V. E. Valli

Toxicological response of rats fed lake Ontario or Pacific Coho salmon for 28 days

Abstract The present study was undertaken to determine if the feeding of Lake Ontario salmon containing a mixture of chemical contaminants, could produce a toxicological response in rats. Male and female rats were fed freeze‐dried Lake Ontario or Pacific Coho salmon for 28 days at levels of 1.45%, 2.90% and 5.80% of their normal diet. Body weight changes, organ weights, food intake, routine hematology, biochemical parameters, residue levels and gross and microscopic pathological changes were determined. Body weight gain was decreased in all groups of male rats fed Lake Ontario or Pacific salmon but this was attributed to the unpalatibility of the diet since the food intake in these groups was decreased during the first week of the study. No effects were observed on body weight gain or food intake in female rats. Hematological parameters including hemoglobin, hematocrit, white blood count and red blood count were not affected by treatment. Serum potassium levels were significantly decreased in all three gr...

A teratological assessment of four trihalomethanes in the rat

Four trihalomethanes were administered by gavage to Sprague-Dawley rats from day 6 to day 15 of gestation. Chloroform (Ch) was administered at levels of 100, 200 and 400 mg/kg and bromoform (Br), bromodichloromethane (BDCM) and chlorodibromomethane (CDBM) were administered at levels of 50, 100 or 200 mg/kg/day. A separate control was used for each compound. Maternal weight gain was depressed in all groups receiving Ch and at the highest dose levels of BDCM and CDBM. Ch administration caused decreased maternal hemoglobin and hematocrit values at all dose levels and also produced increased serum inorganic phosphorus and cholesterol at the highest dose. Liver enlargement was observed at all dose levels of Ch but in no other treatment groups. Evidence of a fetotoxic response was observed with Ch, CDBM and Br but not BDCM. No dose-related histopathological changes were observed in either mothers or fetuses as a result of treatment. None of the chemicals tested produced any teratogenic effects.

Ninety-day toxicity of photomirex in the male rat

Photomirex (8-monohydromirex) is a demonstrated environmental contaminant and was observed in previous short-term studies to produce lesions in the liver, thyroid and testes of male rats. The present study was undertaken to confirm those observations and to determine the effects after a longer period of exposure. Male rats were fed photomirex for 13 weeks at levels of 0.20, 1.0, 5.0, 25 and 125 ppm in the diet. Deaths were observed in animals receiving the highest dose. Decreased body weight gain and food intake were also observed in that group. Liver weights were increased at 5.0 ppm photomirex and higher. Photomirex caused changes in several biochemical parameters including serum sorbitol dehydrogenase and hepatic aniline hydroxylase activities. Dose-related histological abnormalities were observed in the thyroid and liver starting at the lowest dose level. These results confirm earlier findings and show that photomirex is a potent hepato- and thyrotoxin.

Biological observations from feeding heated corn oil and heated peanut oil to rats

Five groups of male weanling rats were provided purified diets containing 15% by weight of either fresh or laboratory-heated corn oil (FCO, HCO) or fresh, laboratory-heated, or commercial pressure deep-fry peanut oil (FPO, HPO, PPO). Total weight gain, feed consumption, and feed efficiency were consistently greater for the FCO, FPO, and PPO groups. Although relative heart weights were unaffected, the HCO and HPO produced elevated liver and kidney weights. The dietary fats had no effect on the hematological status of the animals or the proportions of cells comprising the total leukocytes of the blood. Physical, chemical, and microscopic evaluation of the urine detected no pathologic conditions. Rats fed diets containing HCO or HPO demonstrated toxicity of thermally oxidized fats by the appearance of diarrhea, dermatitis, seborrhea, and hair loss. Histological examinations revealed injury of the thymus by all fat samples except the FCO; the liver was damaged by the HCO, HPO, and PPO, and the testes and epididymides by HPO and PPO. In the latter case there was complete cessation of spermatogenesis.

Toxicological response and its reversibility in rats fed Lake Ontario or Pacific coho salmon for 13 weeks

Lake Ontario coho salmon were known to contain a mixture of chemical contaminants. A previous study demonstrated that rats fed the Lake Ontario fish-supplemented diet for 28 days exhibited mild biochemical and histological changes. The purpose of the present study was to determine the effects due to a longer term of exposure and the reversibility of these effects. Growth rate and food consumption were not affected by feeding the animals with Lake Ontario or Pacific fish-supplemented diets for 13 weeks. No deaths were observed. Decreased spleen weights were observed in groups of males fed 1.45%, 5.8% Lake Ontario and 2.9% Pacific diet. After a 13 week recovery the spleen weights returned to normal. Decreased serum potassium was observed in male rats fed 2.9% Lake Ontario diet, and all levels of Pacific diet for 13 weeks, and was not evident following maintenance on normal diet. Serum glucose was not affected by the 13-week period of treatment, however; a reduction in this parameter occurred in male rats fed the two highest doses of Lake Ontario diet and all doses of Pacific diet following the 13-week recovery period. Minor hematological changes occurred only in the male rats fed either Lake Ontario or Pacific diet following a 13 week recovery period and included reduced marrow myeloid cells and myeloid/erythroid ratio. Hepatic microsomal ethoxyresorufin deethylase activity was significantly increased in rats ingesting Lake Ontario diet. Mild histological changes occurred in the liver and thyroid of the treated males, and in the liver and kidney of the treated females. These changes were attributed to the chemical residues and/or the fish diet. Data presented here indicated that the Lake Ontario fish-supplemented diet can cause mild biochemical, hematological and histological changes but most of these were reversible when exposure was terminated.

Oral toxicity of malonaldehyde: a 90-day study on mice.

