Search PubMed⌕ Search

Biomedical subjects

K M Abdo

Publications and source records attributed to K M Abdo.

33 records · Page 2Linked to original sources
PubMed1985

Benzyl acetate carcinogenicity, metabolism, and disposition in Fischer 344 rats and B6C3F1 mice.

Carcinogenesis studies of benzyl acetate (a fragrance and flavoring agent) were conducted in F344 rats and B6C3F1 mice. The chemical was given in corn oil by gavage once daily, 5 days/week for 103 weeks, to groups of 50 animals of each sex and species. For rats the doses were 0, 250, and 500 mg/kg body weight and for mice the doses were 0, 500, and 1000 mg/kg. Mean body weights of control and dosed rats and mice were not affected adversely by benzyl acetate. The survival of control and low dose female mice was lower than that of the high dose group. A genital tract infection may have contributed to the reduced survival. No other significant difference in survival was observed for dosed rats or mice. Benzyl acetate was absorbed from the gastrointestinal tract of rats and mice, with approximately 90% of the administered dose recovered as various metabolites in the urine within 24 h. The primary metabolite was hippuric acid, with minor amounts of a mercapturic acid, and one or more unidentified metabolites. This capacity for absorption, metabolism, and disposition was unaffected by the amount or number of doses administered. Under the conditions of these studies, benzyl acetate administration was associated with an increased incidence of acinar cell adenoma of the exocrine pancreas in male F344/N rats. No evidence of carcinogenicity was found for female F344/N rats. For male and female B6C3F1 mice there was evidence of carcinogenicity, in that benzyl acetate caused an increased incidence of hepatocellular neoplasms (particularly adenomas) and squamous cell neoplasms of the forestomach.

Absorption↗
PubMed1984

Toxicity of hexachlorocyclopentadiene: subchronic (13-week) administration by gavage to F344 rats and B6C3F1 mice.

A 13-week subchronic study was conducted by administering hexachlorocyclopentadiene ( HCCP ) in corn oil by gavage to groups of ten male and ten female F344 rats at doses of 150, 75, 38, 19, 10 or 0 mg kg-1, and to groups of ten male and ten female B6C3F1 mice at doses of 300, 150, 75, 38, 19 or 0 mg kg-1. The doses were administered once a day, five days per week for 13 weeks. Chemically induced deaths occurred at 150 and 300 mg kg-1 in rats and at 300 mg kg-1 in mice. A significant (P less than 0.05) depression in mean body-weight change relative to controls was observed in male and female rats receiving greater than or equal to 38 and greater than or equal to 75 mg kg-1, respectively, and in male and female mice receiving 150 and 300 mg kg-1, respectively. There was a significant (P less than 0.05) increase in liver and kidney weight: brain weight ratios in the high-dose female rats (75 and 150 mg kg-1) and female mice at all doses (19-300 mg kg-1). HCCP caused proliferative and inflammatory changes of the epithelia in the forestomach of male rats, and male and female mice receiving greater than or equal to 38 mg kg-1 and in female rats receiving greater than or equal to 19 mg kg dose level. Nephrosis characterized by proximal tubular dilation, cytoplasmic vacuolization, cytomegaly, karyomegaly and anisokaryosis occurred in male and female rats and female mice receiving greater than or equal to 38 mg kg-1.

Animals↗
PubMed1984

Chronic kidney disease and organic chemical exposures: evaluations of causal relationships in humans and experimental animals.

Chronic renal failure is a serious health problem in the United States and other developed countries, and large amounts of public funds are being expended for what is essentially palliative treatment of this disease. Historical data also indicate increasing trends for urinary tract cancers of both sexes in the United States. Although the data on humans are not definitive, causal associations appear to exist between occupational exposures to some hydrocarbon solvents and chronic kidney disease, and there is preliminary evidence that suggests an association between organic chemical exposures and cancers of the urinary tract in humans. A review of more than 230 chemicals tested in two-year chronic toxicity studies by the National Toxicology Program (NTP)/National Cancer Institute (NCI) has identified two chemical classes that commonly produced nonneoplastic chronic renal disease in rodents: aromatic amines and organohalides. Tumors of the kidney were most frequently produced by alkyl or alkenyl halide compounds, while tumors of the bladder were caused by aromatic amines. Consistent with many literature reports, short-chain halogenated hydrocarbons appeared to have a propensity for causing a low incidence of renal tubular carcinoma in exposed rodents. Comparative analyses of the NTP/NCI studies did not indicate consistent sex or species differences in the nonneoplastic chronic toxic response, but chemically induced urinary tract cancers occurred more commonly in rats than in mice, and chemically induced cancers of the kidney occurred more commonly in males than in females. Viewed collectively, these data indicate a potential for organic chemicals, especially halogenated hydrocarbons and aromatic amines, to produce chronic kidney injury in humans and other mammalian species.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Absence of carcinogenic response in F344 rats and B6C3F1 mice given D-mannitol in the diet for two years.

