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Biomedical subjects

D J Ecobichon

Publications and source records attributed to D J Ecobichon.

At least 37 records · Page 2Linked to original sources
PubMed1986

A subchronic inhalation toxicity study of a Matacil formulation in the albino rat.

The subchronic toxicity of a new formulation of Matacil (aminocarb) was assessed by exposing male and female Sprague-Dawley rats via a nose-only technique to a respirable (2.0- to 4.1-microns diameter) aerosol at chamber concentrations of 22.5, 45, and 90 micrograms of insecticide/liter of air for 2 hr/day for 30 consecutive days. Control groups were exposed to a vehicle aerosol or to room air. Randomly selected rats of each group were bled after 8, 15, and 30 days of treatment, and after a 30-day recovery period. Routine clinical laboratory investigations (hematology, blood chemistry, and urinalysis) were conducted during treatment. Other parameters measured included body weight, feed intake, plasma, red blood cell count, brain cholinesterase activity, and hepatic and renal carboxylesterase activities. Organ weights were recorded at necropsy and routine histopathological evaluation was performed. Mild muscle tremors were observed occasionally in the intermediate- and high-dose groups. Treated females, but not males, demonstrated a dose-dependent inhibition of cholinesterase activity, though within treatment groups, there were no differences associated with the number of days of treatment. Enzyme values had returned to baseline levels by 30 days post-treatment. Hepatic carboxylesterase activity was significantly reduced only in male rats at the highest dose. Lung weights were increased in vehicle and Matacil-treated groups. Histological studies indicated that these changes were a nonspecific tissue response to a heavy burden of an oil-based irritant, which was partially resolved by 30 days post-treatment. The results showed that, at the concentrations tested, the formulation produced little or no acute symptoms and minimal long-term sequellae.

Acetylcholinesterase↗
PubMed1986

An assessment of the neurotoxic potential of fenitrothion in the hen.

The potential of single, toxic doses of fenitrothion (O,O-dimethyl O-(4-nitro-m-tolyl)phosphorothioate) to elicit delayed neurotoxicity in the adult White Leghorn hen was compared to the effects produced following similar treatment with the known neurotoxin, tri-o-tolyl phosphate (TOTP). Hens (2.0-2.5 kg body wt) received single oral doses of fenitrothion (500 mg/kg) or TOTP (500 mg/kg), the resulting toxicity being assessed by measuring biochemical (brain and spinal cord acetylcholinesterase (AChE) and neurotoxic esterase (NTE), physiological (motor function) and morphological (cross- and longitudinally-sectioned and stained preparations) parameters of the brains, spinal cords and sciatic nerves of groups (n = 5) of hens at 24 h, 7, 14, 28, 42 and 56 days post-treatment. At 24 h after treatment, fenitrothion caused a marked inhibition of neuronal AChE while TOTP had no effect. In contrast, TOTP caused a significant inhibition of NTE whereas fenitrothion was without effect. At 7 days after treatment, the NTE was still significantly reduced in TOTP-treated hens but normal levels of activity were detected at 14 days post-treatment. No alternation in NTE activity was found in any fenitrothion-treated hens. A characteristic, central-peripheral, distal axonopathy was observed following treatment with TOTP, mild signs appeared 7-14 days post-treatment and increased in severity up to 28 days after treatment, concomitant with morphological changes primarily in the sciatic nerves and spinal cords. Minimal morphological changes were elicited by fenitrothion at this dosage, the tissues appearing no different than those seen in vehicle-treated control hens. The results demonstrated that fenitrothion was distinctly different from TOTP in the biochemical, physiological and morphological effects produced in acutely treated hens and that fenitrothion could not be considered to be neuropathic in the classical manner of TOTP.

Acetylcholinesterase↗
PubMed1986

Acetaminophen in the guinea pig: metabolite identification in blood, urine, and bile.

