New insight into solvent-related end-stage renal disease: occupations, products and types of solvents at risk.

OBJECTIVES: It has been shown that all-solvent exposure is associated with the progression of primary glomerulonephritis to end-stage renal disease (ESRD), but little is known about the type of solvents that are high risk. The aim of this study was to investigate the role of solvents by occupation, product and type. METHODS: Using a retrospective cohort design, the authors studied 269 patients with non-end-stage and biopsy-proven primary glomerulonephritis diagnosed between 1994 and 2001 in Paris and its suburbs. Two industrial hygienists evaluated patients' exposures from lifetime occupational histories collected by interview from 2002-4, and using a list of the 30 most common solvents. The studied outcome was ESRD, defined as glomerular filtration rate <15 ml/mn/1.73 m(2) or dialysis. It was recorded during a mean follow-up of five years. Cox models were used to estimate adjusted hazard ratios (HR) of ESRD related to exposures. RESULTS: Eighteen per cent of the patients had ever been exposed to solvents. Those with the highest risk of progression to ESRD were exposed machinery fitters and machine assemblers (HR 4.7, 95% CI 1.2 to 17.4) and plumbers/welders (HR 4.2, 95% CI 1.3 to 13.6), as compared to never exposed patients, as well as those who ever handled printing inks and petroleum products (HR 12.6 (95% CI 1.7 to 94.9) and 3.2 (95% CI 1.4 to 7.2), respectively). Among solvents, the highest risks were found for: toluene/xylene (HR 5.1, 95% CI 1.8 to 14.8), gasoline, fuel and gas-oil (HR 8.6, 95% CI 2.7 to 27.4), and ketones (HR 13.3, 95% CI 1.4 to 123.5). CONCLUSION: This study highlights the potential nephrotoxicity of several solvents. Intervention to promote screening for proteinuria in exposed workers may prevent the progression of glomerulonephritis to ESRD.

Comparison of direct (X-ray diffraction and infrared spectrophotometry) and indirect (infrared spectrophotometry) methods for the analysis of alpha-quartz in airborne dusts.

In this study, the alpha-quartz contents measured by different analytical techniques (X-ray diffraction, direct method; and infrared spectrophotometry, direct and indirect methods) were compared. The analyses were carried out on filters sampled in an industrial setting by means of a Dorr-Oliver cyclone. To verify the methodology used, filters loaded with pure alpha-quartz were also analysed. By and large, the agreement between the two direct methods was close on average, but on the basis of a comparison of the individual results, considerable differences exist. In absolute value, the mean relative deviation between the two techniques was <25% in only 47.8% of the cases. The results obtained by the indirect method (infrared) were on average 13% lower than the results obtained by the two direct methods with a more important difference (23%) for samples where calcite was identified by X-ray diffraction in comparison with those where it was not (8%). This underestimation, which was not owing to dust losses during preparation, is probably explained by the elimination of organic compounds during dust calcinations or by the transformation of mineral compounds. The indirect method introduces additional sample handling operations with more risk of material loss. When the quantity of calcined material was <0.4 mg, the weighing operations necessary to correct any losses of material resulted in considerable variability. In terms of overall uncertainty, it would be better in this case not to carry out correction and to employ an operating mode favouring the recovery of a maximum of material while accepting a bias of about 5-7%.

Comparison by X-ray diffraction and infrared spectroscopy of two samples of alpha quartz with the NIST SRM 1878a alpha quartz.

The aim of this study was to compare the X-ray diffraction and infrared spectrophotometric patterns of two samples of alpha quartz (QUIN1 and QUIN2) with that of NIST SRM 1878a alpha quartz certified 100% crystalline. As it is known that the intensity diffracted and the absorbance per mass unit for a given type of alpha quartz depend on its particle size, this factor was taken into account. To do this, different types of alpha quartz were sampled on filters using a Dorr-Oliver cyclone to select particle size. Variation in the flow rate of the cyclone in the range 1.2-2.8 l/min allowed the volume median diameter of the sampled particles to be varied. For the four strongest diffraction lines it was observed that the intensity per mass unit increased with the volume median diameter of the particles. For infrared spectrophotometry for analytical band wavelengths close to 12.5 micro m, it was observed that the absorbance per mass unit decreased as particle size increased. The opposite effect was noted for analytical band wavelengths >14.4 micro m. Compared with SRM 1878a alpha quartz, certified 100% crystalline, the purity of QUIN1 alpha quartz was 93.1% (confidence interval 92.4-93.8%) when measured by X-ray diffraction and 91.5% (confidence interval 90.1-92.9%) when measured by infrared spectrophotometry. In the case of QUIN2 alpha quartz the purity was globally lower.