Diets containing 2.5 or 5% D-mannitol were fed to groups of 50 F344 rats and 50 B6C3F1 mice of each sex for 103 wk. Similar groups served as controls. There were no significant differences in survival between treated and control rats or between treated and control mice. Mean body weights were similar in treated and control male rats and in treated and control female mice. Throughout the study, the mean body weights of female rats on the 5% diet were slightly (less than 10%) lower than those of the controls, and by the end of the study the mean body weights of treated male mice were slightly (c. 10%) higher than those of the controls. Feed consumption by treated and control animals was approximately the same in rats and mice of either sex. The incidence of dilation of the gastric fundal gland was higher (46%) in treated female rats than in the controls (12%). A mild nephrosis, characterized by focal vacuolization of the renal tubular epithelium, showed an increased incidence in treated mice of both sexes and was considered to be related to the administration of D-mannitol. There were no statistically significant increases in tumour incidence in any of the treated groups when compared with the corresponding controls. Under the conditions of this bioassay, D-mannitol was not shown to be carcinogenic for F344 rats or B6C3F1 mice of either sex.

Animals↗
PubMed1983

Effect of subchronic dermal application of O-ethyl O-4-nitrophenyl phenylphosphonothioate on producing delayed neurotoxicity in hens.

Daily dermal administration for 90 days of 0.01 to 10 mg/kg of O-ethyl O-4-nitrophenyl phenylphosphonothioate (EPN) technical grade (85%) in acetone (0.1 ml) on the unprotected back of the neck produced delayed neurotoxicity. Hens given 2.5 to 10 mg/kg daily doses also received daily doses of atropine sulfate for 5 or 6 days to protect against cholinergic acute toxicity. Severity of the clinical condition depended on the concentration of the daily dermal dose of EPN; i.e., while hens given small doses showed only ataxia, those treated with large doses progressed to paralysis and died. The most consistent histopathologic alteration was the degeneration of axons and myelin in the spinal cord which was identical to that found in positive control hens that received daily dermal doses of 5 or 10 mg/kg tri-o-cresyl phosphate (TOCP). Some of the hens treated daily with the smallest tested dose of EPN (0.001 mg/kg) which did not show clinical signs of delayed neurotoxicity showed equivocal histological changes in the spinal cord. EPN and TOCP treatments had a more profound effect on the activity of plasma butyrylcholinesterase than that of brain acetylcholinesterase (AchE). by contrast O,O,-diethyl O-4-nitrophenyl phosphorothioate (parathion) was more inhibitory to brain AChE. Negative control hens that were treated with 90 daily dermal doses of 1 mg/kg of parathion initially showed leg weakness followed by recovery. A group of hens that received the same volume of acetone (0.1 ml) daily remained normal.

Animals↗
PubMed1982

Neurotoxicity of continuous (90 days) inhalation of technical grade methyl butyl ketone in hens.

Neurotoxicity was produced in 1-yr-old hens (five hens per treatment) by continual 90-d exposure in inhalation chambers to atmospheres containing 50, 100, 200, or 400 ppm technical grade methyl butyl ketone (MBK) containing 70% methyl n-butyl ketone (MnBK) and 30% methyl isobutyl ketone (MiBK). A 30-d observation period followed. Severity of clinical condition and progression or improvement of neurological deficit signs were dependent on the concentration of MBK and duration of exposure. Hens exposed to the two highest levels developed ataxia and paralysis; they died or were sacrificed before the designated exposure period ended. The intermediate level of MBK (100 ppm) caused severe ataxia; most treated hens showed no change in clinical condition during the observation period. Hens exposed to 50 ppm exhibited gross ataxia, with most demonstrating partial regression of neurological deficit after the exposure ceased. Hens exposed to the lowest tested level (10 ppm) remained normal. Only hens exposed to 400 or 200 ppm showed significant weight loss. Some hens from the 50-400 ppm treatment groups showed unequivocal histopathologic changes in the spinal cord and peripheral nerves. Severity of histopathologic changes depended on the level and duration of MBK exposure. These changes were characterized by excessive swelling, phagocytosis, degeneration, and demyelination of the axons.