The biotransformation of single acute oral doses of acetaminophen (100 mg/kg body weight) in adult male guinea pigs was studied by collecting serial blood, urine, and bile samples post-treatment and identifying and quantitating the concentrations of parent drug and excretory products by high performance liquid chromatography. The plasma half-life (beta t/2) (mean +/- SD) of acetaminophen was 1.87 +/- 0.30 h, while that of the only metabolite detected in plasma, the glucuronide, was 2.41 +/- 0.64 h. In 24-h urine samples, the predominant product was the glucuronide (90%) with a small amount of the sulphate conjugate (7.0%) and approximately 3.0% acetaminophen. In bile, the glucuronide was the major metabolite detected initially but, with time, this product decreased concomitantly with an increase in the cysteinyl conjugate. No sulphate was detected in bile but two unidentified metabolites were detected, having distinct column retention times and comprising approximately 6-10% of the total excretory products. The results demonstrated that glucuronidation is a high capacity biotransformation pathway for acetaminophen in this species, only small amounts of other conjugated products being detectable under usual circumstances.

Absorption↗
PubMed1986

Diazepam metabolism in the guinea pig materno-fetal model: effects of cigarette smoke.

The transplacental acquisition, disposition and biotransformation of diazepam (DZ) was investigated in the pregnant guinea pig at 65-67 days of gestation following the administration of single oral doses of 10 mg/kg body weight, the dams and fetuses being euthanized 60 min post-treatment. Tissues (blood plasma, liver, brain, perirenal fat and placenta) were removed for drug residue analysis. Nordiazepam (NDZ) was the only metabolite produced by guinea pigs in vivo. Residues of DZ and NDZ were found in fetal tissues, indicating that the placenta was not an effective barrier. The influence of cigarette smoke on in vitro DZ biotransformation was studied by exposing pregnant guinea pigs (55-57 days of gestation) to ambient air (control) or cigarette smoke thrice daily for 10 consecutive days. At term (day 67), the fetuses were delivered by caesarean section for the preparation of hepatic and placental microsomes to measure the metabolism of DZ. DZ was converted at a slow rate into NDZ by fetal hepatic and placental microsomes in vitro. Exposure to cigarette smoke had no effect on DZ metabolism by the dam liver or by the placenta but a 2-4-fold increase in NDZ formation was observed in fetal hepatic microsomes.

Animals↗
PubMed1984

An acute and subacute neurotoxicity assessment of trichlorfon.

The toxicity of trichlorfon (O,O-dimethyl-2,2,2,-trichloro-1-hydroxyethylphosphonate, Dipterex, Dylox), reported to elicit delayed neurotoxicity in man and chickens, was studied by administering single subcutaneous doses of 100 or 300 mg/kg to adult White Leghorn hens. At 24 h posttreatment, the birds were observed for visible signs of neurotoxicity, were euthanized, and samples of blood plasma, brain, and spinal cord (cervical and thoracic regions) were obtained for quantification of cholinesterase and neurotoxic esterase (NTE) activities. In subacute studies, hens were dosed with trichlorfon (100 mg/kg) every 72 h for a total of six doses. Seventy-two hours after the final dose the hens were euthanized, the brains, spinal cords, and distal sciatic nerves were removed for enzymatic and (or) histological examination. Parallel acute and subacute studies were conducted using diisopropyl phosphorofluoridate (DFP), a known neurotoxic agent, at subcutaneous dosages of 1.0 mg/kg. In the acute studies, both DFP and trichlorfon markedly inhibited tissue cholinesterase activities but only DFP elicited a significant inhibition of NTE. In the subacute studies, DFP produced a characteristic central-peripheral distal axonopathy in the 18-day period of study which was confirmed by clinical and morphological evidence and by marked inhibition of neuronal NTE. Trichlorfon caused little or no obvious neurotoxicity, an observation that was supported by minimal morphological changes and impairment of walking ability and no inhibition of brain or spinal cord NTE.

Animals↗
PubMed1984

The function of motor nerves innervating slow tonic skeletal muscle in hens with delayed neuropathy induced by tri-o-tolyl phosphate.

