Synergistic Toxicity of Official Permissible Preservative Food Additives

In an investigation of the synergistic toxicity of officially permitted preservative food additives, the acute toxicity test and six-months breeding test were used. Part 1. (Acute toxicity test) (1) Ten preservatives were chosen from the officially permitted list: (sodium dehydroacetate, sorbic acid, benzoic acid, ethyl p-hydroxybenzoate, propyl p-hydroxybenzoate, butyl p-hydroxybenzoate, salicylic acid, sodium propionate, furylfuramide…2%, furylfuramide…pure). Mixtures of two additives each were administered orally to dd mice. (2) Mixtures were made in two ways: eqaul amounts of each ingredient and eqaul LD50 doses of each. (3) In order to evaluate the synergistic toxicity of the mixtures, the theoretical LD50 values of the mixtures were caliculated. (4) The toxicity of the mixtures was found not to exceed the theoretical values; i.e., it was not synergistic. Part 2. (Six-months breeding test) (1) From the preservatives listed in part 1, furylfuramide…2% (F), sorbic acid (S) and ethyl p-hydroxybenzoate (E) were chosen and administered as single doses and in pairs to SD-JCL rats for 25 weeks. (2) The amounts administered corresponded to about 1/5, 1/10 and 1/50 of the LD50. The percentages of preservatives in the diet were: (F) 4.0%, 2.0%, 0.4%; (S) 3.0%, 1.5%, 0.3%; (E) 2.0%, 1.0%, 0.2%. (3) Experimental results. 1) During the experimental period, no significant difference was noted in the general appearence, behavior, food consumption, mortality or mean survival times between the experimental and control groups. 2) The weight gain was normal except for a slight delay in the F4%-E2% group. 3) The red blood cell count hemoglobin, hematocrit and white blood cell count were not affected. 4) The results of biochemical serum tests were as follows: the males in groups F4%, F4%-S3%, F2%-S1.5%, and the females in groups F4%, F2%-S1.5%, F0.4%-S0.3%, F4%-E2% and F2%-E1% showed significantly higher total protein and total cholesterol than the control group. 5) The F4% and F4%-E2% groups tended to have enlarged livers and kidneys, and F4%-S3%, F2%-S1.5% and F2%-E1% groups tended to have enlarged livers only. 6) Pathological examinations showed no abnormal findings either macroscopically or microscopically. (4) These experiments showed no significant synergistic toxicity in mixtures of the above-mentioned food preservatives.