Showing papers in "Veterinary and Human Toxicology in 1988"

Pharmacology and toxicology of doxycycline.

Abstract: Doxycycline, a structural isomer of tetracycline, has been used in human medicine since 1966. The molecule, obtained semi-synthetically from oxytetracycline or methacycline, is highly lipophilic permitting excellent penetration into tissues. In vitro antimicrobial activity of doxycycline is superior to that of the older tetracyclines (chlortetracycline, oxytetracycline, tetracycline). In laboratory animals, the protective dose for 50% of the subjects (PD50) demonstrates a better in vivo activity than that of all other members of the tetracycline family. Clinical use in human medicine has confirmed the efficacy of doxycycline for a variety of infectious conditions. High lipophilicity results in a large volume of distribution, substantial binding to plasma proteins, and reabsorption in the renal tubules and gastrointestinal tract, thereby conferring a long elimination half-life to the drug. Excellent absorption after oral administration allows small oral doses and minimizes the known side effects of tetracyclines on the gastrointestinal tract--irritation and suprainfection. The contrast to the other tetracyclines, doxycycline does not accumulate in renal failure due to a compensatory gastrointestinal secretion. The pharmacology, toxicology and therapeutics of doxycycline in laboratory animals and man indicate that this drug may be a valuable antimicrobial for use in veterinary medicine.

Fructooligosaccharides: a review.

Abstract: Fructooligosaccharides are naturally occurring compounds that have been reported in a variety of plants. Neosugar is a fructooligosaccharide mixture of 1F-(1-beta-fructofuranosyl)-sucrose polymers which is produced on a commercial scale from sucrose using a fungal fructosyltransferase. The resulting product is 0.4 to 0.6 times as sweet as sugar and is resistant to digestion by mammalian alpha-amylase, sucrase and maltase. Although Neosugar is non-digestible in humans, it is selectively utilized by bifidobacteria. Neosugar has been examined extensively in human and animal studies which indicate a lack of toxicity, carcinogenicity and genotoxic effects. Neosugar is used as a feed additive for poultry and swine in Japan and has been approved in foods as a raw material. Additional studies in progress in the US suggest that it could provide an economic alternative as an additive to poultry and swine feed.

Paraquat intoxication during pregnancy: a report of 9 cases.

Abstract: The details of nine patients who deliberately ingested paraquat (24% solution) while pregnant are presented. Two patients refused treatment. Paraquat levels in maternal, fetal and cord blood in 1 case shows that paraquat crosses the placenta and is concentrated to levels 4-6 times greater than the maternal blood. Amnioscopy in another case showed paraquat levels in amniotic fluid nearly twice that of maternal blood. All fetuses died, whether or not emergency cesarean operation was performed. The condition of the fetus worsened at delivery, or in utero if the gestational age was greater than 30 weeks. One of the 2 survivors has had a normal pregnancy since, with no evidence of teratogenicity from the earlier paraquat intoxication. This patient has shown a gradual return to normal spirometry values from the marked reduction that occurred at the time of paraquat intoxication.

Acute zinc intoxication: comparison of the antidotal efficacy of several chelating agents.

Abstract: Four zinc compounds (acetate, nitrate, chloride and sulfate) were administered po or ip to rats and mice. The LD50 values were determined. Animals were observed for 14 days. The majority of deaths occurred during the first 48 hr. The clinical and physical signs appearing after intoxication included miosis, conjunctivitis, decreased food and water consumption and hemorrhages and hematomas in the tail. These changes decreased with time which would suggest a quick elimination of zinc. To determine the effect of 6 chelating agents on the toxicity of zinc, various doses of zinc acetate (66-330 mg/kg) were given ip to male mice followed by the injection of one of the chelators. DTPA, D-PA, CDTA and EDTA were the most effective. CDTA and DTPA were also the most effective in increasing the urinary excretion of zinc. DTPA appears to be the most effective agent of those tested in the prevention of acute zinc intoxication. However, CDTA may be considered as a possible alternative.

Effect of repeated dermal application of endosulfan to rats.

