RESUMO
The acute oral toxicity data for 10 compounds, generated by using two alternative methods in rats, the up-and-down method and the fixed-dose procedure, were compared with those obtained from the classical LD50 test. In this evaluation, both alternative methods offered a reduction in animal use, while providing adequate information to rank the compounds according to the EEC classification for acute oral toxicity. In addition to the ranking, these alternative methods also provided useful information on signs of toxicity and gross autopsy findings, although the results varied depending on the method used. Of the three methods, the up-and-down method required the fewest animals. Although the up-and-down method used only females, the LD50 values obtained were in good agreement with those obtained by the classical method, which used both sexes. It is concluded that the up-and-down method and the fixed-dose procedure are acceptable alternative methods to the classical LD50 test, and the choice of method depends on the type of toxicity information required.
Assuntos
Toxicologia/métodos , Administração Oral , Animais , Relação Dose-Resposta a Droga , Feminino , Dose Letal Mediana , Masculino , Ratos , Ratos Endogâmicos , Fatores de TempoRESUMO
Some chemical which are injurious to the eye may also cause anesthesia. If the eye were unknowingly anesthetized, exposure to an irritant could go undected and cause injury. Techniques for determining whether the eye was anesthetized have been generally unreliable. Usually the technique consists of challenging the cornea with a probe and testing for a blink response. In a new method described herein, an indwelling subpalpebral lavage apparatus was surgically implanted in the dog. Through this apparatus, a test material was instilled into the eye without the animal's anticipation. Responses caused by the materials were monitored by electroencephalography. The normal response to an irritting material was increased frequency and decreased amplitude of the electroencephalogram tracing or a deflection of thepolygraph needle (blink response), or both. The method was evaluated with known eye anesthetic agents and appeared to be a useful way of detecting eye anesthesia.
Assuntos
Anestesia Local/veterinária , Cães/fisiologia , Olho/efeitos dos fármacos , Anestesia Local/métodos , Animais , Eletroencefalografia , Modelos Biológicos , Fenômenos Fisiológicos Oculares , Propoxicaína , Cloreto de Sódio/farmacologia , Tetracaína , Irrigação Terapêutica/instrumentaçãoRESUMO
Animal models historically used to assess the acute gastric irritation potential of accidental ingestion of consumer products include the dog, pig, rabbit, and cat. In looking at alternative methods that are of shorter duration and more cost-effective, the rat is being evaluated as a potential model. Acute gastric irritation is known to increase as the reserve alkalinity of the formulation increases. In initial experiments to assess the rat as a potential model, animals were dosed via oral gavage with 1 of 4 formulations ranging in reserve alkalinity from 4.0 to 10.8. Necropsies were performed at 15 and 60 min after dosing. Macroscopic and microscopic evaluations of the stomach revealed morphological differences in the various treatment groups that distinguish granular formulations having either a low (R.A. = 4.0), moderate (R.A. = 7.1), or higher (R.A. = 10.8) reserve alkalinity. Additionally, it was observed that the acute gastric changes in rats dosed with a liquid formulation having a low (R.A. = 4.2) reserve alkalinity were similar to those in rats dosed with a granular formulation having a moderate reserve alkalinity (R.A. = 7.1). This suggests that other factors such as types of ingredients, pH, and physical form influence the extent of acute gastric irritation and demonstrates that an evaluation of only reserve alkalinity is not sufficient to ensure the safety of these products. This preliminary work supports the rat as a potential model to assess the acute gastric irritation potential of alkaline formulations or substances.
Assuntos
Detergentes/toxicidade , Irritantes/toxicidade , Estômago/efeitos dos fármacos , Animais , Masculino , Modelos Biológicos , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Estômago/patologia , Toxicologia/métodosRESUMO
Groups of young, sexually mature Fischer-344 rats (n = 25/sex) obtained from commercial breeders were examined ophthalmologically and histopathologically to determine the prevalence and severity of corneal basement membrane lesions (corneal dystrophy) and basement membrane changes in select nonocular tissues. Results disclosed a high incidence of corneal basement membrane dystrophy in rats of both sexes from all breeders; however, severity levels were significantly increased in rats obtained from one breeder when compared to others. Furthermore, rats that displayed the most advanced corneal lesions also exhibited more severe basement membrane changes in other organs, especially renal tubules and vascular internal laminae. These findings suggest that both ocular and nonocular dystrophic changes may have been linked through common physiologic (or genetic) mechanisms. Animals that displayed basement membrane lesions were not considered to represent compromised biologic test systems.
Assuntos
Doenças da Córnea/patologia , Animais , Membrana Basal/patologia , Vasos Sanguíneos/patologia , Feminino , Rim/patologia , Masculino , Ratos , Ratos Endogâmicos F344 , Estômago/patologiaRESUMO
Groups of eight human volunteers and eight albino rabbits, under controlled laboratory conditions, were exposed in one eye without subsequent rinsing to the same concentrations and volumes of four prototype consumer products: fabric softener, shampoo, hand soap, and laundry detergent. Dose volume was 0.10 or 0.01 ml. The dose concentrations were selected to produce moderate effects with recovery within 24 to 48 hr. Two irritation scales were employed with both human and animal subjects: the Draize scale by a technician and a medical scale used with slit lamp examination by an ophthalmologist. Eyes were examined by both graders before and after dosing at specified intervals until recovery. Mean and maximum irritation scores are presented for each grading time, method, and exposure, as are the mean hours to recovery (clearing) for each exposure. Recovery times for human eyes were consistent with those reported previously for accidental human exposures to similar materials. Correlation coefficients for time to clear, comparing human vs rabbit for each dose volume-species combination across the four test products, were 0.72, 0.1 ml-human vs 0.01 ml-rabbit; 0.66, 0.01 ml-human vs 0.01 ml-rabbit; 0.40, 0.01 ml-human vs 0.1 ml-rabbit; 0.35, 0.1 ml-human vs 0.1 ml-rabbit. Thus, recovery time obtained under conditions of the "Low-Volume" test (0.01 ml-rabbit) better correlates with human eye recovery time (either dose volume) than does recovery time under Draize test conditions (0.10 ml-rabbit).(ABSTRACT TRUNCATED AT 250 WORDS)