PBPK) model was compared with the results obtained in workers. METHODS: Individual exposure to cyclohexane was measured in 156 workers employed in shoe and leather factories. The biological monitoring of cyclohexane exposure was done by measurement of 1,2-DIOL and 1,4-DIOL in urine collected on different days of the working week. In all, 29 workers provided urine samples on Monday (before and after the work shift) and 47 workers provided biological samples on Thursday at the end of the shift and on Friday morning. Another 86 workers provided biological samples at the end of the work shift only on Monday or Thursday. RESULTS: Individual exposure to cyclohexane ranged from 7 to 617 mg/ m3 (geometric mean value 60 mg/m3). Urinary concentrations of 1,2-DIOL (geometric mean) were 3.1, 7.6, 13.2, and 6.3 mg/g creatinine on Monday (pre- and postshift), Thursday (postshift) and Friday (pre-shift), respectively. The corresponding values recorded for 1,4-DIOL were 2.8, 5.1, 7.8, and 3.7 mg/g creatinine. A fairly close, statistically significant correlation was found between environmental exposure to cyclohexane and postshift urinary 1,2-DIOL and 1,4-DIOL on Monday. Data collected on Thursday and Friday showed only a poor correlation to exposure with a wide scatter. Both metabolites have a urinary half-life of close to 18 h and accumulate during the working week. CONCLUSIONS: Comparison between data obtained from a PBPK model and those found in workers suggests that 1,2-DIOL and 1,4-DIOL are urinary metabolites suitable for the biological monitoring of industrial exposure to cyclohexane.

Cyclohexanes↗

Bubo masquerading as an incarcerated inguinal hernia.

A 44-year old, male, tattooed, leather jacket clad, Harley-Davidson motorcyclist arrived at the emergency room with a tender, irreducible mass, presenting at the external inguinal ring. In 1998, lung biopsy was read as miliary granuloma. No herniation was found on urgent preperitoneal exploration. Incision of the mass showed acid-fast bacilli. Culture later revealed Mycobacterium avium-intracellulare (MAI). A blood count showed CD4 lymphopenia; HIV was negative and remains so 2 years later.

Adult↗

Co-composting of hair waste from the tanning industry with de-inking and municipal wastewater sludges.

Production of waste hair in the leather manufacturing industry is increasing every year due to the adoption of hair-save unhairing techniques, leaving the tanners with the problem of coping with yet another solid by-product. Numerous potential strategies for hair utilisation have been proposed. However, the use of hair waste as agricultural fertiliser is one of its most promising applications due to the high nitrogen content of hair. Agricultural value of hair can be increased by composting. This paper deals with the composting of hair from the unhairing of bovine hide. Results indicated that hair cannot be either composted on its own or co-composted with de-inking sludge, a chemical complementary co-substrate. However, good results were obtained when co-composted with raw sludge from a municipal wastewater treatment plant at hair:raw sludge weight ratios 1:1, 1:2 and, 1:4 in lab scale and pilot plant scale composters. In all cases, a more stable product was achieved at the end of the process. Composting in the pilot plant composter was effectively monitored using Static Respiration Indices determined at process temperature at sampling (SRI(T)) and at 37 degrees C (SRI(37)). Notably, SRI(T) values were more sensitive to changes in the biological activity. In contrast, Respiratory Quotient (RQ) values were not adequate to follow the development of the process.

Agriculture↗

Effects of commonly used mitogens on the cytotoxicity of 4-tertiary butylphenol to human melanocytes.

In the search for environmental compounds responsible for contact or occupational vitiligo, it was found that the most potent was 4-tertiary butylphenol (4-TBP). Exposure to 4-TBP is widespread both in industry and in consumer items including synthetic leather, plastic, glues, and germicidal phenolic detergents. How 4-TBP causes depigmentation and the death of melanocytes is currently unclear. Growth mitogens for human melanocytes include alpha-melanocyte stimulating hormone (alpha-MSH), basic fibroblast growth factor (bFGF) and 12-o-tetradecanoylphorbol-13-acetate (TPA). The former two mitogens are physiological growth factors for melanocytes. We have studied the effects of these mitogens on the cytotoxicity of 4-TBP in human melanocytes. Our results demonstrated that deprivation of alpha-MSH or bFGF from melanocyte cultures resulted in reduced cytotoxicity to 4-TBP. Similar results were obtained upon treatment of melanocytes with an inhibitor of cAMP-dependent protein kinase A (PKA), that is known to be activated by alpha-MSH, or with an inhibitor of the tyrosine kinase bFGF receptor. In contrast, removal of fetal bovine serum or TPA from the culture medium did not influence the susceptibility of melanocytes to 4-TBP. These results suggest that activation of the cAMP and tyrosine kinase signaling pathways, both of which are involved in the mitogenic response of melanocytes, increase the susceptibility of these cells to the cytotoxic effects of 4-TBP.