Abstract: Dermal application of endosulfan to male (18.75, 37.50 and 62.50 mg/kg/day) and female (9.83, 19.66 and 32.0 mg/kg/d) rats for 30 days produced hyperexcitability, tremor, dyspnea and salivation. There were no deaths. The signs of toxicity subsided after a week. Endosulfan produced no significant changes in the organ:body weight ratio. No significant changes were seen in the histological and hematological indices. However, a significant decrease in liver GOT and GPT and serum GPT activities and a significant rise in serum alkaline phosphatase and total protein were recorded in the endosulfan-treated animals. There were no changes in LDH. Residue analysis revealed higher levels of total endosulfan in fatty tissues of rats receiving the highest dose of endosulfan.

Sulfadimethoxine pharmacokinetics and metabolism in the channel catfish (Ictalurus punctatus).

Abstract: The pharmacokinetics of sulfadimethoxine (SDM) blood clearance, gastrointestinal absorption and tissue distribution and elimination were determined in channel catfish (Ictalurus punctatus) after intravenous and oral dosing using radiolabelled SDM. Blood clearance of SDM in catfish was rapid compared to mammals when the drug was given iv. Results from in vitro equilibrium dialysis studies suggest that this is due to a lower binding of SDM to plasma proteins in fish (18.4%) compared to mammalian species (60-88%). Results from oral dose studies indicated that SDM is readily absorbed from the gastrointestinal tract in channel catfish and distributes rapidly to body tissues, primarily the muscle. With time, concentrations of SDM in muscle decrease and the drug accumulates in the bile, primarily as the N-acetyl-metabolite.

Toxicology of thiram (tetramethylthiuram disulfide): a review.

Abstract: The acute oral toxicity (LD50) o: ~=~~a= for mammals ranges frem 230 to 2,8 ° =5 ~5 (Table 1). AnimaIs killed by sing:e ~a: doses of thiram showed hyperemia, = ca: ulceration oi the gastro-intesLi a: ~ra~-, focal necrosis oi liver and rena~ -'b~:es and patchy demye1ination in Lhe cere~e::~ and medulla (9). Symptoms ai ac ~e ~L~ra= poisoning in humans include nausea, ,a=~~~=g, diarrhea, headache, lethargy, d~zz~=ess, ataxia, coniusion, drowsiness, f acc~~ paralysis and death. li deaLh ooes cooccur, recavery tends to be co~p:eLe w~~~~= 1 or 2 w~eks.

Delayed manifestation of Senecio-induced pyrrolizidine alkaloidosis in cattle: case reports.

Abstract: Selected case reports from closely controlled experimental feedings of Senecio jacobaea (tansy ragwort), S longilobus (threadleaf groundsel) and S riddellii (Riddell's groundsel) to cattle are presented to show that all 3 of these pyrrolizidine alkaloid-containing plants may not necessarily induce proximate toxicity, but may cause typical signs and death many months after the plants are ingested. Results of the experimental intoxications indicate that if the daily dosage is of sufficient size to insult hepatocytes, a chronic lethal dose of plant may be eaten in only a few days. Early signs of intoxication may be absent, or mild and transitory, and serum enzyme changes that reflect liver injury may not always be detectable. Latent pyrrolizidine alkaloidosis signs can develop many months after the plants are eaten, and death imminent soon thereafter. The prepatent period and eventual time of death appears to be dependent on the time-dose relationship that determines the rate of progressive hepatocellular injury.

Formulas predicting carboxyhemoglobin resulting from carbon monoxide exposure.

Abstract: A microcomputer program in BASIC for predicting the percent carboxyhemoglobin of blood in men exposed to carbon monoxide is designed. Formulas used in this program are derived from the data reported by Forbes, Sargent and Roughton. A general formula previously published by the author expresses the mathematical relationship among the intensity of a stressor, the time of exposure, and the occurrence of a biological response. This formula is implemented in this study, using carbon monoxide as the specific stressor. Analysis of the reported and the computer-assisted predicted data has shown that the program for the constructed formulas is fairly accurate and reliable in expressing carboxyhemoglobin as a function of the air CO concentration and the time of exposure. The predictive formulas can determine the relationship among the carbon monoxide concentration in air, the time of exposure, and the percent carboxyhemoglobin level of blood, and may be of value in industry, in environmental protection and in medicine.

