Female Wistar rats were exposed to 4 g m-3 unleaded petrol for 8 h a day, 5 days a week for 60 days. Urinary beta 2-microglobulin (beta 2-m), lactate dehydrogenase (LDH) and lysozyme were used as markers of tubular dysfunction. Urinary excretion of albumin and the glomerular filtration rate (GFR) were used as indicators of glomerular impairment. There were no statistically significant changes in the GFR or urinary albumin concentrations in the exposed group. Petrol exposure induced an increase of beta 2-m, total proteins, lysozyme and LDH excretion, but only beta 2-m was increased significantly. Our results show that subchronic exposure to high levels of unleaded petrol induced only a mild proximal tubular dysfunction in female rats.

Animals↗

PubMedDate not supplied

Assessment of molybdenum toxicity in humans.

In an attempt to define a tolerable daily intake (TDI) for molybdenum based on a toxicological risk analysis approach, a large literature survey was conducted. In man, absorption of molybdenum after oral intake is in the range of 28-77% and urinary excretion is 17-80% of the total dose. A low order of toxicity of molybdenum compounds has been observed in humans. However, with the available data, it is not possible to calculate any dose-response or dose-effect relationships. Because molybdenum toxicity is associated with copper intake or depleted copper stores in the body, humans who have an inadequate intake of dietary copper or some dysfunction in their copper metabolism that makes them copper-deficient could be at greater risk of molybdenum toxicity. In the absence of relevant human studies, animal studies were evaluated for the derivation of the TDI. Effects of Mo on reproduction and foetal development were found to be critical effects observed in rats and mice. A dose-response relationship was observed in a study by Fungwe et al., with a 'no observed adverse effect' level (NOAEL) and a 'lowest observed adverse effect' level (LOAEL) of 0.9 and 1.6 mg Mo kg(-1) day(-1), respectively. Applying uncertainty factors of 10 for intraspecies and 10 for interspecies differences to the NOAEL, a TDI of 0.009 mg Mo kg(-1) day(-1) was calculated. The TDI is given a medium confidence rating. This TDI is more than double the upper limit of adequate intake for adolescents and adults that was derived from the Mo content of the average diet in the USA.

Absorption↗

PubMedDate not supplied

Kidney function in male and female rats chronically exposed to potassium dichromate.

Male and female Wistar rats were given 25 mg l-1 chromium (as potassium dichromate) in drinking water for 6 months. Lactate dehydrogenase, lysozyme, total proteins, N-acetyl-beta-D-glucosaminidase, albumin and beta 2-microglobulin (beta 2-m) were measured in 24-h urine after 3 and 6 months of exposure. Body and kidney weight and chromium excretion were also examined. Except for the chromium excretion, no statistically significant changes were observed in the exposed male rats. In female rats there were significant increases in the urinary excretion of albumin after 3 and 6 months of exposure and the urinary excretion of beta 2-m after 3 months of exposure.

Animals↗

PubMedDate not supplied

Renal alterations in female rats following subchronic lead exposure.

Female Wistar rats were given 1% or 0.1% lead acetate in drinking water for 2 or 4 months, respectively. Urinary beta 2-microglobulin, N-acetyl-beta-D-glucosaminidase, lactate dehydrogenase and lysozyme were used as markers of tubular dysfunction. Excretion of albumin and glomerular filtration rate were used as indicators of glomerular impairment. Kidney and body weights and morphological changes in the kidney were also studied. Exposure to 1% lead acetate induced a mean blood lead level of 1730 micrograms l-1 and caused only an increase of beta 2-microglobulin excretion and relative kidney weight. Light microscopy of kidney revealed morphological changes mainly in the epithelial cells of the proximal tubules. The role of acetate or reduced water intake on kidney function was excluded because 1% sodium acetate or the restriction of water intake to the volume consumed by the rats of the lead-exposed group was ineffective. Exposure to 0.1% lead acetate induced a blood lead level of 376 micrograms l-1, corresponding to the current level in industry workers, without any sign of nephrotoxicity. Comparison of this study with the results of a previous study on male rats indicates no sex difference in the nephrotoxicity of lead.

Animals↗

PubMedDate not supplied

Effect of prenatal and postnatal exposure to lead on kidney function in male and female rats.

The effect of 5 months' exposure to 0.5% lead acetate in drinking water on the kidney function of developing rats was studied. In both sexes, lead exposure produced a significant elevation of the kidney weight and after 3 months' treatment both male and female rats showed signs of tubular impairment. In male rats increased beta 2-microglobulin and lactate dehydrogenase excretion was observed. Lysozyme was increased after 5 months of exposure. No changes were observed in total proteins and albumin excretion. Female rats showed a significantly increased excretion of beta 2-microglobulin from 3 months onwards, while lactate dehydrogenase increased only at the end of 3 months and total proteins after 5 months of exposure. No changes were observed in lysozyme and albumin excretion. Thus, the results suggest that lead exposure produces changes in the renal tubular function of developing rat. There is no sex difference in the nephrotoxicity of lead. Comparison with our previous studies suggests that exposure to lead starting at weaning is more renotoxic than exposure starting 2 months later. However, prenatal exposure might also have been a contributory factor.

Albuminuria↗

PubMedDate not supplied

Adjustment of permissible exposure values to unusual work schedules.

Research activities sought development of a method to adjust exposure limits for 694 substances for unusual work schedules. A consensus was established on the basic toxicological principle for adjustment; criteria for adjustment were selected by a panel of scientists coordinated by a committee of international experts and supported by toxicokinetic modeling; and a group of toxicologists attributed primary health effects and related adjustment category to each substance. A consensus among scientists and employers' and workers' representatives was established on the protocol of the application, in the field, of the adjusted exposure limits. The guiding toxicological principle for adjusting exposure standards to unusual work schedules is to guarantee an equivalent degree of protection for workers with unusual schedules as for workers with a conventional schedule of 8 hours per day, 5 days per week. The process of the adjustment is inspired from the Occupational Safety and Health Administration logic for attribution of primary health effects and adjustment categories ranging from no adjustment to daily or weekly adjustments. The adjusted exposure limits are calculated according to Haber's rule. Decisions on attribution of adjustment categories for the following toxicological effects were reached: respiratory sensitizers (asthma); skin sensitizers; tissue irritants versus tissue toxicants; methemoglobinenia-causing agents; cholinesterase inhibitors; and reproductive system toxicants and teratogens. A simple procedure is presented to facilitate the calculation, application, and interpretation of the adjusted exposure limits.

Guideline Adherence↗