The German view: effects of nitrogen dioxide on human health--derivation of health-related short-term and long-term values.

The presented overview concerning health relevant effects caused by nitrogen dioxide (NO2) resumes the current state of results from animal experiments and human studies (epidemiology and short-term chambers studies). NO2 concentrations applied in animal experiments were mostly considerably higher than in ambient air. Therefore, short- and long-term limit values were derived from human data. Experimental studies conducted with humans demonstrate effects after short-term exposure to concentrations at or above 400 microg NO2/m3. Effects on patients with light asthma could not be observed after short-term exposure to concentrations below 200 microg/m3. On basis of epidemiological long-term studies a threshold below which no effect on human health is expected could not be specified. Two short-term limit values have been proposed to protect public health: a 1-h value of 100 microg/m3 and a 24-h mean value of 50 microg/m3. Due to the limitations of epidemiological studies to disentangle effects of single pollutants, a long-term limit value cannot be easily derived. However, applying the precautionary principle, it is desirable to adopt an annual mean of 20 microg NO2/m3 as a long-term mean standard to protect public health.

Nephrotoxicity of organic solvents: biomarkers for early detection.

OBJECTIVES: Evidence for a relationship between chronic kidney diseases or progression of already existing diseases (glomerulonephritides) and occupational solvent exposure has been found in case reports, in case-control studies and also in cross-sectional studies. An analysis of the available literature was performed with respect to markers measured in cross-sectional studies that might be useful for an early detection of solvent-induced effects on the kidney. METHODS: The relevant cross-sectional studies were evaluated and the following markers were analyzed with respect to their suitability as biomarker for renal damage: total protein, albumin, transferrin, IgG, beta(2)-microglobulin, retinol-binding protein, N-acetyl-beta-D: -glucosaminidase, alanine aminopeptidase, beta-galactosidase, beta-glucuronidase, leucin aminopeptidase, alkaline phosphatase, lysozyme, Tamm-Horsfall protein and laminin fragments in urine as well as E-selectin, laminin and anti-laminin antibodies and anti-glomerular basement membrane antibodies in serum. RESULTS: An increased albumin excretion was observed more frequently in groups of workers exposed to various solvents (like toluene, styrene, aliphatic/aromatic hydrocarbon mixtures, tetrachloroethene, mixtures of chlorinated hydrocarbons) than in controls. No clear pattern emerged for the other markers. CONCLUSIONS: The determination of albumin excretion in the urine appears to be a useful parameter for monitoring solvent-exposed workers.

[Primary cultures of rat hepatocytes on microcarriers as a metabolising system in toxicity testing in cell cultures]

The toxicity of many chemicals is modified by biotransformation reactions in the liver. To detect metabolism-mediated alterations of the cytotoxicity of chemicals in vitro, a coculture system consisting of rat hepatocytes on collagen-coated microcarriers and "monolayers" of BALB/c3T3 cells was developed. This cocultivation system was used to study toxic effects of three model compounds, i.e. cyclophosphamide, allyl alcohol and ethylene glycol, respectively. Cytotoxicity to 3T3 cells for each compound increased in cocultures with hepatocytes. The parallel assessment of toxicity to both cell types in coculture and to cultures of 3T3 cells revealed qualitatively as well as quantitatively different toxic effects of these substances. The results indicate that cocultivation of microcarrier-attached hepatocytes with target cells could represent valuable tool to study effects of biotransformation on the toxicity of xenobiotics in vitro.