Individual animal susceptibility and its relationship to induced adaptation or tolerance in sheep to Galega officinalis L.

Abstract: Oral administration of Galega officinalis L to sheep demonstrated a marked variation in individual animal susceptibility to the toxic effects of the plant. As little as 5 g/kg of dried ground plant induced moderate tracheal frothing in 1 ewe while nearly 5 times that amount failed to elicit any recognizable toxic effects such as frothing, pulmonary edema or hydrothorax in others. Ten g/kg induced severe effects in 3 ewes. Ewes administered levels of plant between 5 and 24 g/kg had toxic effects whose severity was often unrelated to level administered. There was no apparent difference in average severity of clinical signs of toxicity nor pathologic lesions to challenge doses of 24 g/kg of the plant between groups of ewes with an immediate previous history of increasing doses of the plant and others with no history of ingesting the plant. Previously reported apparent induced adaptation or tolerance to G officinalis L in some animals is more likely to have been a result of the extreme variation in individual animals susceptibility.

Indicators of lead, zinc and cadmium exposure in cattle. I. Results in a polluted area.

Abstract: Dairy cattle on a farm located in the vicinity of a lead and zinc-ore processing factory were studied over 21 mo and compared with cattle on a control farm. Mean daily intakes of lead from the diet were 4.3 mg/kg body weight, with great variations; mean daily zinc intakes were 5.6 mg/kg body weight; and mean daily cadmium intakes were 0.064 mg/kg body weight. The 3 major indicators of contamination were blood lead concentrations, with mean values of 50 micrograms/100 ml of blood, zinc protoporphyrin with mean values of 165 micrograms/100 ml blood, and lead concentrations in hair which averaged 10 micrograms/g. Blood zinc concentrations and zinc concentrations were not significantly increased. One cow developed fatal post-partum paralysis. Liver, kidney and bone lead concentrations and kidney cadmium concentrations were good "post-mortem" indicators of exposure.

Myonecrosis in carbon monoxide poisoning

Abstract: Myonecrosis is an unusual sequelae to carbon monoxide poisoning with only 16 cases having been reported in the English-language literature. At the University of Illinois Hospital, we encountered a 25-year-old fire academy student who presented to our Emergency Department with a carboxyhemoglobin level of 16% following a training exercise in a smoke-filled room. The patient was not wearing a self-contained breathing apparatus and his duration of exposure was 7-8 min, by which time he had blacked out for about 1 min. Upon arrival, the patient was lethargic, with a moderate inhalation burn. The patient was treated with hyperbaric oxygen at 2 1/2 ATA. Following 90 min of hyperbaric oxygen, slight flexor compartment weakness, along with tenderness of the proximal lower extremities was noted. CPK was elevated to 65,998 (100% mm) with urine dipstick being positive for blood and only occasional rbc's seen in the urine sediment. The patient did well with forced diuresis and alkalinization of the urine. No oliguria was noted and the CPK fell to 893 five days later. This is the only case in the English-language literature who developed myonecrosis from carbon monoxide, despite hyperbaric oxygen treatment. We believe that this case demonstrates that hyperbaric oxygen cannot prevent the development of myonecrosis induced by carbon monoxide.

Kerosene aspiration: immediate and early pulmonary and cardiovascular effects.

Abstract: Hydrocarbon aspiration is responsible for substantial morbidity and mortality in both children and domestic animals. To better understand the pathogenesis of hydrocarbon poisoning, we evaluated the effects of aspiration of 0.5 ml/kg of kerosene on various pulmonary and cardiovascular variables over a 4-hr period in a canine model. Heart rate and blood pressure decreased immediately after kerosene aspiration but returned to control values within 60 min. Respiratory rate and intrapulmonary shunting were increased and PaO2 was decreased for up to 4 hr after kerosene aspiration. PaCO2 increased and pH decreased immediately after aspiration but returned to baseline within 45 and 90 min, respectively. Intrapleural pressure became more negative after kerosene was aspirated, which suggests that total lung compliance was diminished. Kerosene aspiration resulted in severe and persistent intrapulmonary physiologic shunting, hypoxemia, bradycardia, and hypotension.

