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

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Świercz R., Wąsowicz W., Stetkiewicz J., Gromadzińska J., Majcherek W.
International Journal of Occupational Medicine and Environmental Health
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2011
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vol. 24
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issue 4
399-408
EN
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/m³ 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/m³ proved to be the no-observed-adverse-effect-level (NOAEL), while 10 mg/m³ appeared to represent the lowest-observed-adverseeffect- level (LOAEL).
2
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Tissue reaction to the nickel implants in the guinea pigs

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Kręcisz B., Kieć-Świerczyńska M., Piasecka-Zelga J., Chomiczewska-Skóra D., Stetkiewicz J.
International Journal of Occupational Medicine and Environmental Health
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2012
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vol. 25
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issue 3
251-257
EN
Objectives: The aim of the study was the assessment of local tolerance to nickel implants during 9 months observation in guinea pigs sensitized to nickel before implantation and non-sensitized ones. Materials and Methods: Three groups of guinea pigs were included in the study: 10 sensitized to nickel by the guinea pig maximization test; 10 previously nonsensitized and 10 in control group. In 20 animals (except control group) the nickel implants were inserted in the muscle of the back. After 9 months of observation, the animals were patch-tested with 5% nickel sulfate. Also percentage of eosinophils in peripheral blood was examined. Next, the tissue surrounding the implant and skin from the area of patch tests were collected for the histological examination. Results: In 70% of previously sensitized animals, the patch test confirmed the sensitivity to nickel. In 60% of previously non-sensitized animals, a positive reaction to nickel occurred. The results of patch tests in control group were negative. Percentage of eosinophils in peripheral blood was fourfold higher in animals sensitized to nickel than in control group. In histological examination, in the tissue surrounding the implant a dissimilarity concerning the intensity of cellular infiltration was observed between animals previously allergic and non-allergic to nickel. In the 2 of 10 previously sensitized guinea pigs quite severe inflammatory reactions in the inside of connective tissue capsule were noted which may indicate a local allergic reaction. The histological images of skin collected from the positive patch test site corresponded with the typical allergic contact dermatitis. Conclusions: Nickel implants may cause primary sensitization to nickel. The nature of the histological changes in the tissues around the implants in guinea pigs sensitized to nickel may correspond to an allergic reaction. The examination of percentage of eosinophils in blood of guinea pigs may be useful in assessing the allergenic activity of metal alloys containing nickel.
3
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Fertility and developmental toxicity studies of diethylene glycol monobutyl ether (DGBE) in rats

86%
Sitarek K., Gromadzińska J., Lutz P., Stetkiewicz J., Świercz R., Wąsowicz W.
International Journal of Occupational Medicine and Environmental Health
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2012
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vol. 25
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issue 4
404-417
EN
Objectives The solvent, dimethylene glycol monobutyl ether (DGBE), is a component of latex paints, inks; it is used as a degreasing agent, industrial detergent. The aim of the study was evaluating the effects of DGBE administered by gavage on the estrous cycle and given with drinking water on fertility in rats and early development of their progeny. Materials and Methods Female rats were exposed to DGBE by gavage during 8 weeks at 250, 500 or 1000 mg/kg/day. Vaginal smears were collected during the exposure and 4 weeks after its cessation. Fertility studies were performed in male and female animals exposed to in drinking water. Males were exposed for 10 weeks and then mated with females exposed before mating, during pregnancy and lactation. Young animals were observed during 3 weeks after birth. Results DGBE does not cause disturbances of the menstrual cycle in females. Parameters used to assess the general toxicity indicate that males receiving DGBE in drinking water are more sensitive to this compound than females: significantly greater, dose-dependent relative spleen weight, significant decrease in hematological parameters from 8% to 15% depending on the dose, were observed. Clinical chemistry parameters (HDL-cholesterol, BUN) and some markers of oxidative stress differ between the exposed groups and the control one, but without adverse health effect. The microscopic examination of internal organs did not reveal morphological changes in male and female rats. Conclusion The results of our study on the impact of exposure to DGBE on fertility in rats indicate that the substance administered for 9–10 weeks to females and males at a limit dose of 1000 mg/kg did not impair fertility or viability of their offspring during the first three weeks of life.
4
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Developmental toxicity of N-methylaniline following prenatal oral administration in rats

86%
Sitarek K., Gromadzińska J., Stetkiewicz J., Lutz P., Król M., Domeradzka-Gajda K., Wąsowicz W.
International Journal of Occupational Medicine and Environmental Health
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2016
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vol. 29
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issue 3
479-492
EN
Objectives The objective of the study was to assess prenatal toxicity of N-methylaniline (NMA) administered by gavage to pregnant female rats. Material and Methods Pregnant female rats were administered N-methylaniline in corn oil by gavage at daily doses of 0.8 mg/kg of body weight (b.w.), 4 mg/kg b.w., 20 mg/kg b.w. and 100 mg/kg b.w. from implantation (the 5th day post mating) to the day prior to the scheduled caesarean section (the 20th day of pregnancy). General behavior, body weight, food and water consumption, hematological, biochemical analyses and pathomorphological changes of the dams were recorded. Results All the females survived until the end of the study. The test substance was toxic to pregnant females, even at the lowest of the used doses, i.e., 0.8 mg/kg b.w./day. Lower weight gain during pregnancy and significantly higher NMA-dose-dependent absolute weight of the organs were noted in the exposed females. The females from the groups exposed at doses of 20 mg/kg b.w./day and 100 mg/kg b.w./day developed anemia and showed higher concentrations of free thyroxine (FT3) and free triiodothyronine (FT4) thyroid hormones. Total protein concentration exhibited an increase in all the exposed groups of females. In the prenatal toxicity study, administration of N-methylaniline throughout the embryonic and fetal periods produced embryotoxic effects at doses ranging 4–100 mg/kg b.w./day. Conclusions Considering the data obtained in this study, it is reasonable to assume that N-methylaniline administered orally to pregnant rats is toxic for mothers even at a low dose of 0.8 mg/kg b.w./day. However, this dose was not associated with any significant effects to their offspring. This prenatal exposure level may be considered as no-observed-adverse-effect level (NOAEL) for the progeny and a dose of 4 mg/kg b.w./day as the lowest-observed-adverse-effect level (LOAEL) for the progeny.
5
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Toxic effect in the lungs of rats after inhalation exposure to benzalkonium chloride

86%
Świercz R., Hałatek T., Stetkiewicz J., Wąsowicz W., Kur B., Grzelińska Z., Majcherek W.
International Journal of Occupational Medicine and Environmental Health
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2013
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vol. 26
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issue 4
647-656
EN
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/m³ 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.
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