Subchronic inhalation toxicity of 1,2,3-trimethylbenzene (hemimellitene) in rats.

Toxic effects of exposure to 1,2,3-trimethylbenzene (hemimellitene) in the condition of subchronic inhalation experiment were examined. Rats were exposed to vapours of hemimellitene at concentrations of 123 mg/m3, 492 mg/m3 and 1230 mg/m3, 6 h/day, 5 days/week for 3 months. After termination of a 3-month inhalation, animals were necropsied. Blood samples were obtained and selected organs were weighed and prepared for histological examinations. Subchronic inhalation exposure to hemimellitene resulted in an overall, low systemic toxicity. There were no changes in body weight gain and food consumption. At a concentration of 1230 mg/m3, the increase in relative liver weight was observed in male rats. It was accompanied by slight increase in sorbitol dehydrogenase activity. The increase in alkaline phosphatase activity was found in females only. Some disturbances in haematological parameters, characterised by the decrease in red blood cells and slight increase in white blood cells, segmented neutrophils and lymphocytes were observed in rats at high exposure concentration of 1230 mg/m3. The pulmonary lesions as well as the increased number of goblet cells and interstitial lung parenchyma infiltration were noted in male and female rats from the highest exposure groups.

Sub-chronic inhalation toxicity of 1,2,4-trimethylbenzene (pseudocumene) in rats.

Toxic effects of exposure of 1,2,4-trimethylbenzene (pseudocumene) in the condition of sub-chronic inhalation experiment were examined. Rats were exposed to vapours of pseudocumene at concentrations of 123 mg/m3, 492 mg/m3 and 1230 mg/m3, 6 h/day, 5 days/week for 3 months. After 3 months of inhalation exposure animals were necropsied. Blood samples were obtained and selected organs were weighted and prepared for histological examinations. Sub-chronic inhalation exposure to pseudocumene resulted in an overall low degree of systemic toxicity. There were no changes in body weight gain, food consumption and absolute and relative organ weights. Slightly higher activity of sorbitol dehydrogenase was observed in male rats exposed to all concentrations applied. Some disturbances in hematological parameters characterised by decrease in red and increase in white blood cells were observed in male rats exposed to high concentration of 1230 mg/m3. The pulmonary lesions observed in male and female rats were statistically significant at mid and high concentrations of pseudocumene.

A subchronic toxicity study of Rokanol B-2 in rats.

The toxicity of Rokanol B-2 was assessed following its administration to rats via oral gavage. A preliminary study of acute toxicity was performed to determine suitable dosing regimen/dose levels for future repeated-dose toxicity studies. For this purpose rats (15 males and 7 females) received single doses of 2,000, 1,500, 1,000 or 500 mg/kg and were killed after 2 or 14 days. No deaths occurred during the observation time. Dose-related irritation to the stomach mucosa was found. For the subchronic toxicity assessment, Rokanol B-2 was administered at daily doses of 8, 40 or 200 mg/kg to 59 male and 56 female Wistar rats by oral gavage, 5 days per week for 90 days. An interim experiment was performed after 28 days of dosing. Five animals/sex/group were terminated and necropsied. Blood samples for clinical chemistry and haematology were obtained and lungs, heart, adrenals, kidneys, liver, spleen, stomach, intestine, testes (males), uterus and ovaries (females) were weighed and prepared for histopathological examination. After 90 days of dosing all remaining animals were killed and necropsied. Blood samples were taken for evaluation of haematology and clinical chemistry, and selected organs (same as above) prepared for subsequent histological examination. In the high-dose group (200 mg/kg/day) a statistically significant reduction in body weight gain and food consumption, an increased weight of the liver in the males and disturbances in haematological parameters in the females were observed. Ulcerations of the mucous membrane of the stomach and hyperkeratosis, and in a few cases, pseudopapillomatous epithelial proliferation of foregaster and exudate in the submucosa of the stomach were noted. In the mid-dose group (40 mg/kg/day) some disturbances in hematological parameters in females and histopathological changes in rats of both sexes similar, but to a lesser degree, to changes observed in high-dose animals were indicated. In the low-dose group (8 mg/kg/day) no significant treatment-related effects were observed. The results of this study indicate that Rokanol B-2 possessed an overall low degree of systemic toxicity when administered orally to rats for 90 days. The NOAEL, observed in this study, was estimated as 8 mg/kg/day.

Acute toxicity of 2-butyne-1,4-diol in laboratory animals.