The toxicity of Indian Calotropis procera RBr latex in the black rat, Rattus rattus Linn.

Abstract: Toxicity studies with latex of Calotropis procera RBr were conducted in the black rat, Rattus rattus. The latex was fed through bait prepared from wheat flour, ground nut oil and sugar at concentrations of 5, 7.5 or 10% (W/W). The bait was fed up to mortality and for a maximum of 10 days. The signs produced were passivity, sluggishness, sedation, dyspnea, weakness, reduction in weight, anorexia, diarhhea, hematuria, bleeding from nose, eyes and anus, eye lens opacity, mild tetanic convulsions, collapse and death. The observed mortalities were 56.25, 68.75 and 87.5% with the respective doses. Histopathological studies showed: cloudy swelling of hepatocytes, inflammatory changes, Kupffer cell hyperlasia, cytoplasmic granulation, hepatocytolysis, compactness of lobular architecture, and occasional hemorrhage in the liver; cloudy swelling of convoluted tubular epithelium, inflammatory changes and hemorrhage in the kidney; erosion, increased mucus secretion, congestion and infiltration of lymphocytes in portions of the alimentary canal.

Signal grass (Brachiaria decumbens) toxicity in sheep: changes in motility and pH of reticulo-rumen.

Abstract: In addition to generalized icterus, enlargement of the liver and severe photosensitization, signal grass (Brachiaria decumbens) toxicity also caused ruminal stasis and a decreased rumen pH in sheep. Ruminal stasis, which occurred within 3 weeks of grazing on this grass, may be the effect of the toxin produced in the rumen rather than a sequele of a decreased rumen pH. Animals were anorexic and the volume of their rumen content was very much reduced.

Comparative drug metabolism and disposition in minor species.

Abstract: The disposition of fenbendazole (FBZ) was studied in vivo in cattle (steers), goats, chickens, ducks, turkeys and rabbits, and in vitro in hepatic enzyme preparations from cattle, sheep, goats, rabbits, rats, chickens, ducks, turkeys and catfish. The major excretory metabolite when FBZ was administered either iv or po (5 mg/kg) was p-hydroxyfenbendazole (FBZ-OH). The sulfoxide (FBZ-SO) and sulfone (FBZ-SO2) appeared in plasma but were recovered in only trace amounts in urine or feces, and the amine (FBZ-NH2) was a minor metabolite appearing only occasionally in plasma. The greatest species differences were seen among the avian species, and differences in metabolite excretion correlated well with the ability of the species to metabolize the drug (especially to FBZ-OH) in vitro. Other in vitro studies measured the rate of oxidative, hydrolytic, and conjugative (glucuronide, acetate, sulfate) pathways in liver preparations.

Microsomal enzyme induction by permethrin in rats.

Abstract: The synthetic pyrethroid, permethrin, was evaluated for its ability to alter hepatic microsomal drug-metabolizing function. The influence of permethrin (25:75 cis-trans) on plasma antipyrine kinetics and gamma-glutamyl transpeptidase (gamma-GTP) activity were studied in rats. After 3 days of administration of 90 mg permethrin/kg/day, there was no significant change in the antipyrine half-life and the area under the curve, while the apparent volume of distribution and clearance were significantly increased. Treatment with 190 mg permethrin/kg/day for 3 days decreased antipyrine half-life and the area under the curve, and increased the apparent volume of distribution and the clearance significantly. The gamma-GTP activity was significantly increased within 21 days and 14 days after the start of permethrin administration, at doses of 90 and 190 mg permethrin/kg/day, respectively. The antipyrine kinetics results indicate that permethrin is capable of producing a dose-dependent marked enzyme-inducing effect.

Selected incidents of illnesses and injuries related to exposure to pesticides reported by physicians in California in 1986.

