Inhibition of multidrug resistance proteins MRP1 and MRP2 by a series of α,β-unsaturated carbonyl compounds

To study the possible interplay between glutathione metabolism of and MRP inhibition by thiol reactive compounds, the interactions of a series of α,β-unsaturated carbonyl compounds with multidrug resistance proteins 1 and 2 (MRP1/ABCC1 and MRP2/ABCC2) were studied. α,β-Unsaturated carbonyl compounds react with glutathione, and therefore either...

Glutathione depletion in rat hepatocytes: A mixture toxicity study with alpha,ß-unsaturated esters

Glutathione (GSH) depletion is often reported as an early cytotoxic effect, caused by many reactive organic chemicals. In the present study, GSH depletion in primary rat hepatocytes was used as an in vitro effect-equivalent to measure the toxic potency of α,β-unsaturated esters (acrylates and methacrylates). 2. When these compounds were...

Priority setting for existing chemicals: Automated data selection routine

One of the four steps within Council Regulation 793/93/EEC on the evaluation and control of existing chemicals is the priority setting step. The priority setting step is concerned with selecting high-priority substances from a large number of substances, initially starting with 2,474 high-production-volume chemicals. In order to be able to...

Changes in the nasal epithelium of rats exposed by inhalation to mixtures of formaldehyde, acetaldehyde, and acrolein

Formaldehyde, acetaldehyde, and acrolein are well-known upper respiratory tract irritants and occur simultaneously as pollutants in many indoor and outdoor environments. The upper respiratory tract, and especially the nose, is the prime target for inhaled aldehydes. To study possible additive or interactive effects on the nasal epithelium we...

Toxicity of formaldehyde and acrolein mixtures: In vitro studies using nasal epithelial cells

In vitro studies with human and rat nasal epithelial cells were carried out to investigate the combined toxicity of formaldehyde and acrolein and the role of aldehyde dehydrogenases in this process. These studies showed that the toxic effect of mixtures of aldehydes was additive. In addition, aldehyde dehydrogenases were inhibited by disulfiram...

Inhibition of glutathione S-transferase activity in human melanoma cells by alfa, beta-unsaturated carbonyl derivatives: Effects of acrolein, cinnamaldehyde, citral, crotonaldehyde, curcumin, ethacrynic acid, and trans-2-hexenal

The glutathione S-transferase (GST) activity towards 1-chloro-2,4-dinitrobenzene in intact human IGR-39 melanoma cells was determined by the quantification by HPLC-analysis of the excreted glutathione (GSH) conjugate (S-(2,4-dinitrophenyl)glutathione; DNPSG). The major GST subunit expressed in these melanoma cells is the π-class GST subunit P1....

Sensory irritation to mixtures of formaldehyde, acrolein, and acetaldehyde in rats

Sensory irritation of formaldehyde (FRM), acrolein (ACR) and acetaldehyde (ACE) as measured by the decrease in breathing frequency (DBF) was studied in male Wistar rats using nose-only exposure. Groups of four rats were exposed to each of the single compounds separately or to mixtures of FRM, ACR and/or ACE. Exposure concentrations of the...

Repeated exposure to alpha-ethylacrolein vapour: Subacute toxicity study in rats

The subacute inhalation toxicity of ??-ethylacrolein was examined in rats by repeated exposure of 4 groups of 10 males and 10 females each to ??-ethylacrolein vapour at concentrations of 0, 2.0, 9.8 or 48.4 ppm, respectively, (6 h/day, 5 days/week) for a period of 13 weeks. The effects at 48.4 ppm were found to include growth retardation, focal...

Repeated exposure to acrolein vapour: Subacute studies in hamsters, rats and rabbits

The subacute inhalation toxicity of acrolein was examined in 4 groups of 20 hamsters, 12 rats and 4 rabbits each, exposed repeatedly to acrolein vapour at concentrations of 0, 0.4, 1.4 and 4.9 ppm (6 hr/day, 5 days/week) for a 13-week period. The most important effects found at the highest level included mortality in rats, ocular and nasal...