Relative developmental toxicities of acrylates in rats following inhalation exposure.

The developmental toxicities of seven acrylates were studied in Sprague-Dawley rats after inhalation exposure for 6 h/day, during days 6 to 20 of gestation. The exposure concentrations were: for acrylic acid, 50, 100, 200, or 300 ppm; for methyl acrylate, 25, 50, or 100 ppm; for ethyl acrylate, 25, 50, 100, or 200 ppm; for butyl acrylate, 100, 200, or 300 ppm; for ethylhexyl acrylate, 50, 75, or 100 ppm; for hydroxyethyl acrylate, 1, 5, or 10 ppm; and for hydroxypropyl acrylate, 1, 5, or 10 ppm. No treatment-related increases in embryo/fetal mortality or fetal malformations were observed after exposure to any of these acrylates. Fetal toxicity, indicated by reduced fetal body weight, was observed after exposure to 300 ppm acrylic acid, 100 ppm methyl acrylate, 200 ppm ethyl acrylate, and 200 or 300 ppm butyl acrylate in the presence of overt signs of maternal toxicity. While there was evidence of maternal toxicity, no significant developmental toxic effects were observed after exposure to ethylhexyl acrylate, hydroxyethyl acrylate, or hydroxypropyl acrylate at any concentration. These results indicate that inhaled acrylic acid, methyl acrylate, ethyl acrylate, butyl acrylate, ethylhexyl acrylate, hydroxyethyl acrylate, and hydroxypropyl acrylate are not selectively toxic to the embryo or fetus.

Assessment of exposure to carcinogenic N-nitrosamines in the rubber industry.

Exposures to volatile nitrosamines were measured at 24 rubber manufacturing plants from 1992 to 1995. A total of 709 exposure measurements were taken in general areas or personal breathing zones to estimate exposure according to production types (seals, joints, tyres, gloves, etc.) and production steps, from mixing to storage. Five different nitrosamines were identified. N-Nitrosodimethylamine is the most frequently encountered nitrosamine and represents the most important fraction of the total nitrosamine concentration measured in a given sample. This fact is consistent with the use of rubber additives containing corresponding amine precursors. One hundred and forty-one of the 709 values exceeded the German target value (TRK) of 2.5 micrograms/m3 for all nitrosamines present from rubber vulcanisation, the only available standard for occupational nitrosamine exposures. The salt bath curing process generates particularly high nitrosamine levels, 90% of the 96 measurements being over the TRK, with many values exceeding 20 micrograms/m3. The reasons why the TRK is exceeded are generally well identified. To reduce nitrosamine emission levels it would be advisable to eliminate nitrogen oxide sources, principally by using a process other than salt bath curing, and to develop different rubber stocks that do not contain secondary aliphatic amine functional groups ("safe amines").

Developmental toxicity of inhaled ethylene oxide in rats following short-duration exposure.

The developmental toxicity of ethylene oxide (EtO) was examined in Sprague-Dawley rats following inhalation exposure during Days 6 to 15 of gestation. Two different exposure regimens were used: (1) exposure for 0.5 hr once a day to 0, 400, 800, or 1200 ppm EtO; or (2) exposure for 0.5 hr three times a day to 0, 200, or 400 ppm EtO or 0, 800, or 1200 ppm EtO. Repeated brief exposures (3 x 0.5 hr/day) to EtO caused fetal toxicity indicated by reduced fetal weight at 800 and 1200 ppm, and overt maternal toxicity manifested as reduced body weight gain at 1200 ppm. Neither embryolethality nor teratogenicity occurred following any exposure regimen.

