Ih Chu

Reproductive and Thyroid Hormone Levels in Rats Following 90-Day Dietary Exposure To Pcb 28 (2,4,4'-Trichlorobiphenyl) or Pcb 77 (3,3',4,4'-Tetrachlorobiphenyl):

Subchronic exposure to the PCB congener 77 (PCB 77) and 28 (PCB 28) was previously shown to induce histological changes in the thyroid and in the brain biogenic amines levels, suggesting possible effects on thyroid and reproductive hormone levels. Thus, the effects of a 90-day dietary exposure to PCB 28 or 77 on luteinizing hormone, follicle-stimulating hormone, and testosterone concentrations were studied in male rats, as well as the levels of thyroid-stimulating hormone, thyroxine (T4) and uridine diphosphate-glucuronyl transferase (UDP-GT) activity in both genders. Weanling Sprague Dawley rats were randomly distributed into groups of 10 rats and were fed, for the next 13 weeks, purina lab chow containing 50, 500, 5000, or 50 000 ppb of PCB 28 or 10, 100, 1000, or 10 000 ppb of PCB 77. The serum concentrations of T4 were decreased in rats of both sexes receiving 1000 ppb or more of PCB 77, and was associated with an increased activity of UDP-GT which reached significance only in the females. There was a tendency for the highest dose of PCB 28 also to decrease serum T4 concentrations in the female rats. None of the PCB treatments significantly altered gonadotropin, TSH, or testosterone concentrations. These results suggest that thyroid functions may be more susceptible or adapt less readily than the pituitary gland and the testes to endocrine disruption caused by PCB congeners.

Short-Term Inhalation Toxicity of Methanol, Gasoline, and Methanol/Gasoline in the Rat

Four- to five-week-old male and female Sprague Dawley rats were exposed to vapors of methanol (2500 ppm), gasoline (3200 ppm), and methanol/gasoline (2500/3200 ppm, 570/3200 ppm) six hours per day, five days per week for four weeks. Control animals were exposed to filtered room air only. Depression in body weight gain and reduced food consumption were observed in male rats, and increased relative liver weight was detected in rats of both sexes exposed to gasoline or methanol/gasoline mixtures. Rats of both sexes exposed to methanol/gasoline mixtures had increased relative kidney weight and females exposed to gasoline and methanol/gasoline mixtures had increased kidney weight. Decreased serum glucose and cholesterol were detected in male rats exposed to gasoline and methanol/gasoline mixtures. Decreased hemoglobin was observed in females inhaling vapors of gasoline and methanol/gasoline at 570/3200 ppm. Urine from rats inhaling gasoline or methanol/gasoline mixtures had up to a fourfold increase in hippuric acid, a biomarker of exposure to the toluene constituent of gasoline, and up to a sixfold elevation in ascorbic acid, a noninvasive biomarker of hepatic response. Hepatic mixed-function oxidase (aniline hydroxylase, aminopyrine N-demethylase and ethoxyresorufin O- deethylase) activities and UDP-glucuronosyltransferase activity were elevated in rats exposed to gasoline and methanol/gasoline mixtures. Histopathologicalchanges were confined to very mild changes in the nasal passages and in the uterus, where decreased incidence or absence of mucosal and myometrial eosinophilia was observed in females inhaling gasoline and methanol/gasoline at 570/3200 ppm. It was concluded that gasoline was largely responsible for the adverse effects, the most significant of which included depression in weight gain in the males, increased liver weight and hepatic microsomal enzyme activities in both sexes, and suppression of uterine eosinophilia. No apparent interactive effects between methanol and gasoline were observed.