Abstract: California collects data on most occupational and many non-occupational illnesses and injuries related to pesticide exposure. Most of the occupational incidents are investigated by local agencies. A thorough investigation is conducted on all pesticide-related cases that meet "priority" guidelines: death; hospitalization of 1 or more persons for more than 24 hours with treatment; or 5 or more people with symptoms seeking medical care as a result of the same incident. This report summarizes the priority cases determined to be related to pesticide exposure during 1986. Of the 67 described incidents, involving 583 people ill, 26 (38%) were related to exposure to pesticides applied indoors (residences, offices), either by commercial pest control companies, employees or homeowners. Nearly 200 people (33%) became ill and more than 200 people were evacuated as a result of these types of applications. Most of these incidents were a result of careless application techniques and not following label instructions. Four other incidents, with 33 people ill, were the result of spills in retail stores. In all 4 cases, store employees tried to clean the spill without wearing protective clothing. Two other cases involved exposure via a pesticide being put in a food container. Nineteen of these type of incidents involved a pesticide product containing an organophosphate; most often chlorpyrifos (8 incidents), diazinon (3 incidents), and malathion (5 incidents). There were also 10 cases that resulted from suicide; eight different pesticides were involved. Five incidents involving agricultural workers, as well as 4 incidents involving non-agricultural workers, were primarily the result of allowing pesticides to drift from the target field.(ABSTRACT TRUNCATED AT 250 WORDS) Language: en

Chlorine poisoning at the swimming pool revisited: anatomy of two minidisasters.

Abstract: A case of acute chlorine gas exposure in a swimming pool attendant was previously reported (Clin Tox 13:377-381, 1978) In April 1986, approximately 30 people, including a swimming coach, lifeguards, and competitive swimmers ranging in age from 5 to 12 years old, were exposed to heavy concentrations of chlorine gas at a large indoor swimming pool The coach, one lifeguard, and 18 of the children were hospitalized In June 1988, a similar exposure occurred at the same swimming pool, and 11 persons were affected Information from these 2 incidents illustrates 4 important factors in disaster prevention and management: proper training of equipment operators, effectiveness of triage, information flow to relatives of the afflicted, and requisite posthospitalization followup to detect possible long-term adverse effects

Indicators of lead, zinc and cadmium exposure in cattle: II. Controlled feeding and recovery.

Abstract: Two pre-exposed and 2 normal heifers were fed lead (Pb), zinc (Zn), and cadmium (Cd) polluted hay (500 g/100 kg body weight) over a 17-week period. They were then examined over a 10-month period (42 or 38 weeks) to study the decay of the indicators of exposure. The elimination pattern of blood Pb and Zn protoporphyrin concentrations displayed a very slow decay. A bi-exponential equation, with the half-times of the fast component set at approximately 1 week, and the half-times of the slow component set from 3 mo to 2 years, was fitted to blood Pb levels. In man, the half-life of the slow component is still longer (2 to 15 years). This slow elimination rate represents release of Pb from skeleton, which in bovines, may accumulate up to 100 ppm Pb/dry or more. Lead concentrations in the hair were not proportionate to the areas under the curves of blood Pb levels; there was the same lack of correlation concerning skeleton and viscerae Pb levels. The withdrawal of contaminated hay from the diet resulted in a significant increase in blood copper. This is in accordance with the depressive effect of Pb and Zn on the bioavailability of this metal.

Disseminated intravascular coagulation in a case of fatal lindane poisoning.

Abstract: After an accidental or intentional ingestion of lindane, clinical manifestations of poisoning may include rapid onset of nausea and vomiting, coma, seizures, respiratory failure, and death. While rhabdomyolysis, secondary renal failure, and aplastic anemia have also been reported, coagulopathies have not been observed following poisoning with this pesticide. In this case report we describe a 43-year-old female who intentionally ingested 8 oz of a 20% lindane solution. Her serum lindane concentration reached 1.3 mcg/ml and her clinical manifestations included seizures, coma, rhabdomyolysis, secondary renal failure, and disseminated intravascular coagulation. The coagulopathy presented early in her clinical course and resolved when serum lindane levels fell. The patient died 11 days after the ingestion.

