Hemimellitene (1,2,3-trimethylbenzene) in the liver, lung, kidney, and blood, and dimethylbenzoic acid isomers in the liver, lung, kidney and urine of rats after single and repeated inhalation exposure to hemimellitene.

OBJECTIVES: The aim of the study has been to explore hemimellitene distribution in blood, liver, lung and kidney as well as toxicokinetics of its elimination from blood of rats after single and repeated inhalation exposure to this compound. Tissue distribution and excretion with urine of 2-dimethylbenzoic acids (2,3-DMBA and 2,6-DMBA) were also evaluated. MATERIAL AND METHODS: Male outbred IMP:WIST rats were used in the experiment. The animals were exposed to hemimellitene vapors at the nominal concentration of 25 ppm, 100 ppm, and 250 ppm in the dynamic inhalation chambers for 6 h for single exposure purpose and for 4 weeks (6 h/day for 5 day/week) for repeated exposure purposes. RESULTS: Significantly lower concentrations of hemimellitene were detected in the blood and tissues of animals after repeated inhalation exposure of animals to hemimellitene vapors, which points to reduced retention of the chemical in the lungs of the experimental rats. The trend of hemimellitene elimination from the blood depended solely on exposure intensity, irrespective of exposure time, both after single and repeated exposure. As regards the 2 determined hemimellitene metabolites, the major trend of the metabolic transformation involved formation of 2,3-DMBA. CONCLUSIONS: The significantly higher urinary 2,3-DMBA concentration after repeated exposure shows that hemimellitene induces enzymatic processes in the rat.

Toxic effect in the lungs of rats after inhalation exposure to benzalkonium chloride.

BACKGROUND: Benzalkonium chloride (BAC) is a quaternary ammonium compound (QAC) toxic to microorganisms. Inhalation is one of the major possible routes of human exposure to BAC. MATERIALS AND METHODS: Experiments were performed on female Wistar rats. The rats were exposed to aerosol of BAC water solution at the target concentration of 0 (control group) and 35 mg/m(3) for 5 days (6 h/day) and, after a 2-week interval, the animals were challenged (day 21) with BAC aerosol at the target concentration of 0 (control group) and 35 mg/m3 for 6 h. RESULTS: Compared to the controls, the animals exposed to BAC aerosol were characterized by lower food intake and their body weight was significantly smaller. As regards BAC-exposed group, a significant increase was noted in relative lung mass, total protein concentration, and MIP-2 in BALF both directly after the termination of the exposure and 18 h afterwards. Significantly higher IL-6 and IgE concentrations in BALF and a decrease in the CC16 concentration in BALF were found in the exposed group immediately after the exposure. The leukocyte count in BALF was significantly higher in the animals exposed to BAC aerosol compared to the controls. In the lungs of rats exposed to BAC the following effects were observed: minimal perivascular, interstitial edema, focal aggregates of alveolar macrophages, interstitial mononuclear cell infiltrations, thickened alveolar septa and marginal lipoproteinosis. CONCLUSION: Inhalation of BAC induced a strong inflammatory response and a damage to the blood-air barrier. Reduced concentrations of CC16, which is an immunosuppressive and anti-inflammatory protein, in combination with increased IgE concentrations in BALF may be indicative of the immuno-inflammatory response in the animals exposed to BAC aerosol by inhalation. Histopathological examinations of tissue samples from the BAC-exposed rats revealed a number of pathological changes found only in the lungs.

4-Week inhalation toxicity of 2-methylnaphthalene in experimental animals.