Results of a short-term toxicity study for three organic chemicals found in Niagara river drinking water

During the past decade concern has been raised over the quality of drinking water in the communities that draw their supply directly from the Niagara River, which is known to be contaminated with a number of chemical pollutants. At the present, attention is focused on trace organic chemicals in the Niagara River and in Lake Ontario. These substances originate directly from municipal and industrial discharges and indirectly from major waste disposal sites along the river. Dibromomethane, hexanal and tetrahydrofuran among other chemicals were detected in treated drinking water at levels ranging from 0.2-0.8 ..mu..g/L in the Niagara River area. There are no toxicity data available on these chemicals when they are administered to laboratory animals in drinking water. Since the mode of administration may affect the pharmacokinetic behavior and hence the toxic effects of these compounds, it was considered that further animal studies were needed for the regulatory agencies to assess the potential adverse effects in humans associated with the ingestion of the organic chemicals via drinking water. To this end short-term toxicity studies (4 weeks) on dibromomethane, hexanal, and tetrahydrofuran in the rat were carried out.

Subchronic study of a mixture of inorganic substances present in the Great Lakes ecosystem in male and female rats

ConclusionThe oral administration of inorganic substances at levels up to 25 times greater than the objectives established in the Great Lakes Water Quality Agreement for 13 weeks did not cause any observed toxic effects in the rat.

Short-term toxicity of nine industrial chemicals

There are a number of industrial chemicals currently used in Canada in sufficiently large quantities that warrant a careful environmental and human health hazard assessment by the regulatory agencies. A review of the existing toxicity data for these chemicals indicated that most of the studies were inadequate due to study design, small group size, inadequate procedures or insufficient parameters being monitored. In order to determine if further studies were warranted it was decided to screen 9 of these chemicals in a short-term study using male and female rats. The chemicals were chosen based on considerations such as quantity, availability of toxicological data, chemical and structural properties and commercial availability. The chemicals selected were: tri(butoxyethyl) phosphate, dimethylol urea, 2-butyne-1,4-diol, triallyl-s-triazine-trione, cyclohexanone oxime, p-toluene sulphonhydrazide, 2-nitroaniline, propargyl alcohol and 5-methyl-1H-benzotriazole. The assay consisted of a 14-day oral dosing regime followed by a comprehensive evaluation of biochemical, hematological and histophathological changes.

Metabolism of nitrilotriacetic acid (NTA) in the mouse

Nitrilotriacetic acid (NTA) is a good sequestering agent and is being used as a partial replacement for the phosphates in household detergent formulations. Despite the fact that the metabolism of this compound has been studied in the rat, rabbit, dog, monkey (MICHAEL and WAKIM, 1971) and in humans (BUNDY and ARNOLD, 1973) pharmacokinetic data for NTA in the mouse have been lacking. A previous report dealt with distribution of t~C-NTA in mice by whole-body autoradiography (TJALVE, 1972) but no absorption and metabolic excretion data were available. The present studies were carried out as part of a general program on NTA and were designed to determine the absorption, distribution and metabolic excretion of NTA in the mouse.

Absorption, distribution and metabolism of epoxystearic acid in the rat

ConclusionEpoxystearic acid was rapidly absorbed after oral administration and well distributed in all tissues, mainly in the fat and liver of rats. Since this compound was metabolized to CO2 and was removed in the expired air, little or no bioaccumulation could be expected.

