ABSTRACT
Synthetic delta 9-tetrahydrocannabinol (THC) was dissolved in undiluted propylene glycol and administered in daily subcutaneous doses of 15.0, 30.0 or 60.0 mg/kg to pregnant New Zealand white rabbits on days 7--19 of gestation. Maternal food consumption and weight gain were markedly reduced at all dose levels. Embryotoxicity and embryocidal effects were observed in the form of reduced litter weight and number of viable fetuses, respectively, in offspring from pregnant mothers treated with THC. However, on the basis of extensive external, visceral and skeletal examination of all fetuses it may be concluded that THC is not teratogenic in the New Zealand white strain rabbit following subcutaneous administration of doses as high as 60.0 mg/kg/day during the critical period of organogenesis (days 7--19 of gestation). On the other hand, an oral dose of thalidomide (200.0 mg/kg/day), the positive control used in this study, was both embryocidal and teratogenic.
Subject(s)
Abnormalities, Drug-Induced , Dronabinol/toxicity , Animals , Body Weight/drug effects , Dronabinol/administration & dosage , Eating/drug effects , Female , Fetal Viability/drug effects , Gestational Age , Pregnancy , Rabbits , ThalidomideSubject(s)
Butanols/toxicity , Animals , Blood Cell Count , Body Weight/drug effects , Butanols/blood , Butanols/urine , Dogs , Female , Male , Organ Size/drug effects , Rats , Sex Factors , Species Specificity , Time FactorsABSTRACT
The acute and subacute toxicity of 4-(p-chlorophenylthio) butanol (W-2719), on anti-allergy agent, was investigated in mice, rats and dogs. Acute LD50 values in the mouse (1145.0 mg/kg p.o.) and rat (greater than 1400.0 mg/kg p.o.) and maximum tolerated dose in the dog (420.0 mg/kg p.o.) were very high, indicative of a high degree of safety following a single oral dose. The subacute toxicity studies were conducted by repeated daily oral administration of the compound for 30 days. In the rat, W-2719 did not produce any significant toxicity up to a dose level of 100.0 mg/kg/day, when administered as a drug-diet admixture. A higher dose, i.e., 200.0 mg/kg/day, produced marked reductions in body weight gain, food consumption, RBC and WBC (females especially), and other hematological parameters. In the purebred beagle dog, W-2719 did not produce any significant toxicity up to a dose level of 100.0 mg/kg/day, the highest dose level tested in this species.
Subject(s)
Butanols/toxicity , Histamine Antagonists/toxicity , Animals , Chlorobenzenes/toxicity , Dogs , Female , Lethal Dose 50 , Male , Mice , Organ Size/drug effects , Rats , Sex Factors , Species Specificity , Time FactorsSubject(s)
Blood Proteins/analysis , Lupus Erythematosus, Discoid/blood , Psoriasis/blood , Vitiligo/blood , Adolescent , Adult , Blood Protein Electrophoresis , Child , Female , Humans , Male , Middle AgedABSTRACT
The acute and subactue toxicity of 2,3-dihydro-9H-isoxazolo[3,2-b]quinazolin-9-one (W-2429), a non-narcotic analgesic agent, was investigated in mice, rats and dogs. The subacute toxicity study was conducted by repeated oral administration of the compound for 30 days. Treatment with W-2429 was well tolerated by rats as well as dogs. In the dog, the only signs of toxicity observed were decreased appetite and salivation at 100 mg/kg/day. No other significant evidence of physical, chemical, gross or histopathologic change was observed.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/toxicity , Isoxazoles/toxicity , Oxazoles/toxicity , Quinazolines/toxicity , Animals , Blood Cell Count , Blood Chemical Analysis , Body Weight/drug effects , Dogs , Female , Lethal Dose 50 , Male , Mice , Organ Size/drug effects , Rats , Spermatogenesis/drug effects , Time FactorsABSTRACT
Delta9- Tetrahydrocannabinol (THC) was administered subcutaneously to female New Zealand white strain rabbits for 13 days. The animals were randomly divided into six groups of five animals each of which consisted of untreated controls, vehicle (undiluted propylene glycol)-treated, and THC treatment at dose levels of 100, 30, 10, and 3 mg/kg/day. All animals survived for the duration of the study. The THC-treated rabbits did not gain significant body weight which seems to be due to a decreased food consumption. There were some variations in various hematologic values, but they all were within the normal range for our laboratory. Blood chemistry evaluations showed decreased serum levels of potassium, glucose, blood urea nitrogen, alkaline phosphatase, and albumin/globulin (A/G) ratio and an increase in cholesterol levels of all treated animals. A significant increase in billirubin values was noted in the animsls of the 3- and 10-mg/kg groups. The injection site in the skin of the THC-treated rabbits showed signs of local irritation (erythema and subcutaneous abscesses). There was a reduction in absolute and percent of body weight of the liver and absolute weight of the lungs of the treated animals. However, no histopathologic alterations were observed. It may be concluded that THC treatment subcutaneously for 13 days in rabbits up to a dose level of 100 mg/kg/day did not produce any significant toxicity, except anorexia and some local dermal irritation.
Subject(s)
Cannabis/toxicity , Dronabinol/toxicity , Animals , Blood Chemical Analysis , Body Weight/drug effects , Feeding Behavior/drug effects , Female , Organ Size/drug effects , Rabbits , Time FactorsABSTRACT
Delta-9-Tetrahydrocannabinol (THC) was dissolved in propylene glycol and 25, 50, or 100 mg/kg administereed dialy sc to pregnant Charles River Sprague-Dawley rats on days 6-15 of gestation (presence of sperm considered day 1). Maternal weight gain was depressed, but a significant decrease in fetal weight occurred only in the 50 mg/kg group. No malformations were noted, only some abnormalities consisting of several instances of rudimentary 14th rib and soft or spongy spinal cords.