Acute toxicity of 2-butyne-1,4-diol (BYD) was evaluated in laboratory animals. The evaluation involved acute oral and dermal toxicity in rats, dermal and ocular irritation in rabbits and skin sensitization in guinea pigs. The oral LD50 values for BYD were 132 mg kg-1 in male rats and 176 mg kg-1 in female rats. Post-mortem histology showed severe damage in lungs, liver and kidneys. In surviving rats, moderate to severe degenerative changes were observed in the liver but only mild lesions in the kidneys. In acute dermal toxicity studies the test chemical was applied either as a solid substance or as 40% aqueous solution at a dose of 5 g kg-1 for 24 h. Within 48 h of application of the diluted test material, half of the rats died. Liver and kidneys were the primary targets and different stages of degeneration, including necrosis, were observed. No deaths occurred after application of the solid substance. In rabbits, BYD was slightly irritant to skin and eyes. No allergic contact dermatitis was observed in guinea pigs.

Subacute oral toxicity of 2-butyne-1,4-diol in rats.

2-Butyne-1,4-diol was given to male and female Wistar Imp:DAK rats by oral gavage for 28 consecutive days in daily doses of 1, 10 or 50 mg kg-1 day-1. After 28 days all animals were necropsied. Blood samples were obtained and selected organs were weighed and prepared for histological examination. Treatment-related effects in the high-dose group consisted of: fatal cases in both sexes; depressed body weight gain in males; increase of absolute and/or relative weights of liver and kidneys in both sexes; decreased red blood cell count, haematocrit value and haemoglobin concentration in female rats and elevated reticulocyte count and leukocyte count in both sexes; increased total serum protein content in females, elevated glucose concentration in males and higher activity of sorbitol dehydrogenase in both sexes; and histopathological evidence of hepatotoxicity and nephrotoxicity in decedents, and hepatic and splenic changes in survivors. Minor hepatic, splenic and erythrocytic changes were also found in some females given the middle dose. The dose of 1 mg kg-1 day-1 was considered to be the no-observed-effect level (NOEL), and 10 mg kg-1 day-1 the lowest-observed-effect level (LOEL).

Acute toxicity of 1,4-butanediol in laboratory animals.

Acute toxicity of 1,4-butanediol (BAD) was evaluated in laboratory animals. The evaluation involved acute oral and dermal toxicity in rats, dermal and ocular irritation in rabbits, and skin sensitization in guinea pigs. The oral LD50 values for BAD were 1.83 g/kg and 2.00 g/kg, respectively for male and female rats. The histopathological changes were observed in the liver and kidneys. No mortality was observed in female rats after dermal application of BAD at a dose of 5 g/kg. The histopathological lesions were comparable to those observed in rats after oral gavage. BAD was slightly irritant to the skin and eye of rabbits. No allergic contact dermatitis was observed in guinea pigs.

Subacute oral toxicity of 1,4-butanediol in rats.

1,4-Butanediol (BAD) was administered to male and female Wistar Imp:DAK rats by oral gavage for 28 consecutive days. Treated rats received BAD at daily doses of 5, 50 or 500 mg/kg/day. After 28 days all animals were necropsied. Blood samples were obtained and selected organs were weighed and prepared for histological examination. Subacute oral administration of BAD resulted in an overall low degree of systemic toxicity. There were no changes in body weight, food consumption, and absolute and relative organ weights. Slightly higher activities of sorbitol dehydrogenase and alanine aminotransferase were observed in male rats given BAD at the highest dose of 500 mg/kg/day. Some disturbances in hematological parameters, characterized by macrocytosis and thrombocytopenia were observed in treated rats. Mild to moderate inflammation of the liver, characterized by proliferation of bile ducts and periportal infiltrations with fibroblasts and mononuclear cells, were found in treated animals. A statistically significant difference for histopathological changes was found in animals treated with BAD at the dose of 500 mg/kg/day only in the case where both sexes were jointly taken for comparison.

Computer image analysis of toxic fatty degeneration in rat liver.