Additional deaths associated with the intentional inhalation of typewriter correction fluid.

Abstract: The previously published literature contains at least 27 deaths associated with the intentional concentration and inhalation of typewriter correction fluid (TCF). The solvent systems of TCF products include volatile halogenated hydrocarbons such as 1,1,1-trichloroethane and trichloroethylene. This report describes 3 additional deaths resulting from TCF abuse, including 1 case in which the addition of mustard oil to the product failed to deter abuse.

A review of the pharmacokinetics and metabolism of sulfadimethoxine in the rainbow trout (Salmo gairdneri).

Abstract: The pharmacokinetics and metabolism of sulfadimethoxine (SDM) was examined in the rainbow trout. Results from pharmacokinetic studies indicate a lengthening of the SDM half-life when administration was shifted from single to a multiple dose regime. In contrast to mammals and similar to the catfish a low magnitude nonspecific plasma protein binding was evident with SDM. Volume of distribution data indicates that SDM is distributed in plasma, extracellular and to a limited degree, intracellular fluid spaces. This distribution was greater than that demonstrated for mammals; however, lower than for the lobster or catfish. Absorption of SDM from the trout gastrointestinal tract varied with chemical form and dosage. Lower relative bioavailability values were evident with crystalline SDM and with high doses of the sodium salt. SDM accumulated to the highest levels in the bile followed by the intestine, liver, blood, skin, kidney, spleen, gill, muscle and fat respectively. Biliary SDM was composed of parent, N-acetylated SDM, an unknown polar metabolite, and what appears to be a sulfate conjugate.

Experimental Chrozophora plicata poisoning in goats and sheep.

Abstract: The clinical, biochemical and pathological effects of the fresh shoots of Chrozophora plicata on Nubian goats and Desert sheep were investigated The animals were given single or repeated daily doses of 10, 5, 1 and 05 g/kg of chrozophora shoots by stomach tube and died at various times post dosing The main signs of Chrozophora poisoning in both species of ruminants were salivation, dyspnea, bloat, inappetence, dullness, diarrhea, paresis of the hind limbs, recumbency and lateral deviation of the head and neck The main lesions were hemorrhage in the lungs, heart and kidneys, pulmonary cyanosis and edema, hepatic fatty change and depletion of glycogen, catarrhal enteritis, ascites, hydropericardium and serous atrophy of the cardiac fat and renal pelvis An increase in the concentration of urea, ammonia and bilirubin and in the activity of GOT and a decrease in total protein were detected in the serum Hematological changes indicated the development of anemia

An epidemiological investigation associating aflatoxin M1 with milk production in dairy cattle.

Abstract: An attempt was made to utilize the analysis for aflatoxin M2 in milk, instead of aflatoxin B1 in feed for a pilot epidemiological study addressing the association of M1 levels and various production parameters. Four dairy farms, representing above average to below average management practices, were identified with 10 animals being randomly selected from each farm for this study. Milk samples and production data were evaluated from these animals in order to gain insight into the possible effects of low level mycotoxin ingestion on production and to test whether or not this approach offered potential for future epidemiological studies. Feed samples were basically negative for the presence of aflatoxin B1, yet milk analysis revealed the presence of M1 in a large percentage of the animals. Further, the M1 levels appeared to be associated with a decrease in daily milk production. This study indicates that employing M1 analysis in milk for epidemiological investigations of low level mycotoxin ingestion effects, instead of B1 feed analysis, is feasible and offers a potential for more definitive studies in this area.

Systemic manifestations of erucism: a case report.

Abstract: Larvae of the caterpillar Thaumetopoea wilkinsoni are widely distributed in pine groves throughout Israel. Erucism is defined as urtication by Lepidoptera larvae. Both irritating effects on contact with skin and eyes and toxic effects on ingestion have been described after exposure to several species of Lepidoptera. We report the case of a 4-year-old child who vomited repeatedly and developed symmetrical swelling of both hands after touching a larva of Thaumetopoea wilkinsoni.