Animals↗
PubMed1979

Delayed neurotoxic, late acute and cholinergic effects of S,S,S-tributyl phosphorotrithioate (DEF): subchronic (90 days) administration in hens.

Subchdronic administration of S,S,S-tributyl phosphorotrithioate (DEF) caused 3 toxicologic effects in hens, depending upon route of administration. Small delay oral doses (0.5--20 mg/kg) of DEF produced ataxia, which progressed to paralysis and death in some birds. Large daily oral doses (40 and 80 mg/kg) caused a 'late acute' effect 4 days after administration. The clinical signs of the late acute effect were identical to those produced by n-butyl mercaptan (nBM), a hydrolytic product of DEF, and were not relieved by atropine sulfate. The late acute effect of DEF overlapped with the clinical signs of delayed neurotoxicity. These hens died early, and while one hen showed histopathological lesions in peripheral nerves, another showed unequivocal lesions in the central nervous system. Topical application of daily doses of DEF consistently produced delayed neurotoxicity in the absence of late acute poisonining and was characterized by degeneration of the central and peripheral nerve tissues. Orally administered DEF was rapidly metabolized in the gastrointestinal tract to nBM, which apparently caused the late acute toxic effect. Topically administered DEF, which was not subjected to gastrointestinal tract hydrolysis, caused delayed neurotoxicity but did not produce a late acute effect.

Animals↗
PubMedDate not supplied

Thirteen-week toxicity study of d-alpha-tocopheryl acetate (vitamin E) in Fischer 344 rats.

A 13-wk study was conducted by administering d-alpha-tocopheryl acetate (vitamin E) in corn oil by gavage to groups of ten male and ten female Fischer 344 rats at doses of 0, 125, 500 or 2000 mg/kg body weight daily for 13 wk. The dose of corn oil given was 3.5 ml/kg. Additional groups of ten males and ten females were included and served as untreated controls. Deaths occurred only in males at 2000 mg/kg. Vitamin E dosing had no effect on body weight or food consumption. The liver-to-body weight ratio of females at 2000 mg/kg was significantly increased. In males, high levels of vitamin E (2000 mg/kg) caused prolongation of both prothrombin and activated partial thromboplastin (APTT) times, reticulocytosis and a decrease in haematocrit values and haemoglobin concentrations. APTT was also lengthened in females at this dose level. High levels (2000 mg/kg) caused haemorrhagic diathesis in both males and females and increased medullary erythropoiesis in the spleen of one male. Vitamin E at all doses tested caused interstitial inflammation and adenomatous hyperplasia of the lung. The above findings indicate that vitamin E administration in excessive amounts is potentially toxic.

Administration, Oral↗
PubMedDate not supplied

No evidence of carcinogenicity of D-mannitol and propyl gallate in F344 rats or B6C3F1 mice.

Chronic toxicity and carcinogenicity studies were conducted on D-mannitol and propyl gallate in F344 rats and B6C3F1 mice. Groups of 50 rats and 50 mice of each sex were maintained on diets containing either 0, 2.5 or 5.0% D-mannitol or 0, 0.6 or 1.2% propyl gallate for 103 wk. D-Mannitol had no effect on survival or mean body weight of rats and mice, and feed consumption was approximately the same in control and treated groups in each species. Gastric fundal gland dilation occurred at a higher incidence in treated female rats than in controls. A mild nephrosis characterized by focal vacuolization of the renal tubular epithelium was observed in an increased incidence in treated mice. No significant increase in tumour incidence was observed in any of the treated groups in comparison with the corresponding controls. Survival of rats and mice given propyl gallate was similar to that of the controls. Mean body weights were lower in chemically exposed animals, and more so for females. Male rats exposed to propyl gallate showed an increased incidence of hepatic cytoplasmic vacuolization and suppurative inflammation of the prostate gland. Tumours of the preputial gland, islet-cell tumours of the pancreas, and phaeochromocytoma of the adrenal gland occurred at a significantly (P less than 0.05) higher incidence in the low-dose male rats. Malignant lymphoma occurred with a positive trend in male mice (control 1/50, low dose 3/49 and high dose 8/50), and the incidence in the high-dose group was significantly (P less than 0.05) higher than in the control group. However, since the incidence in the control group was much less than the historical control rate (36/398 or 9%) in this laboratory, this apparent increase was not considered to be related to propyl gallate administration. Under the conditions of these studies, neither D-mannitol nor propyl gallate was considered to be carcinogenic to F344 rats or B6C3F1 mice of either sex.