[Glomerular nephropathies and exposure to organic solvents--a case-control study]. / Néphropathies glomérulaires et exposition aux solvants organiques-- Etude cas-témoins.

Several studies have suggested that exposure to organic solvents is associated with glomerular nephropathies (GN), but this relationship remains controversial. A case-control study of 298 biopsy-proven cases and 298 hospital controls, matched for year of birth, sex, origin, and place of residence, was conducted between 1989 and 1991 in five hospitals in the Paris area : 82 cases of membranous glomerulopathy were included ; 100, nephrotic syndrome with either minimal change nephropathy or focal and segmental hyalinosis (MCN/FSH); and 116, IgA nephropathy (IgA N). Subjects were interviewed about their lifelong occupational and non-occupational activities. Type, level, and duration of solvent exposure were assessed blind with respect to case-control status by two industrial hygienists. HLA phenotypes were determined. Among males, a clear association, which was not explained by social class, was observed between chronic renal failure and high exposure to solvents for both MCN/FSH (OR = 7.7, 95% CI 1.4-41.6) and IgA N (OR = 3.5, 95% CI 1.0-11.8). The odds ratios increased with duration of exposure. No relationship was observed between such exposure and GN cases with normal renal function. No evidence was found that the HLA phenotype plays a role in the solvent exposure-disease association. These results support the hypothesis of a causal relationship between high solvent exposure, which concerned 15% of the males in this study, and the development of GN with chronic renal failure.

Organic solvent exposure may increase the risk of glomerular nephropathies with chronic renal failure.

BACKGROUND: Several studies have suggested that exposure to organic solvents is associated with glomerular nephropathies (GN), but this relationship remains controversial. METHODS: A case-control study of 298 biopsy-proven cases and 298 hospital controls, matched for year of birth, sex, origin, and place of residence, was conducted between 1989 and 1991 in five hospitals in the Paris area: 82 cases of membranous glomerulopathy were included; 100, nephrotic syndrome with either minimal change nephropathy or focal and segmental hyalinosis (MCN/FSH); and 116, IgA nephropathy (IgA N). Subjects were interviewed about their lifelong occupational and non-occupational activities. A 'blind' assessment of type, level, and duration of solvent exposure was carried out by two industrial hygienists. Human leucocyte antigen (HLA) phenotypes were determined. RESULTS: Among males, a clear association, which was not explained by social class, was observed between chronic renal failure and high exposure to solvents for both MCN/FSH (OR = 7.7, 95% CI: 1.4-41.6) and IgA N (OR = 3.5, 95% CI: 1.0-11.8). The odds ratios increased with duration of exposure. No relationship was observed between such exposure and GN cases with normal renal function. No evidence was found that the HLA phenotype plays a role in the association between solvent exposure and the disease. CONCLUSIONS: These results support the hypothesis of a causal relationship between high solvent exposure, which concerned 15% of the males in this study, and the development of GN with chronic renal failure.

Transient non-cardiogenic pulmonary edema following massive ingestion of ethylene glycol butyl ether.

A case of acute poisoning with ethylene glycol butyl ether (EGBE) is reported in a chronic alcohol abuser. On admission the 53-year-old patient was comatose with metabolic acidosis, shock, and noncardiogenic pulmonary edema confirmed by haemodynamic study. Following supportive treatment and haemodialysis the outcome was favorable. The relationship between respiratory failure and EGBE is examined.

Testing natural indigo for genotoxicity.

The genotoxicity of indigo has been assessed by two short-term tests. The mutagenicity of natural indigo was compared with that of synthetic indigo. Both chemicals were tested using the standard procedure of the Salmonella/microsome mutagenicity test as described by Ames. The substance exhibits mutagenicity towards strains TA1538 and TA98 when S9 preparations of rat liver induced with Aroclor 1254 were present in the medium. The clastogenic potential was evaluated by the micronucleus test in the bone marrow of male mice. The test compound was administered twice with an interval of 24 h, the animals were killed 30 h and 54 h after the first treatment. When the test compound was given by oral gavage as two equal dosages of 0.1, 1 and 1.2 g/kg body weight, no statistically significant increase in the percentage of polychromatic erythrocytes with micronuclei was observed for any group treated with natural indigo.