Animals↗

Gene Cloning, Expression, and Purification of Kunitz Trypsin Inhibitor from Glycine max Using Halo Tag.

Soybean Kunitz Trypsin Inhibitor (SKTI) is one of the most extensively studied protease inhibitors, with applications in pest management, medicine, the food processing industry, and the leather industry. In this study, SKTI was cloned into the pFN29A Flexi vector containing a barnase gene. Genomic DNA was isolated from tender soybean leaves, and SKTI was amplified by PCR to obtain a 671&#xa0;bp product. After cloning, an internal 380&#xa0;bp sequence was amplified using specific primers to confirm that the cloned sequence was a functional SKTI, as non-functional SKTI genes also exist in Glycine max. The amplified PCR product, containing an AsiSI site at the 5' end and a PmeI site at the 3' end, was cloned into the pFN29A vector. The resulting colonies were screened by colony PCR, and the insert sequence was confirmed by Sanger sequencing. The recombinant protein, containing a His-tag, Halo-tag, and a TEV protease cleavage site, was expressed in Escherichia coli BL21 cells. Maximum expression was achieved 5&#xa0;h after induction with 0.5&#xa0;mM IPTG at 37&#xa0;&#xb0;C. The expressed SKTI was purified using affinity chromatography on HaloLink resin, and the bound SKTI was cleaved with HaloTEV protease to obtain pure SKTI. The purified inhibitor effectively inhibited bovine trypsin, with an IC&#x2085;&#x2080; of 0.6&#x2009;&#xb1;&#x2009;0.003&#xa0;&#xb5;g/&#xb5;l, yielding 1.6&#xa0;mg per gram of bacterial pellet. The 24&#xa0;kDa inhibitor remained stable up to a temperature of 50&#xa0;&#xb0;C. Kinetic analysis revealed that recombinant SKTI competitively inhibits trypsin, with a K&#x1d62; value of 14&#xa0;&#xb5;M.

Cloning, Molecular↗

Distal in situ saphenous vein grafts for limb salvage. Increased operative blood flow and postoperative patency.

Early failure remains a major obstacle to successful distal bypass surgery using vein grafts for limb salvage. Thirty distal bypass graft procedures were performed for limb salvage using the in situ technique. Grafts were anastomosed to the distal popliteal artery in 13 patients and to the infrapopliteal artery in 17 patients. Sixteen patients had inadequate saphenous veins for reversed vein grafts. The mean blood flow measured through these grafts (n = 20) was 164 +/- 22 ml/min and increased to 278 +/- 31 ml/min after administration of 30 mg of papaverine. All grafts were patent at the time of hospital discharge and patients were followed for 1 to 28 months. Life table analysis of the 30 procedures shows a patency of 100 percent at 18 months follow-up. One graft subsequently failed at 22 months. Long-term limb salvage was achieved in 100 percent of the patients in this series. The excellent blood flow through these grafts suggests that the in situ vein graft technique may be more favorable for arterial reconstruction than the reversed vein graft technique. Our preliminary data confirm the observations of Leather et al [3,4], that the rates of vein utilization and graft patency are higher with the in situ technique.

Adult↗

Evolution of the in situ bypass.

The origins of the in situ vein bypass in Montreal, Canada and in London, England, are described. The subsequent evolution of the original techniques in Europe and the United States are followed. The condemnation of the procedure in the United States in 1969 is noted. The persistence of Cartier in Montreal and Hall in Norway and the revival of interest in the procedure by Leather and Karmody in Albany, New York, is recounted. The pathophysiologic basis for the complications of the method are analyzed and the measures by which they are currently remedied are shown. The method's present superiority is reported. The initial rejection and slow acceptance of this method is explained in terms of the special conditions attendant on its introduction and the attitudes of surgeons to new procedures.

Canada↗

Influence of shoes and heel strike on the loading of the hip joint.