Administration, Oral↗
PubMedDate not supplied

Carcinogenesis bioassay in rats and mice fed diets containing 2-biphenylamine hydrochloride.

Diets containing 0.1 or 0.3% 2-biphenylamine hydrochloride were fed to groups of 50 Fischer 344 rats and 50 B6C3F1 mice of each sex for 104-106 weeks. Mean body weights of high-dose rats of both sexes and of low-dose male rats were slightly lower than those of controls. No significant differences in survival times were observed between dosed and control groups. In dosed male rats there was a compound-related increased incidence of kidneys with inflammatory cells and interstitial fibrosis. No tumors in dosed rats were associated with the chemical. Mean body weights of high-dose male mice were slightly lower than those of controls, and survival of high-dose male mice was also significantly (P less than 0.01) reduced relative to controls. Hemangiosarcoma of the circulatory system occurred in female mice with a statistically significant (P less than 0.001) positive trend. The observed incidences of hemangiosarcoma were 0/49 (0%), 1/50 (2%), and 7/50 (14%) in controls, low- and high-dose groups, respectively. In individual group comparisons, the incidence in the high-dose group was significantly (P less than 0.01) higher than that in the controls. The hemangiosarcoma seen in female mice were quite rare with only 6/816 (0.7%) previously seen in controls at the same laboratory and no more than 3 in any group of 50. Hemangiosarcoma also occurred in male mice with a statistically significant positive trend (P = 0.04 by a life table test), with incidences of 0/50 (0%), 2/50 (4%), and 3/50 (6%), in control, low-dose and high-dose groups, respectively. The development of hemangiosarcoma in the high-dose male mice might have been curtailed by the significantly reduced survival time in this group.

Aminobiphenyl Compounds↗
PubMedDate not supplied

Heinz body production and hematological changes in the hen after administration of a single oral dose of n-butyl mercaptan and n-butyl disulfide.

n-Butyl mercaptan (nBM) is a breakdown product of S,S,S,-tri-n-butyl phosphorotrithioate (DEF) and S,S,S-tri-n-butyl phosphorotrithioite (merphos) in hens and in the environment. n-Butyl disulfide (nBD) is an oxidation product of nBM. A single 500 mg/kg dose of nBM and nBD was administered in gelatin capsules to groups of five 12-month old laying hens. A third group (five hens) was given gelatin capsules. One day after administration, the hens exhibited weakness which progressed to unsteadiness and inability to stand by the third day. These signs were accompanied by a pale comb 18--24 hr after dosing, which changed to dark color at 48 hr. Treated hens improved with time. Heinz bodies and extensive erythrocyte deformation and lysis were observed in blood smears taken from hens 24 and 48 hr after treatment. Hemoglobin concentration, packed cell volume, erythrocytes, and glucose-6-phosphate dehydrogenase activity were significantly lower than controls, while methemoglobin was significantly higher. As the clinical condition of these hens improved, these hematologic changes disappeared. nBM caused an initial increase in plasma butyrylcholinesterase activity which was dose-dependent and returned to normal by the end of the 28-day experiment. Also, brain acetylcholinesterase activity was not different from that of the control at termination.

Animals↗
PubMedDate not supplied

Glycine modulates the toxicity of benzyl acetate in F344 rats.

