Developmental toxicity of N-methylaniline following prenatal oral administration in rats

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

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/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

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/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)

Fertility and developmental toxicity studies of diethylene glycol monobutyl ether (DGBE) in rats

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

Tissue reaction to the nickel implants in the guinea pigs

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

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/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

Developmental toxicity of N-methylaniline following prenatal oral administration in rats

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

Evidence for oxidative stress at elevated plasma thiol levels in chronic exposure to carbon disulfide (CS2) and coronary heart disease

OBJECTIVES: Oxidative stress in plasma may be promoted by plasma thiols such as homocysteine. However, other thiols such as glutathione may also exert antioxidant effects in vitro and in vivo. To further investigate whether plasma thiols act as prooxidants or antioxidants, we compared plasma oxidative status in patients with coronary heart disease (CHD) and in subjects occupationally exposed to carbon disulfide (CS(2)). METHODS: Fifty-five subjects chronically exposed to CS(2), 53 CHD patients, and 52 healthy controls were examined. To assess plasma oxidative status, concentrations of thiobarbituric reactive substances (TBARS) and total antioxidative capacity (TAC), as well as ferritin and ceruloplasmin were determined. Antioxidative reserve was assessed by the determination of vitamine E, uric acid, superoxide dismutase, catalase, and glutathion peroxidase. In addition, protein and non-protein plasma thiol levels were measured. RESULTS: Patients in both groups had increased levels of plasma thiols as compared to controls: CS(2)-exposed subjects presented with increased levels of thiols associated with plasma proteins, whereas CHD patients presented with elevated total homocysteine and cysteine levels. TBARS were significantly increased and TAC was significantly decreased both in CS(2)-exposed subjects and in CHD patients. In addition decreased activity of glutathione peroxidase, an antioxidative enzyme inhibited by thiol-containing compounds, was noted in both groups. CONCLUSION: These results demonstrate that regardless of their metabolic origin increased thiols are associated with increased oxidative stress in plasma

Working Report on the Status Quo of Nanomaterials Impact on Health and Environment

Nanotechnology is regarded as one of the key technologies of the future and associated with high expectations by politics, science and economy. Artificially produced nanosized particles and nanoscale system components have new properties which are of importance for the development of new products and applications. Such new properties of materials and substances result from the special properties of surfaces and interfaces and in part, from the geometric shape of the material. In theory nanoparticles (NPs) can be produced from nearly any chemical; however, most NPs that are currently in use today have been made from transition metals, silicon, carbon (single-walled carbon nanotubes; fullerenes), and metal oxides (zinc dioxide and titanium dioxide). Potentially harmful effects of nanotechnology might arise as a result of the nature of the NPs themselves, the characteristics of the products made from them, or aspects of the manufacturing process involved (Borm and Kreyling, 2004). The large surface area, crystalline structure, and reactivity of some NPs may facilitate transport in the environment or lead to harm because of their interactions with cellular material. In the case of nanomaterials, size matters, and could facilitate and exacerbate any harmful effects caused by the composition of the material. The highest risks for humans and the environment are associated with nanomaterials contained in products in the form of free particles. As long as NPs remain firmly embedded in materials, hardly any risk should be expected (Brouwer, 2004). However, it has to be clarified in these cases whether and in which form nanomaterials can be released into the environment during the production process, the use of a product, due to ageing and degradation as well as during disposal and recycling processes. Of course, also in the case of nanomaterials, environmental risk assessment should take into account their entire life cycle