The forces and moments acting at the hip joint influence the long-term stability of the fixation of endoprostheses and the course of coxarthrosis. These loads may depend on the kind of footwear and the walking or running style. These factors were investigated in a patient with instrumented hip implants. He wore different sports shoes, normal leather shoes, hiking boots and clogs and walked barefoot with soft, normal and hard heel strikes. The loads were lowest while walking and jogging without shoes. All shoes increased the joint force and the bending moment at the implant slightly but the torsional moment rose by up to 50%. No relation was found between the different type of shoes and the load increase, only shoes with very hard soles were clearly disadvantageous. Soft heels, soles or insoles did not offer advantages. Gait stability seems to play the most important role in increasing the joint loading and should be the criterion for the choice of footwear. Smooth gait patterns with soft heel strikes are the only means to reduce joint loading during slow jogging.

Aged↗

Valvular obstruction of blood flow through saphenous veins.

To measure effects of vein valves upon blood flow through venous bypass conduits, 15 human saphenous veins (mean length 40.6 cm, 5.3 valves/vein) were perfused with normal saline at constant pressure (100 mm Hg). Flow through vein was measured before and after valve bisection. Vein valves were bisected using Leather's techniques. After valve bisection, flow in antegrade and retrograde directions was measured in seven veins. These data were analyzed using paired t tests. Antegrade flow through seven veins with intact valves averaged 317.1 cc/min. With valve bisection this increased significantly (P less than 0.001) to 474.3 cc/min. Retrograde flow through veins with valves bisected increased significantly (P less than 0.0001) to 428.3 cc/min. Eleven veins (mean length 42.2 cm, 5.6 valves/vein) perfused simulated capillary beds with banked blood using pulsatile flow (mean pressure 92 mm Hg). Flow, again, was measured before and after valve bisection. Data were analyzed using the paired t test. Antegrade flow increased from 124.4 cc/min in veins with valves intact to 142.5 cc/min once valves were bisected (P = 0.02). These data demonstrate that saphenous vein valves cause significant obstruction to blood flow under conditions similar to those in the arterial system. Bisection of vein valves significantly increases flow through vein. Improved patency of vein grafts using valve bisection techniques may be explained by increased blood flow alone.

Blood Flow Velocity↗

Accommodation, refractive error and eye growth in chickens.

We raised chickens with defocusing lenses of differing powers in front of their eyes. For this purpose, small hoods made from soft, thin leather were carefully fitted to their heads. Lenses were attached to the hoods by velcro fasteners and could be easily removed for cleaning. The powers of the lenses were such that their optical effects could be compensated for by accommodation. It was verified by infrared (IR) photoretinoscopy that the chickens could keep their retinal images in focus. Wearing a lens resulted in a consistent shift of the non cycloplegic refractive state (measured without the lens) which was in the direction to compensate for the lens. We used a sensitive technique (precision = +/- 50 micron as estimated from the variability of repeated measurements) to measure the posterior nodal distance (PND) in excised eyes of birds grown with lenses. The PND, in turn, was used to compare eyes treated with different lenses. It was found that the PND was increased in eyes which were treated with negative lenses compared to those treated with positive lenses. This effect occurs independently in both eyes and it is not due to changes in corneal curvature. We discuss our result in terms of a closed-loop feedback system for the regulation of eye growth.

Accommodation, Ocular↗

Human health perspectives on environmental exposure to benzidine: a review.

Benzidine, an odorless, white to slightly reddish-white crystalline organic compound, is an environmental contaminant that has been identified at about 30 National Priorities List (NPL) hazardous waste sites in the United States. In the environment, it is usually found attached to suspended particles either in its "free" state or as chloride or sulfate salts. In the past, U.S. industries used large quantities of benzidine to produce dyes for paper, clothes, and leather. Since the ban on its production and use in the United States in the 1970s, this compound is imported for specialty uses. People living near hazardous waste sites might be exposed to benzidine by drinking contaminated water, by inhaling contaminated air, or by swallowing or touching contaminated dust. People can also be exposed by using benzidine dyes on paper, clothes, and other materials. Human occupational data and studies of laboratory animals suggest that people exposed to benzidine may develop adverse systemic health effects or cancer. The U.S. Environmental Protection Agency (EPA), the U.S. Department of Health and Human Services, the International Agency for Research on Cancer (IARC), and the World Health Organization (WHO) have classified benzidine as a carcinogen. Urinary bladder cancer is the most common form of cancer caused by exposure to benzidine. The stomach, kidneys, brain, mouth, esophagus, liver, and gallbladder might also be targets. The information presented in the article may help public health officials, physicians, and toxicologists evaluate and develop the health information materials on the nature of benzidine in the environment and its potential impact on public health.

Animals↗