摘要:

Since the rat is frequently the experimental animal of choice for toxicology testing, studies were undertaken to adapt assays routinely used to evaluate immune function in mice so that immune function could likewise be evaluated in collaborative projects employing toxicant‐treated rats. Contrary to previous reports in the literature, Type III pneumococcal polysaccharide (S3) was immunogenic in rats. Specific antibody responses to S3 were demonstrated in two strains of rats following immunization by either the subcutaneous (sc) or intraperitoneal (ip) route with purified S3, with S3 contained in polyvalent pneumococcal polysaccharide vaccine (pneumovax), or with heat‐killed Type III Streptococcus pneumoniae. Dose‐response studies demonstrated that the optimal immunizing dose in Sprague‐Dawley or Fischer rats was 25 μg S3. Reimmunization with S3 on d 21 did not produce an anamnestic response, and the kinetic data were consistent with S3 being a thymus‐independent (T‐independent) antigen in the rat. In contrast to our previous studies in the mouse, concurrent sc or ip injections of pertussis vaccine did not modify the response to S3 in rats. Sprague‐Dawley rats acquired the capacity to respond immunoiogicaiiy to S3 between 24 and 31 d of age. In mature animals, sex had no effect on the ability to respond to S3. The utility of this model as a means of characterize toxicant‐induced immune dysfunction was demonstrated using the prototype immunotoxicant cyclo‐phosphamide.

ISSN:0098-4108    

DOI:10.1080/15287398209530301

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

Ten male Long‐Evans rats were given 20% v/v ethanol in the drinking water for 60 consecutive days. Ten other males were given distilled water and served as controls. Each male was then allowed to mate with three virgin female Long‐Evans rats, once per week for three consecutive weeks. The males were necropsied after the third mating, the females were killed on d 20 of gestation, and the offspring were examined for parameters of fetal growth, skeletal ossification, and soft‐tissue anomalies. Ethanol caused testicular weight reductions and gross testicular atrophy in 1 of 10 males. Five matings of alcoholic male rats proved infertile. Total embryonic deaths (resorptions and preimplantation loss) were increased by ethanol, while implantations and litter size were significantly decreased. Fetuses fathered by alcoholic male rats were malformed: 55% had soft‐tissue anomalies (microcephalus, microphthalmia, cranial fissure, and hydronephrosis). Litter weight and average pups weights were also reduced by paternal ethanol consumption. No recovery in reproductive function was evident over the 21‐d post‐ethanol mating period.

ISSN:0098-4108    

DOI:10.1080/15287398209530302

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

The long term effects of the oral contraceptive, Norlestrin, were evaluated in sexually mature female rhesus (Macaca mulatta) monkeys over a 10 year period. Norlestrin, a combination of norethindrone acetate and ethinyiestradioi (50: 1) was given orally on a continuous cyclic regimen of 21 d of dosing followed by 7 d without treatment Groups of 16 monkeys each received the drug at dose levels of 0.05, 0.51, and 2.55 mg/kg representing multiples of 1, 10, and 50 times the human dose, respectively. A comparable group of 16 animals remained untreated and served as controls. Selected clinical and laboratory parameters were monitored throughout the study and all animals were necropsied and evaluated for gross and histopathologic changes.

ISSN:0098-4108    

DOI:10.1080/15287398209530303

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

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 μg/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 < 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 < 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.

ISSN:0098-4108    

DOI:10.1080/15287398209530304

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

O‐n‐Propyl O‐(2‐propynyl) phenylphosphonate (NIA‐16388), which has been recommended for use as insecticide synergist, was synthesized and tested for acute and neurotoxicities in hens. The 24‐h LD50 value of this compound in the hen was found to be about 340 mg/kg. Hens treated with this compound at 400 mg/kg with atropine sulfate as an antidote developed clear clinical signs of delayed neurotoxicity 12–17 d after single oral treatment. The signs of neurotoxicity gradually progressed from ataxia through paralysis. Biochemical tests indicated that at the tested dose level of this compound, the level of hen‐brain neurotoxic esterase (NTE) was inhibited in vivo to less than 10% of the normal level 1 d after treatment. These clinical and biochemical signs of neurotoxicity are supported by histopathological findings. Degenerative lesions of axons were observed in the N1A‐treated group of hens. The lesions in the spinal cord were seen most frequently and most prominently in the lateral columns, although they sometimes were observed in other areas, e.g., in the anterior columns (especially in thoracic and lumbar sections). Generally, the lesions were more apparent in the longitudinal sections than in the cross‐sections. Two other phenylphosphonate derivatives, O‐ethyl S‐benzyl phenylphosphonothioate (ESBP) and O‐methyl O‐(4‐benzylidenylphenylhydrazone) phenylphosphonothioate, were also synthesized and tested for neurotoxicity to hens. The LD50 values for these two compounds in the hen were more than 1000 mg/kg. No signs of delayed neuropathy were detected in hens given either ESBP or the hydrazone compound at single oral doses of 1000 mg/kg.