The reduction of neurogenic posttetanic potentiation in the slow twitch, soleus muscle is an index of impaired motor nerve function in cats with organophosphate-induced neuropathy. We have applied the measurement of posttetanic potentiation to study the functional state of the slow, tonic, plantaris muscle and its motor innervation in adult White Leghorn hens with tri-o-tolyl phosphate (TOTP)-induced neuropathy. At suitable intervals following single oral doses of vehicle or TOTP (500 mg/kg), nerve conduction velocity and posttetanic potentiation were measured in anesthetized hens. Conduction in the sciatic nerve was not altered by TOTP. The plantaris muscle of birds treated with vehicle (peanut oil) either failed to contract or responded to nerve stimulation at 0.4 Hz with very small twitches. Following nerve stimulation at frequencies inducing tetanus (50-140 Hz), the muscles responded with large, slow twitches that gradually decayed in amplitude. The area under the curve formed by the amplitude of these twitches over time (posttetanic potentiation) was directly proportional to the frequency and duration of nerve stimulation. In hens at 1,2, and 4 weeks following treatment with TOTP, the average amount of posttetanic potentiation was reduced concomitantly with the development of ataxia, paralysis, and pathological changes in the peripheral nerves. This difference between vehicle- and TOTP-treated hens was not significant, owing to large interbird variations. Since TOTP-treated hens showed greater disturbances in gait following moderate exercise, the fatigue of posttetanic potentiation with periodic neuronal stimulation was measured.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Glutathione depletion and resynthesis in laboratory animals.

The availability of tissue glutathione (GSH) appears to depend upon a balance between tissue concentrations, the rate of reactive metabolite formation and the re-synthesis of GSH. To test this hypothesis, diethyl maleate (DEM, 5.8 mmol/kg bw) was administered intraperitoneally to male and female mice, hamsters, rats and guinea pigs. The regeneration of hepatic and renal GSH was examined at 0.5, 1, 2, 4, 8 and 24 hr post-treatment. DEM caused a rapid and marked depletion of tissue GSH but re-synthesis began to occur by 4 hr post-treatment in all species with the exception of the guinea pig. By 24 hr after treatment, the mouse, hamster and rat had tissue levels of GSH in excess of usual values but, in the guinea pig, recovery of hepatic GSH was still significantly reduced. Considering the reported species differences in S-alkenetransferases which detoxify DEM, the present results revealed that the conjugation of DEM proceeded rapidly in all four species but that the toxicity elicited in the guinea pig may have arisen from the unavailability of GSH during the slow re-synthesis stage following maximal depletion of this agent.

Animals↗
PubMed1983

Transplacental and milk transfer of polybrominated biphenyls to perinatal guinea pigs from treated dams.

Timed-pregnant albino Hartley strain guinea pigs of approximately 65 days gestation or lactating animals within 6-12 h of parturition received a single oral dose of Firemaster FF-1 (50 mg/kg body wt). The pregnant animals and their fetuses were killed 2 days later at term while the lactating animals and their pups were killed at intervals of 2, 4, 7, 14, 28, 42, and 60 days. Tissues (liver, kidney, lung, perirenal fat) were removed for the analysis of the 2,4,5,2',4',5'-hexabromobiphenyl (HBB) isomer content by gas-liquid chromatography following extraction. Microsomes were prepared from samples of fresh liver for the analysis of hepatic mono-oxygenase (p-nitroanisole O-demethylase, aniline hydroxylase) and UDP-glucuronosyl-transferase activities. Transplacentally-acquired residues of the order of 45 micrograms HBB/g were found in both maternal and fetal adipose tissue and in fetal liver. HBB residues in maternal kidney, lung and liver were of the order of 4-7 micrograms/g while, in the fetuses and pups, levels in the kidney and lung were of the order of 1-2 micrograms/g. Levels of HBB in breast milk 2 days after treatment averaged 22.4 +/- 7.8 micrograms/g (mean +/- S.D.). A marked induction of hepatic microsomal mono-oxygenases was observed in guinea pig pups concomitant with elevated hepatic levels of HBB (9-19 micrograms/g) which decreased with time as the agent was redistributed into adipose tissue. By 7 days of age the pups had been weaned and by 14 days of age the enzymatic activities were comparable to those measured in control pups. HBB levels in the pup kidney, lung and adipose tissue reflected redistribution or sequestration in the body fat. The biological half-life of HBB in tissues of both dams and pups appeared to be approximately 22 days.

Animals↗
PubMed1982

Disposition of maternally-administered methadone and its effects on hepatic drug-metabolizing functions in perinatal guinea pigs.