The influence of supplemental glycine on benzyl acetate (BA; a compound metabolized via the hippurate pathway)-induced toxicity was investigated. Groups of male F344 rats were fed NIH-07 diet containing 0, 20,000, 35,000, or 50,000 ppm BA for up to 28 days. Two additional groups were fed NIH-07 diet with 50,000 ppm BA and 27,000 ppm glycine or 50,000 ppm BA 32,000 ppm L-alanine; supplemental glycine and L-alanine were equimolar. The L-alanine group served as an amino nitrogen control. A third group was fed NIH-07 diet with 32,000 ppm L-alanine and served as an untreated isonitrogenous control BA caused increase in mortality, body weight loss, the incidence of abnormal neurobehavioral signs such as ataxia and convulsions, along with astrocyte hypertrophy and neuronal necrosis in the cerebellum, hippocampus, and pyriform cortex of the brain. These effects were reduced significantly by supplementation with glycine but not with L-alanine. These results suggest that the neurodegeneration induced by BA is mediated by a depletion of the glycine pool and the subsequent excitotoxicity.

Air Pollutants, Occupational↗
PubMedDate not supplied

Subchronic toxicology studies of hexachloro-1,3-butadiene (HCBD) in B6C3F1 mice by dietary incorporation.

Two-week repeated-dose and 13-week subchronic studies of HCBD were conducted in B6C3F1 mice. Groups of five mice/sex received 0, 30, 100, 300, 1,000, or 3,000 ppm HCBD in feed for 15 days. Toxic responses, primarily in the higher dose groups, included abnormal clinical signs (lethargy, hunched posture, rough coat, sensitivity to light, and/or incoordination), mortality (all mice in the top two dose groups died by day 7), body and organ weight depression, and gross and histopathological changes. The most prevalent microscopic lesion, seen in all HCBD-treated mice of both sexes, was renal tubular cell necrosis and/or regeneration. Regeneration was seen only in the lower dose groups. Thirteen-week studies were conducted in which groups of 10 mice/sex received 0, 1, 3, 10, 30, or 100 ppm HCBD in feed. No treatment-related clinical signs or mortality were observed. Body weight gain was reduced in the 30- and 100-ppm males (-49 and -56, respectively), and the 100-ppm females (-47). Significant reduction in kidney weights was seen in the 30- and 100-ppm males and 100-ppm females. A treatment-related increase in tubular cell regeneration in the renal cortex occurred in both male and female mice. This lesion was characterized by an increase both in number and basophilic staining intensity of the tubular epithelial cells. Regeneration was seen in the outer stripe of the outer medulla and extended into the medullary rays (pars recta); severity increased with dose. Female mice were more susceptible to the toxicity of HCBD than male mice. Although no adverse effects were observed at the 10-ppm level for male mice in the subchronic study, the regenerative lesion was present in female mice at 1 ppm, the lowest dose administered.

Animals↗
PubMedDate not supplied

Physiological disposition and metabolism of O-ethyl-O-4-nitrophenyl phenylphosphonothioate in male cats following a single dermal administration.

The pharmacokinetics and metabolism of a single dermal 20.0 mg/kg of uniformly phenyl-labeled [14C]EPN (O-ethyl O-4-nitrophenyl [14C]phenylphosphonothioate) were investigated in adult male cats. Three treated cats were killed at each time interval: 0.5, 2, 4, 8, and 12. Radioactivity disappeared exponentially from administration site at a rate constant of 0.46 day-1, corresponding to a half-life of 1.5 days. Most of the absorbed radioactivity was excreted in the urine (29.9%). Only 3.2% of the 14C was recovered in the feces. No radioactivity was detected in expired CO2. Only traces of EPN were detected in the urine and feces. Most of the excreted 14C materials were identified as O-ethyl phenylphosphonothioic acid (EPPTA), O-ethyl phenylphosphonic acid (EPPA), and phenylphosphonic acid (PPA). The disposition studies showed that EPN was the major compound identified 0.5 day after administration in the brain, spinal cord, sciatic nerve, adipose tissue, plasma, muscle, liver, and kidney. Most of the radioactivity in the liver and kidney was identified after 4 days as EPPTA, EPPA, and PPA. Kinetic and distribution studies showed that EPN was eliminated from the tissues and plasma according to exponential kinetics. The half-life of the elimination of EPN from plasma was 9.1 days corresponding to a constant rate value of 0.076 day-1. Relative residence (RR) of EPN relative to plasma was longest in the sciatic nerve and shortest in the kidney.

Animals↗