ISSN:0098-4108    

DOI:10.1080/15287398209530305

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

Adult cricket frogs (Acris crepitans) were held, individually for 96 h in static systems containing initial concentrations of either 0, 0.1, 7.0, or 10 ppm parathion in 10 ml water. Mortality of cricket frogs was directly related to the parathion concentration in the water. Frogs from the 1.0‐ and 10‐ppm groups accumulated 0.08 and 4.6 ppm parathion, respectively. One of four American kestrels (Falco sparverius) fed frogs from the 10‐ppm group died from organophosphate poisoning less than 3 h after consuming five frogs. Mortality did not occur in kestrels fed frogs from the other treatment groups, which represented more environmentally realistic levels of exposure.

ISSN:0098-4108    

DOI:10.1080/15287398209530306

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

Female European ferrets (Mustela putorius furo) absorbed 98.5% of a single dietary exposure of hexachlorobenzene (HCB). The HCB was found to readily cross the placenta and to be excreted in the milk of pregnant/lactating ferrets. A fter consuming HCB‐treated feed, ferrets raising offspring excreted 50% of the initial dose by 32 d, while unbred ferrets achieved this same degree of HCB elimination in 41 d. The percentages of HCB excreted via the urine and feces were approximately 5 and 45%, respectively, in both groups at the 50% stage of elimination. Adipose tissue was the most significant long‐term repository for HCB in the ferret. The other tissues analyzed for [14C]HCB showed a general relationship of increased radioactivity with increased fat content of the tissue. The ferrets with nursing hits were able to significantly reduce their body burden of HCB when compared to unbred females. The developing ferret kits were subjected to HCB insult both in utero and via dam's milk. The ratio of milk to placental exposure in the growing offspring was calculated to be 31: 1. Thus, in addition to any toxic effects HCB may have on the adult reproducing population, the placental and mammary transfer of HCB constitutes a potential threat to the developing and growing animal.

ISSN:0098-4108    

DOI:10.1080/15287398209530307

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

The pathogenesis and factors affecting hydrazine‐induced fatty liver have been investigated in rats using histological and ultrastructural examination. A dose of 20 mg hydrazine/kg caused the accumulation of lipid, swelling of mitochondria, and the appearance of microbodies in both periportal and midzonal hepatocytes and in the proximal tubular cells of the kidney. These changes were detectable by light or electron microscopy 24 h after dosing with hydrazine. A dose of 60 mg/kg was the highest dose tolerated for 24 h, but the severity of the fatty liver was similar to that after a dose of 40 mg/kg. The accumulation of lipid droplets and the swelling of mitochondria were detectable by electron microscopy 30 min after dosing, but the accumulation of fat could not be detected by light microscopy until 4 h after dosing. Pretreatment of animals with phenobarbital or piperonyl butoxide respectively reduced and increased the severity of the fatty liver. Pyruvate azine was much less toxic than the parent hydrazine on a molar basis, although some fatty vacuolation was detectable in midzonal hepatocytes.

ISSN:0098-4108    

DOI:10.1080/15287398209530308

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

Hydrazine causes a dose‐related increase in liver triglycerides and in liver weight and causes a decrease in hepatic giutathione. The threshold dose for the toxic effect is around 10 mg/kg, and the optimal effect is seen after a dose of 40 mg/kg. The effect of hydrazine on liver weight and glutathione was detectable within 30 win of dosing, but the elevation of hepatic triglycerides was not detectable until 4 h after dosing. At 24 h after a dose of 60 mg hydrazine/kg, hepatic reduced giutathione was approximately 50% of the control value and triglycerides were about 7 times the normal level. In vitro studies indicated that hydrazine is metabolized by rat liver microsomal enzymes, this being dependent on NADPH and oxygen. Pretreatment of animals with phenobarbital or piperonyl butoxide respectively decreases and increases the hepato‐toxicity. Prior depletion of hepatic giutathione by administration of diethyl maleate had no effect on the toxicity. Pyruvate azine, a probable metabolite of hydrazine, is much less toxic than hydrazine itself on a molar basis. These and other results suggest that although hydrazine is metabolized via several routes, the hepatotoxicity may well be due to the parent compound rather than a metabolite.

ISSN:0098-4108    

DOI:10.1080/15287398209530309

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor

摘要:

Rats were nose‐exposed to an atmosphere containing gaseous [14C] acrylic acid for 7 min and sacrificed 1.5 and 65 min later. At 1.5 min 28% of the administered radiolabel was associated with the snout of the exposed animal. The biodistribution data indicated the gastrointestinal tract as the major site of absorption of acrylic acid after inhalation exposure. ThereforeJunrats were also stomach intubated with an aqueous solution of f[11C]acrylic acid and sacrificed at 1.5, 10, 20, 40, and 65 min after intubation. The absorption of acrylic acid from the stomach was rapid, as was its subsequent metabolism. Carbon‐11 was rapidly eliminated from both nose‐exposed and stomach‐intubated animals as11CO2, with about 60% of the administered dose eliminated 1 h after administration. A portion of the radiolabel was also eliminated via the renal system.

ISSN:0098-4108    

DOI:10.1080/15287398209530310

出版商:Taylor & Francis Group    

年代:1982

数据来源: Taylor