Racemic methadone HCl(25 mg/kg given every 12 hr for 2 consecutive days) was administered orally to pregnant (60-65 days of gestation) or nursing (0-8 days post-partum) albino guinea pigs. The dams, fetuses and pups were killed 12 hr after the last dose for the analysis of maternal and perinatal plasma, brain, hepatic and renal methadone residues by GLC and the in vitro measurement of maternal and perinatal microsomal mono-oxygenase [p-nitroanisole O-demethylase (OD) and aniline hydroxylase (AH)] and glucuronosyltransferase (GT) activities. Methadone was acquired by the perinatal guinea pig both transplacentally and via the milk, more agent being obtained by the former route. Fetal plasma levels of methadone were consistently lower than those detected in the mother due, largely, to differential plasma protein binding. The perinatal pattern of tissue distribution of methadone was markedly different from that observed in the dam, exceedingly high levels being found in fetal brain and kidney. Maternally-administered methadone did not affect the ontogenesis of perinatal OD, AH and GT but it did reduce significantly the levels of hepatic GT activity in the pups and in the dams.

Aging↗
PubMed1982

Aerial spraying of fenitrothion in forest programs: some problems and some solutions.

Annually, large tracts of forest in eastern Canada are sprayed aerially with insecticides (fenitrothion, aminocarb) in attempts to control an epidemic infestation by an indigenous forest pest, the spruce budworm (Choristoneura fumiferana, Clemens). The massive size of the spraying programs, the anecdotal reports of human exposure, and the potential for hazard to human health have led one province. New Brunswick, to initiate and fund specific environmental and laboratory studies which will provide adequate data upon which the government can base realistic legislation to protect both the forests and the population. These studies have included some unique field analyses of aerial spray drift conducted by a research group from the National Research Council; comparative subchronic studies in rats of fenitrothion and a new formulation; a nose-only inhalation study of this formulation in rats; field testing of the formulation for drift characteristics. Ongoing research involves the subchronic testing of the emulsifying agents being used routinely in the new formulation and studies of a low-drift additive which will stabilize the particle size of the spray. On the basis of the results to date, the government has been able to modify spraying techniques and to establish realistic buffer zones around human habitation.

Aerosols↗
PubMed1981

The induction of rat lung aryl hydrocarbon hydroxylase by diluted smoke from commercial cigarettes.

Induction of pulmonary aryl hydrocarbon hydroxylase (AHH) by cigarette smoke in small rodents is well established. However, studies on dose-response relationships particularly at the lower ends of such relationships are few indeed. Availability of the British-American Tobacco Co. (B.-A.T.)-Mason inhalation system, in which precisely-calibrated dilutions of cigarette smoke can be released into an inhalation chamber, enables excellent dose-response relationships to be established. Using this inhalation system and cigarettes delivering tar (total particulate matter, water and nicotine free) equal to 1, 4 and 20 mg/cigarette, it has been shown that induction of AHH in male Sprague-Dawley rat lung is an extremely sensitive system to inhaled cigarette smoke. AHH induction was observed at a 200-s exposure to 40 puffs of a 1 : 5 dilution of smoke from an ultramild cigarette delivering 1 mg tar. At this low concentration, it is not even possible to accurately weight the TPM from diluted smoke in the exposure chamber. This extremely sensitive rat pulmonary enzyme system may prove valuable in the biological testing of modern low tar cigarettes.

Animals↗
PubMed1981

Methadone hydrochloride: acute administration, disposition and effects on hepatic function in guinea pigs.

d,1-Methadone hydrochloride was administered orally to adult female albino guinea pigs at a dose of 25 mg/kg body weight every 12 h for 10 consecutive days. Twelve hours after a dose, subgroups of animals were sacrificed at 2, 5 and 10 days for tissue (blood plasma, brain, liver and kidney) methadone residue analysis and the in vitro measurement of hepatic microsomal p-nitroanisole O-demethylase (OD), aniline hydroxylase (AH) and glucuronosyltransferase (GT) activities. No overt toxicity was observed during treatment other than a decrease in body weight. Withdrawal signs were absent during the 14-day post-treatment regression period. Tissue methadone levels were constant except for a decreased concentration in the liver at 5 and 10 days. No effect on hepatic OD and AH was observed during treatment but a significant decrease in GT activity was measured which returned to normal values 14 days after terminating treatment.

Animals↗