Fatty degeneration of the liver is one of the most frequently observed pathological changes in the experimental estimation of the toxicity of chemical compounds. The intensity of this kind of damage is most often detected by means of a generally accepted scale of points, whereas the classification is performed according to the subjective "feeling" of the pathologist. In modern pathological diagnostics, computer analysis of images is used to perform an objective estimation of the degree of damage to various organs. In order to check the usefulness of this kind of method, comparative biochemical and morphometrical studies were undertaken in trichloroethylene (TRI)-induced fatty degeneration of the liver. TRI was administered to rats intragastrically, in single doses: 1/2; 1/3; 1/4; 1/6 and 1/18 DL50. 24 hours after the administration, the animals were sacrificed. The content of triglycerides in the liver was determined according to Folch et al. (1956). Simple lipids in the histochemical samples were detected by means of staining with a lipotropic, Fat Red 7B. The area of fatty degeneration was estimated in the microscopic samples by the use of an automatic image analyser IBAS 2000 (Kontron). The morphometrical data concerning the area of fatty degeneration in the liver amplified a high degree of correlation with the content of triglycerides (r = 0.89) and the dose of TRI (r = 0.96). The degree of correlation between the biochemical data and the dose of TRI was 0.88. The morphometrical studies performed have proved to be of great use in estimating the degree of fatty degeneration in the liver. This method enables precise, quantitative measuring of this sort of liver damage in the material prepared for routine histopathological analysis. It requires, however, the application of a specialized device for quantitative image analysis.

Effects of oral, subchronic cadmium administration on fertility, prenatal and postnatal progeny development in rats.

Cadmium chloride was administered by gavage to female rats 5 days a week for 5 weeks, then during mating and gestation periods at doses of 0.04, 0.4, and 4 mg Cd/kg/day. Treatment with cadmium neither affected the survival and fertility of females, nor produced overt fetotoxic effects. Fetal cadmium concentration was not related to the level of exposure. Litter size, body weight gain and viability of offspring during 2 months after parturition were similar in all groups. The exploratory locomotor activity of 2-month-old males and females born to rats given 0.4 and 4 mg Cd/kg/day was significantly reduced. The progeny of cadmium-treated females showed decreased performance in the rotarod test. In general, the degree of behavioral impairment was dose-related.

Teratogenicity, fetal toxicity and tissue concentration of cadmium administered to female rats during organogenesis.

Cadmium chloride was administered by gavage to pregnant rats from day 7 to day 16 of gestation. Cadmium, when administered at a dose of 40 mg Cd per kg per day, was associated with significant maternal toxicity, placental injury and an increased fetal burden of cadmium. At lower dose levels (2-20 mg Cd per kg per day), fetal development was retarded. Teratogenic effects were not observed and the fetal cadmium concentrations did not differ significantly from the controls, despite the marked cadmium accumulation in the placenta and maternal tissues. The body-weight gain during gestation of all cadmium-treated females was reduced and an absolute weight of adrenals in females given cadmium at doses 4 mg kg-1 and higher was significantly increased. The obtained results indicate that cadmium-induced fetal toxicity is associated with concomitant maternal toxicity and alteration in placental function.

[Evaluation of acute and subacute toxic effects of polactine yellow G]. / Ocena ostrego i podostrego toksycznego dzialania zólcieni polaktynowej G.

In acute experiment the following results were obtained: the DL50 value after intragastric administration -- 8.2 g/kg of body weight, after intraperitoneal administration -- 1.33 g/kg of body weight. In the studies on acute effect irritating skin and eye of a rabbit -- only a slight inflammatory reaction in conjunctivae was found. Studies on sensitizing effect carried out on guinea pigs did not reveal any symptoms which would give evidence of an alergic effect of the dye. Lima's test did not reveal any cumulative effects of polactine G Yellow, 8-weeks experiment on 30 male rats, administered with 0.5 g/kg and 1.6 g/kg, gave the following results: in the group of rats exposed to 1.6 g/kg an increased excretion of phenol red with urine, lowered activity of aminotranspherases (AspAT and A1AT), increased activity of lactic dehydrogenase and alkaline phosphatase in the blood serum and increased relative liver weight and relative and absolute weight of the kidney. In the group of rats exposed to 0.5 g/kg of polactine yellow G, increased alkaline phosphatase in blood serum and increased relative and absolute liver weight was found. In histopathological studies in acute and subacute experiment, a damage to gastric wall was found. In addition, an increased damage to parenchymatous organs, of reversible degeneration nature, was found.

[Acute toxicity of l-naphthyl chlorocarbonate and o-isopropoxynitrobenzene]. / Ostra toksychnosc chloromrówczanu 4-naftylu i o-izopropoksynitrobenzenu.

The investigated compounds given orally to male rats induced pathological changes mainly in the liver. 1-naphthyl chlorocarbonate caused also necrosis of the stomach mucosa. DL50 of o-isopropoxynitrobenzene and 1-naphthyl chlorocarbonate established for male rats after per os administration amounted to 2,75 g/kg and 2,55 g/kg, respectively. Both substances have local irritant effect on the skin and the eye of rabbit--a mild reaction in case of o-isopropoxynitrobenzene and strong one in case of 1-naphthyl chlorocarbonate administration. 1-naphthyl chlorocarbonate has sensitizing properties, while the other compound has not.