OBJECTIVES: This paper presents toxic effects of 2-MN in laboratory animals under conditions of 4-week inhalation exposure to 2-methylnaphthalene (2-MN) vapors. MATERIALS AND METHODS: Male Wistar rats were exposed to 2-MN vapors at a nominal concentration of 0, 2, 10 or 50 mg/m(3) in dynamic inhalation chambers for 4 weeks (6 h/day, 5 days/week). After 4 weeks of inhalation exposure the animals were necropsied. Blood samples were collected and selected organs were weighted and prepared for histological examinations. RESULTS: The effects of the increased levels of exposure to 2-MN experienced by the experimental rats were as follows: a) increasing γ-glutamylotransferase activity, b) stimulation of the hematopoietic system, c) lower cholesterol concentrations, d) higher number of goblet cells in lobar bronchi, e) hyperplasia of hepatic bile ducts. CONCLUSION: Four-week exposure of the animals to 2-MN at 2 mg/m(3) proved to be the no-observed-adverse-effect-level (NOAEL), while 10 mg/m(3) appeared to represent the lowest-observed-adverse-effect-level (LOAEL).

Contrasting effects of 4-week inhalation exposure to pseudocumene or hemimellitene on sensitivity to amphetamine and propensity to amphetamine sensitization in the rat.

OBJECTIVES: Some data suggest that increased behavioural sensitivity to psychostimulants may develop after exposure to volatile chemicals in common use. The purpose of the present experiment was to find out whether and in what way inhalation exposure to pseudocumene (PS) or hemimellitene (HM) at low concentrations alters behavioural sensitivity to the psychostimulant amphetamine (AMPH), and propensity to develop behavioural sensitization to AMPH. MATERIAL AND METHODS: Adult male Wistar rats were exposed 6 h/day, 5 days a week for 4 weeks to PS or HEM at 0, 25, 100 or 250 ppm. Behavioural sensitivity to AMPH was assessed by measuring locomotor activity of the animals in an open-field. Behavioural sensitization to AMPH was induced by a repeated AMPH treatment. RESULTS: In rats exposed to HEM, the behavioural sensitivity to AMPH was increased, but remained unchanged in rats exposed to PS. The second testing revealed an augmented behavioural response to AMPH in control rats. In the HM exposed rats this augmenting was significantly more evident and in the PS exposed rats significantly less evident than in controls. For each of the two solvents, the concentration-effect relationship was nonlinear; out of the three concentrations used, 100 ppm was the most effective. CONCLUSIONS: The results confirm that low-level inhalation exposure to trimethylbenzene isomers may induce behavioural sensitisation and/or increase the susceptibility of the animals to develop this state upon repeated psychostimulant treatment. They show, however, that HM and PS differ markedly in their ability to induce such alterations.

The toxicokinetics of 2-methylnaphtalene in rats.

BACKGROUND: The aim of the study was to evaluate the toxicokinetics of 2-methylnaphtalene (2-MN) during and after inhalation exposure. MATERIAL AND METHODS: Male Wistar rats were exposed to 2-MN vapours at nominal concentrations of 200 or 400 mg/m3 in the dynamic inhalation chamber for 6 hours or 5 days (6 h/day). Blood samples were collected during and after exposure. Blood concentrations of 2-MN were estimated by gas chromatography using the headspace technique. RESULTS: During a 6-hour exposure to 200 or 400 mg/m3, blood 2-MN concentration increased rapidly within the first or second hour of exposure, respectively, after reaching a plateau. The elimination of 2-MN from blood followed an open two-compartment model. CONCLUSION: 2-MN was rapidly eliminated from blood of the animals exposed by inhalation to 2-MN. During exposure, lung retention of the chemical was found to decrease. Under conditions of repeated 2-MN exposure, no significant systemic 2-MN accumulation could be observed.

Pulmonary irritation after inhalation exposure to benzalkonium chloride in rats.