Comparative Toxicity and Metabolism of Tetrachlorobenzene Isomers

LD50 values for 1,2,3,4-, 1,2,4,5- and 1,2,3,5-tetrachloro- benzene (TCB) were found to be 1470, 3105 and 2297 mg·kg-1, respectively, in male rats. In females the LD50 values were found to be 1167 and 1727 mg·kg-1 for 1,2,3,4- and 1,2,3,5-TCB, respectively. Clinical signs of toxicity included depression, flaccid muscle tone, prostration, piloerection, loose stool, hypothermia, dacryorrhea, coma and death. In a subacute study, rats were fed diets containing 0, 0.5, 5.0, 50 or 500 ppm 1,2,3,4-, 1,2,4,5- or 1,2,3,5-TCB for 28 days. At 500 ppm 1,2,4,5-, but not 1,2,3,4- or 1,2,3,5-TCB, caused a significant increase in the liver weight, and serum cholesterol of male and female rats. Hepatic microsomal aniline hydroxylase was induced by 500 ppm 1,2,4,5-TCB. Hepatic microsomal aminopyrine demethylase activity was increased by the administration of this compound at 50 ppm and higher in males and at 500 ppm in the females. Rats fed 1,2,3,4- and 1,2,3,5-TCB at 500 ppm also showed a significant increase in aminopyrine demethylase activity. Moderate to severe histological changes were found in the liver, thyroid, kidney and lungs of rats fed 500 ppm 1,2,4,5-TCB. Histological changes in the tissues produced by the administration of the 1,2,3,4- and 1,2,3,5- isomer were mild even at the highest dose levels. Similar results were observed in rats fed TCB isomers for 90 days. However, histopathological changes in the kidney of rats fed 1,2,4,5-TCB were more severe than those of the subacute study. Tissue residue data showed that 1,2,4,5-TCB accumulated in a dose-dependent manner and at much higher concentrations than the other two isomers. In a separate study adult male rats were given orally single doses of 14C-l, 2,3,4-, or 1,2,4,5-TCB at 10 mg·kg-1 body weight, and were housed in individual metabolism cages to collect urine and feces for radio- assay. The fat, skin and liver of rats dosed with 1,2,4,5-TCB contained the highest levels of radioactivity, whereas little 14C was detected in 1,2,3,4- and 1,2,3,5-TCB treated animals. For 1,2,3,4- and 1,2,3,5-TCB, approximately 46% to 51% of the administered compound were excreted in urine and feces within 48 hours after administration. During the same period only 8% of the administered 1,2,4,5- Tetrachlorobenzene was excreted. Analysis of urine indicated that the tetrachlorobenzenes were biotransformed to a number of polar metabolites. The metabolites for each of the three TCB’s in decreasing order of quantities were as follows; for 1,2,3,4-TCB: 2,3,4,5- and tetrachlorophenol and a trace of tetrachlorothiophenol and 2, 3,4-trichlorophenol; for 1,2,3,5-TCB: 2, 3, 4, 6-tetrachlorophenol, isomeric mercaptotrichlorophenols and a trichlorophenol; for 1,2,4,5-TCB: 2,3,5,6-tetrachlorophenol, tetrachloroquinol and a trichlorophenol. Data indicate that 1,2,4,5-TCB was much more toxic than the other two TCB isomers, and that the differences in toxicity were associated with a higher degree of bioaccumulation and slower metabolic degradation of this compound.

The pharmacokinetics of benzo(a)pyrene in the rat

Groups of 4 male Wistar rats were dosed intravenously with 14C-labeled benzo[a]pyrene dissolved in an Emulphor/water vehicle at 3 different dose levels and killed at 1 of 15 specific time intervals from 5 min to 32 h after dosing. 14C-Radiolabel concentration-time data were obtained for blood, brain, adipose, heart, kidney, liver, lung, spleen, and testes. Benzo[a]pyrene concentration-time data were obtained for blood, adipose, kidney, liver, and lung. Appropriate mathematical models were fitted to these data and to the data for metabolites derived as the residuals from 14C-radiolabel minus benzo[a]pyrene difference, where applicable. Nonlinear kinetics were found for 14C-radiolabel in liver, while the data from lung for both 14C-radiolabel and for benzo[a]pyrene per se supported the binding of benzo[a]pyrene in that tissue.

Effect of lead on tissue disposition of nitrilotriacetic acid (NTA) in rats

Nitrilotriacetic acid (NTA) is a good sequestering agent and is being used as a partial replacement for phosphates in certain household detergent formulations. NIXON et al. (1972) and MICHAEL and WAKIM (1971) reported the toxicity of NTA in rats. NOLEN et al. (1972) showed that orally administered NTA would decrease tissue concentrations of cadmium but had no detectable effect on tissue concentrations of methylmercury in rats. Little information is available on the effect of lead on the tissue disposition of NTA in rats. The present studies were part of our general investigations into the toxicities of NTA in mammals, and were designed to study the tissue disposition of NTA in rats previously treated with lead (as lead acetate).