RESUMO
The reproductive effects of the administration of 4-chloro-2-methylphenoxyacetic acid (MCPA) to rats were evaluated through two generations, from prior to mating, throughout mating, to gestation and lactation. MCPA was administered in the diet at doses of 0, 50, 150, or 450 ppm to 25 male and female immature rats (F0 parents) for 10 weeks. F0 parents were then mated to produce a first litter (F1a), retained only until weaning, and were subsequently remated to produce a second litter, F1b. Groups of male and female F1b animals were then dosed as were their parents for 10 weeks postweaning, and the breeding was repeated to produce F2a and F2b animals. The study concluded with the F2b weanlings. MCPA was administered continuously throughout the study. Only minimal, non-treatment-related observations were noted, which included rhinorrhea (in both treated and control animals in the F0 generation) and malocclusion and alopecia (in both the F0 and F1b generations). There were no consistent dose-related effects on reproductive function for parental animals of either sex in either generation. Statistically significant differences were noted in body weights and body weight gains in the 450-ppm dose group for both male and female pups in F2a and F2b. There were no treatment-related macroscopic or microscopic observations noted for any animal in this study. The no-observable-effect level (NOEL) for reproductive function in rats administered MCPA continuously for two successive generations was determined to be 450 ppm (approximately 22 mg/kg/day). The NOEL for general systemic toxicity, based on body weight effects in adult animals in the F1b generation was 150 ppm. The NOEL for effects on the offspring of the F1b generation, manifested as reduced pup weights and pup weight gains was also 150 ppm (approximately 8 mg/kg/day). Based upon the results of this study, MCPA, administered for two generations to Crl:CD(SD)BR Albino rats, is considered not to be a reproductive toxicant.
Assuntos
Ácido 2-Metil-4-clorofenoxiacético/toxicidade , Herbicidas/toxicidade , Reprodução/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Lactação/efeitos dos fármacos , Tamanho da Ninhada de Vivíparos/efeitos dos fármacos , Masculino , Nível de Efeito Adverso não Observado , Ratos , Aumento de Peso/efeitos dos fármacosRESUMO
The chronic toxicity and oncogenicity of 4-chloro-2-methylphenoxyacetic acid (MCPA) were evaluated in Wistar rats at target doses of 20, 80, and 320 ppm for 2 years. Chronic effects were noted in male and/or female rats in the 80- and 320-ppm dose groups, namely elevations in triglycerides and serum glutamic transaminase levels. Nephrotoxicity was confined to male rats in the 320-ppm dose group. The systemic NOEL was determined to be 20 ppm for male and female rats. No oncogenic potential was observed. Doses in the 2-year oncogenicity study in mice were 20, 100, and 500 ppm. Kidney weight changes with corresponding minor histopathological findings in the kidney were evident in females in the 500-ppm dose group. MCPA was determined to have no oncogenic potential in B6C3F1 mice. In summary, there is no evidence of any oncogenic potential after dietary exposure of MCPA in rats or mice even at doses where limited chronic toxicity is seen.
Assuntos
Ácido 2-Metil-4-clorofenoxiacético/toxicidade , Carcinógenos/toxicidade , Herbicidas/toxicidade , Alanina Transaminase/sangue , Animais , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Rim/efeitos dos fármacos , Rim/patologia , Masculino , Camundongos , Neoplasias Experimentais/induzido quimicamente , Neoplasias Experimentais/patologia , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Wistar , Análise de Sobrevida , Triglicerídeos/sangueAssuntos
Inseticidas , Peróxidos , Amidas , Benzoatos , Estabilidade de Medicamentos , Fonofos , Radicais Livres , Indóis , Malation , Microssomos/enzimologia , Modelos Químicos , Nitrilas , Oxirredução , Oxirredutases/metabolismo , Oximas , Paraoxon , Paration , Ácido Fenilfosfonotioico, 2-Etil 2-(4-Nitrofenil) Éster , Ácidos Fosfóricos , Pirimidinas , EnxofreRESUMO
4-Isopropyl-2,6,7-trioxa-1-phosphabicyclo[2.2.2]octane 1-oxide has a mouse intraperitoneal lethal dose, 50 percent effective, of 0.18 milligram per kilogram of body weight. Related compounds used by many chemical researchers are also highly toxic. Brain acetylcholinesterase inhibition is not involved in their mode of action. The structural similarity of these compounds to adenosine 3',5'-monophosphate (cyclic AMP) is of interest.