Toxicological evaluation of some food
additives including anticaking agents,
antimicrobials, antioxidants, emulsifiers
and thickening agents
WHO FOOD ADDITIVES SERIES NO. 5
The evaluations contained in this publication
were prepared by the Joint FAO/WHO Expert
Committee on Food Additives which met in Geneva,
25 June - 4 July 19731
World Health Organization
Geneva
1974
1 Seventeenth Report of the Joint FAO/WHO Expert Committee on
Food Additives, Wld Hlth Org. techn. Rep. Ser., 1974, No. 539;
FAO Nutrition Meetings Report Series, 1974, No. 53.
ISOPROPYL CITRATE MIXTURE AND MONOISOPROPYL CITRATE
(monoisopropyl citrate 27%; diisopropyl citrate 9%; triisopropyl
citrate 2%; mono- and diglycerides 62%)
Explanation
These substances have been evaluated for acceptable daily intake
by the Joint FAO/WHO Expert Committee on Food Additives (see Annex 1,
Refs Nos 6 and 13) in 1961 and 1966.
The previously published monographs have been revised and are
reproduced in their entirety below.
BIOLOGICAL DATA
BIOCHEMICAL ASPECTS
Studies in the rat showed that isopropyl mixture was readily
absorbed when it was incorporated in the diet up to the 10% level
(Calbert et al., 1951).
TOXICOLOGICAL STUDIES
Acute toxicity
LD50
Animal Route (mg/kg bw) Reference
Rat oral 2 800-3 700 Deuel et al., 1951
Dog oral 2 250 Deuel et al., 1951
Short-term studies
Rat
A group of rats were fed isopropyl mixture in the diet at the
rate of 1500-2000 mg/rat per day for six weeks. There was no
demonstrable effect on growth or mortality, and there were no
pathological findings (Deuel et al., 1951).
Rabbit
A group of rabbits were fed isopropyl mixture at an average
level of about 3600 mg/rabbit per day for six weeks. There was no
demonstrable effect on growth or mortality and there were no abnormal
findings post mortem (Deuel et al., 1951).
Dog
A group of dogs were fed isopropyl mixture in the diet at the
level of 0.06% for six weeks with no demonstrable effect on growth or
mortality, and no pathological findings (Deuel et al., 1951).
Long-term studies
Rat
Groups of rats were fed isopropyl mixture in the diet at the
levels of 0%, 0.28%, 0.56% and 2.8% for a period of two years. No
deleterious effects were noted in any of the treated groups with
respect to growth rate, mortality or histopathology of the tissues
(Deuel et al., 1951).
Multigeneration studies likewise indicated that isopropyl mixture
at a level of 2.8% in the diet was innocuous (Deuel et al., 1951).
Comments:
No deleterious effects were observed in the short-term studies
in rats, rabbits and dogs, or in the long-term studies in rats.
Nevertheless, in view of the known toxicity of isopropyl alcohol,
it is necessary to set a value for an acceptable daily intake.
EVALUATION
Level causing no toxicological effect
Rat: 28 000 ppm (2.8%) of monoisopropyl citrate in the diet
equivalent to 1400 mg/kg bw.
Estimate of acceptable daily intake for man
0-14 mg/kg bw.*
REFERENCES
Calbert, C. E. et al. (1951) Food Res., 16, 294
Deuel, H. J. et al. (1951) Food Res., 16, 258
* Calculated as monoisopropyl citrate.