BACKGROUND: Benzalkonium chloride (BAC) is a quaternary ammonium compound (QAC) with a C8 to C18 chain length of alkyl groups. Since BAC exerts toxic effects on microorganisms, it has been used as an effective germicide and preservative, mostly in cosmetic industry and medicine. However, the toxic potential of BAC may be hazardous to humans, due to the common use of preparations containing BAC as a preservative. MATERIAL AND METHODS: To assess the possible toxic effects of BAC, two-stage experiments were performed on female Wistar rats. At first, LC50 after a single exposure to BAC aerosol was determined. Then, the animals were exposed to BAC aerosol at 30 mg/m3 for 6 h, and for 3 days (6 h/day). The controls were unexposed rats. Directly after BAC exposure and 18 h afterwards, BALF concentrations were measured of total protein, Clara cell protein, matrix metalloproteinase-9 (MMP-9), hyaluronic acid (HA), immunoglobulin E (IgE) and cytokines (TF-alpha, IL-6 and MIP-20), lactate dehydrogenase (LDH) and GSH-S-transferase (GST). RESULTS: The LC50 value for exposed rats was ca. 53 mg BAC in m3 air for 4 h. All the rats survived single and repeated inhalation exposure to 30 mg/m3 BAC. After single and repeated exposure, lung weight, total protein, HA and LDH activity in BALF of exposed rats were higher than in controls while CC16 levels were decreased. A significantly higher BALF concentration of IL-6 and IgE was noted in animals exposed to single and repeated doses. BALF concentrations of MMP-9, TNF-alpha, and MIP-2 in exposed rats were similar to those in control animals. CONCLUSION: BAC may be classified to class I acute inhalation toxicity. It showed a strong inflammatory and irritant activity on the lungs after 6h inhalation and stimulated dynamic patterns of IL-6 and IgE production and protein infiltration from blood vessels to BALF. Continued exposure resulted in cellular destruction, a statistically significant increase in LDH activity and a continuous decrease in CC16 concentration in BALF.

[Toxic effect of benzalkonium chloride on animals and humans]. / Toksyczne dzialanie chlorku benzalkoniowego na zwierzeta i ludzi.

Benzalkonium chloride (BAC) exerts toxic effects on microorganisms. This property has been utilized in the cosmetic industry and medicine, where it is used as effective germicide and preservative agents. Various BAC-containing preparations used by people may induce a number of adverse effects on the human body. Bearing in mind that BAC is widely used in different branches of the national economy, its toxic effect may cause a health problem of significant importance to humans. The authors describe BAC toxic effects exerted on humans and laboratory animals as well as relevant hazards resulting from the use of BAC-contained preparations.

Toxicokinetics and metabolism of pseudocumene (1,2,4-trimethylbenzene) after inhalation exposure in rats.

The objective of this study was to evaluate the toxicokinetics and metabolism of pseudocumene after inhalation exposure. Male Wistar rats were exposed to pseudocumene vapors at nominal concentrations of 25,100 or 250 ppm in the dynamic inhalation chambers for 6 h. Blood samples were collected during (between 1st and 6th h) and after exposure (betwen 6th min and 6th h). Blood concentrations of pseudocumene were estimated by gas chromatography using the headspace technique. During a six-hour exposure, the concentration of pseudocumene in blood increased rapidly within the first 2 h reaching then a plateau. The elimination of pseudocumene from blood followed an open two-compartment model. Urine samples were collected from the exposed animals, and metabolites were analyzed by gas chromatography with a flame ionization detector. Three metabolites were measured in the rat urine after hydrolysis: 3,4-dimethylbenzoic acid (3,4-DMBA), 2,4-dimethylbenzoic acid (2,4-DMBA) and 2,5-dimethylbenzoic acid (2,5-DMBA). A significant linear correlation was found between the level of exposure and the concentration of dimethylbenzoic acids. The enzyme kinetics of pseudocumene biotransformation was calculated by Lineweaver-Burk equation. Metabolic constants, Km (mg/l) and Vmax (mg/h/kg), the parameters for pseudocumene biotransformation by rats were estimated (3,4-DMBA - Km = 28, Vmax = 96; 2,4-DMBA - Km = 7, Vmax = 25; 2,5-DMBA - Km = 7, Vmax = 23).