The oral toxicity of malonaldehyde (MA), a product of lipid peroxidation found in some foods, was investigated in a 90-d study on mice, MA as the sodium enol salt was administered in the drinking water to 8-wk-old female Swiss mice at levels calculated to provide 2, 10, 50, 250, or 500 micrograms/g body weight . d. There was no mortality and all groups gained weight at comparable rates except that those that received 500 micrograms/g body weight . d gained more slowly and lost weight after 50 d. Histopathological examination of 27 tissues indicated that the liver was the only organ that underwent dose-dependent changes. All levels of MA induced irregularities (anisokaryosis, hyperchromicity, vesiculation) of hepatic nuclei. Pancreatic lesions consisting primarily of atrophy of the exocrine cells with loss of zymogen granulation occurred in animals which received 500 micrograms MA/g body weight . d. Mild dysplasia of the urinary bladder epithelium was found in all treatment groups. Approximately 1% of the dose was excreted unchanged in the urine at each level of administration.

Toxicological evaluation of malonaldehyde: A 12‐month study of mice

The chronic toxicity of malonaldehyde (MA) was evaluated using Swiss female mice. Beginning at 10 wk of age, MA was administered in the drinking water for 12 mo to groups of 50 animals at levels of 0.1, 1, and 10 micrograms/g body wt.d with 100 controls. The highest dose was associated with increased mortality (28% versus 12-14%). MA had no effect on body weight, organ weight, hematological indices, or the incidence of lesions in 27 tissues examined. More liver lesions were observed in the three treatment groups than in the controls (p less than 0.05), and the histopathologic scores for severity of lesions were significantly increased in the groups that received the two higher levels of MA. The liver lesions included anisokaryosis, changes in cytoplasmic volume with architectural derangements, necrosis and neoplastic changes (nodular hyperplasia, hepatoma, and hemangioma). There was no significant increase in specific neoplasms in the treated groups, but the incidence of total neoplasms and neoplastic lesions was dose-dependent (4%, 8%, and 12%, respectively) (p less than 0.01). There was only one neoplasm (a hemangioma) among the controls (1%). Three animals (6%) given the highest dose of MA developed stomach neoplasms. In terms of human dietary exposure to MA, the lowest level of MA used in this study is about 10 times the estimated average daily intake of MA by the Canadian population on a body weight basis.

Short-term toxicity of photomirex in the rat

Abstract When photomirex (8-monohydromirex) was fed to rats at dietary levels of 0, 0.5, 5.0, 50, or 500 ppm, all 10 animals receiving the highest dose levels died within 7 days, and two of 10 animals in the 50-ppm group died after 24 days. All other animals (10 per group) survived until the experiment was terminated at 28 days. Animals receiving 50 ppm showed decreased body weight gain and food consumption. Liver hypertrophy and increased microsomal enzyme activity (aniline hydroxylase) were observed in groups of animals receiving 5.0 ppm and greater. Serum sorbitol dehydrogenase activity was increased in animals receiving 5.0 ppm and greater. Photomirex accumulated in all tissues examined, with fat and liver having the highest residues. Histological alterations were observed in the liver at 0.5 ppm and consisted of mild midzonal cytoplasmic enlargement. At a level of 5 ppm, the midzonal cytoplasmic enlargement was more pronounced and was accompanied by mild anisokaryosis and nuclear hyperchromicity. At the highest dose, these alterations were accompanied by perivenous fatty infiltration. Lesions of the thyroid were observed in the group of animals receiving 50 ppm (6.61 mg/kg/day) and consisted of a generalized reduction in follicle size and colloid density. Animals which died showed pronounced thyroid follicular atrophy accompanied by severe colloid depletion and epithelial exfoliation. Animals receiving 50 ppm also had lesions in the testes consisting of a mild to marked reduction in spermatogonia and complete cessation of spermatogenesis.

Comparative toxicity of 1,2,3,4-, 1,2,4,5-, and 1,2,3,5-tetrachlorobenzene in the rat: results of acute and subacute studies

Groups of 10 male and 10 female rats were dosed orally with 1,2,3,4-, 1,2,4,5-, or 1,2,3,5-tetrachlorobenzene (TCB) at levels that ranged from 200 to 4000 mg/kg, and were observed clinically for 14 d. LD50 values for 1,2,3,4-, 1,2,4,5-, and 1,2,3,5-TCB were found to be 1470, 3105, and 2297 mg/kg, respectively, in male rats. In females, the LD50 values were found to be 1167 and 1727 mg/kg 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, groups of 10 males and 10 females 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 d. No deaths or clinical signs of toxicity were observed, and neither growth rate nor food consumption was affected. 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 and ethoxyresorufin deethylase were 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. Tissue residue data showed that 1,2,4,5-TCB accumulated at much higher levels than the other two isomers. The results suggest that the position of chlorine substitution can affect the tissue accumulation and toxicity of chlorinated benzenes in rats.

Alterations in Humoral Immune Response to Bovine Leukaemia Virus Antigens in Cattle with Lymphoma

Sera collected from cattle with enzootic bovine lymphoma (EBL) were compared to sera from clinically normal bovine leukaemia virus (BLV)-infected cattle for immunoglobulin concentration and for antibodies detecting BLV proteins tested using three different viral isolates. Monoclonal antibodies to bovine immunoglobulin isotypes were used in Western blot analysis to identify isotype reactivity to specific viral antigens. IgG titres to BLV were determined by ELISA. Serum immunoglobulin (G1, G2 and M) concentrations were assessed by radial immunodiffusion. Although EBL was associated with reduced total immunoglobulin production, sera from cattle with EBL had significantly (P less than 0.001) higher specific IgG titres and produced antibodies against a greater and more varied number of BLV proteins than did sera from clinically normal BLV-infected cattle. Variations were consistent within groups of cattle and did not depend on the viral isolate used.