RESUMEN
Most sciences and technologies related to food safety have advanced exponentially over the 40 years since passage in the U.S. of the Food Additive Amendment of 1958 to the Federal Food, Drug and Cosmetic (FD&C) Act. Effective regulatory decision making places a high premium on competent professional and administrative judgement applied to sound scientific data. This review discusses changes and lessons learned in the food safety sciences over the last 4 decades. Other segments of the safety and compliance infrastructure necessary to assure that the public receives safe and wholesome foods have not kept pace with the new scientific knowledge. The quality of foods in our marketplace can be improved only after the regulatory and legislative segments of the infrastructure, discussed in a companion symposium paper, are brought into better synchrony with the sciences.
Asunto(s)
Análisis de los Alimentos , Tecnología de Alimentos , Legislación Alimentaria , Agricultura , Aditivos Alimentarios/química , Aditivos Alimentarios/toxicidad , Etiquetado de Alimentos , Tecnología de Alimentos/tendencias , Humanos , Relación Estructura-Actividad , Estados Unidos , United States Food and Drug AdministrationRESUMEN
In preparation for the design and performance of chronic toxicity and carcinogenicity studies in rats and mice on dichloromethane (methylene chloride; DCM), biochemical, mutagenicity, short-term, metabolic and subchronic feeding studies were carried out. These studies established that it was feasible to present DCM to rodents at adequate levels in drinking-water. Saturation of metabolic pathways was demonstrated in both rats and mice at oral doses of approximately 100 mg/kg. The lowest toxic effect levels after 90 days of treatment were found to be approximately 190 and 580 mg/kg for rats and mice, respectively. Dose, vehicle and the exposure regimen were found to affect DCM challenge to target tissues and its metabolism to CO and CO2.
Asunto(s)
Radioisótopos de Carbono , Hidrocarburos Clorados/metabolismo , Cloruro de Metileno/metabolismo , Absorción , Administración Oral , Animales , Autorradiografía , Pruebas Respiratorias , Monóxido de Carbono/análisis , Femenino , Cinética , Neoplasias Hepáticas/inducido químicamente , Masculino , Concentración Máxima Admisible , Cloruro de Metileno/toxicidad , Cloruro de Metileno/orina , Ratones , Ratas , Ratas Endogámicas F344 , Distribución TisularRESUMEN
In order to evaluate its toxicity and carcinogenic potential, dichloromethane (DCM) at levels of 0, 0, 5, 50, 125 and 250 mg/kg body weight/day was administered in deionized water to a total of 500 Fischer 344 rats of each sex for 104 wk. An additional group received a level of 250 mg/kg body weight/day for 78 wk followed by a 26-wk recovery period during which only deionized water was presented. Kills were performed at 26-wk intervals. Statistically significant effects on body weight, water consumption and food consumption were observed at the two highest dose levels. Minimal effects were noted on the haematological and serum chemistry parameters monitored. Treatment-related hepatic changes were observed histomorphologically in both sexes after 78 wk of treatment. These changes consisted of an increased incidence of foci/areas of cellular alteration and of fatty change at all dose levels except the lowest. A decrease in the severity of fatty change was observed in the recovery group, but no difference was noted in the incidence of cellular alteration. An increased incidence of hepatic tumours noted in females treated at 50 and 250 mg/kg/day was within the range of historical control incidences. In view of an unusually low incidence of similar tumours in the concurrent control groups and the absence of an increased incidence of hepatic tumours in the group treated at 125 mg/kg/day, the effect seen at 50 and 250 mg/kg/day was not considered to be attributable to DCM treatment. Under the experimental conditions of this study, there was a no-observable-effect level of 5 mg/kg/day in both males and females.
Asunto(s)
Hidrocarburos Clorados/toxicidad , Neoplasias Hepáticas/inducido químicamente , Cloruro de Metileno/toxicidad , Administración Oral , Animales , Sangre/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Femenino , Neoplasias Hepáticas/patología , Masculino , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Endogámicas F344RESUMEN
To investigate its carcinogenic potential, dichloromethane (DCM) was administered at levels of 0, 0, 60, 125, 185 and 250 mg/kg body weight/day to a total of 1000 B6C3F1 mice in deionized drinking-water for 104 wk. The high-dose male and female mice showed a transitory increase in mean leucocyte counts. Treatment-related toxic changes were noted in both male and female livers at the highest dose. There was a slight elevation of proliferative hepatocellular lesions in the treated males but no dose-related trend was apparent and the effect was absent in the females. Neoplastic lesions observed in the study were homogeneous among all groups and were within the range of incidence in historical controls. The results of this study demonstrated a toxicological no-observable-effect level (NOEL) for DCM of 185 mg/kg body weight/day in both sexes.
Asunto(s)
Hidrocarburos Clorados/toxicidad , Neoplasias Hepáticas/inducido químicamente , Cloruro de Metileno/toxicidad , Administración Oral , Animales , Peso Corporal/efectos de los fármacos , Femenino , Recuento de Leucocitos/efectos de los fármacos , Neoplasias Hepáticas/patología , Masculino , RatonesRESUMEN
The toxicological testing of the millions of known chemicals or even the thousands of food components is not practical at present. Therefore, priorities for testing should be set carefully, to ensure that primary attention is given to materials for which risk management can potentially improve public health. Most flavouring materials used today by the food industry occur widely in natural and traditional foods. A proposed Consumption Ratio (CR) relates the amount of a flavouring material found in natural and traditional foods to the amount added to food by food processors. A CR above 1 means that the consumption of the flavouring material takes place predominantly via traditional food. High CR values should establish that the priority ranking for testing these flavouring substances needs to be no higher than that for testing the complete foods.
Asunto(s)
Aromatizantes , Aditivos Alimentarios , Animales , Humanos , Sociedades Científicas , Estados UnidosRESUMEN
Carmoisine (C.I. (1956) No. 14720) was fed at levels of 0, 0.35, 0.8 and 2.0% in the diet of rats throughout a multigeneration reproduction study. The dye had not untoward effects on reproduction capacity of any of the generations studied. Fertility, lactation and viability indices of all groups fed carmoisine did not differ significantly from controls at any stage of the study. These results indicate a maximum no-effect level of 2% in the diet. Data from an additional nine-week feeding study (dietary levels were 0, 2, 4, 6 and 8%) suggest that the no-effect level may in fact be even higher since 4% carmoisine in the diet was tolerated without evidence of overt toxicity.
Asunto(s)
Compuestos Azo/farmacología , Colorantes/farmacología , Colorantes de Alimentos/farmacología , Naftalenosulfonatos/farmacología , Reproducción/efectos de los fármacos , Animales , Peso al Nacer/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Copulación/efectos de los fármacos , Dieta , Femenino , Fertilidad/efectos de los fármacos , Muerte Fetal/inducido químicamente , Masculino , Embarazo , RatasRESUMEN
Rat fed carmoisine (C.I. (1956) No. 14720) at 0.35, 0.8 or 2.0% in the diet for 52 weeks showed no adverse effects of the dye when compared to control animals. Mortality, weight gain, hematological values and relative organ weights were the same in control and treated animals. There was no increase in tumor incidence due to carmoisine treatment. Male rats fed 2.0% carmoisine showed an increased incidence of several mild subclinical conditions (minimal bronchitis and tracheal inflammation). Because of this occurrence, the maximum no-effect level after 1 year exposure appears to be 0.8%, equivalent to a daily intake of approx. 400 mg/kg.