INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
WORLD HEALTH ORGANIZATION
TOXICOLOGICAL EVALUATION OF SOME
FOOD COLOURS, EMULSIFIERS, STABILIZERS,
ANTI-CAKING AGENTS AND CERTAIN
OTHER SUBSTANCES
FAO Nutrition Meetings Report Series
No. 46A WHO/FOOD ADD/70.36
The content of this document is the result of the deliberations of the
Joint FAO/WHO Expert Committee on Food Additives which met in Rome,
27 May - 4 June 19691
Food and Agriculture Organization of the United Nations
World Health Organization
1 Thirteenth report of the Joint FAO/WHO Expert Committee on Food
Additives, FAO Nutrition Meetings Report Series, in press;
Wld Hlth Org. techn. Rep. Ser., in press.
ACETYLATED DISTARCH ADIPATE
Modification is carried out by the use of five per cent acetic
anhydride and a maximum of 0.12 per cent. adipic acid, the latter
acting as cross-linking agent. The maximum number of acetyl groups
introduced is 2.5 per cent. The number of adipic cross-links does not
exceed more than one in about 1000 anhydroglucose units, or not more
than 0.09 per cent, adipyl groups introduced on the starch.
Biological Data
Biochemical aspects
In vitro studies with pancreatin have shown that only the acetate
ester bond splits easily while the adipic acid ester linkages are not
attached. No free adipic acid could be demonstrated in the hydrolysate
(Morgareidge, 1959a). The metabolic fate of adipate-modified starches
was therefore investigated in male rats in vivo using
adipate-modified labelled at C1 and C6 with C14. The rate of
appearance of 14CO2 was compared between starch modified with 1, 6
-C14 adipic acid and a physical mixture of untreated starch and
equivalent amounts of 1, 6 - C14 adipic acid. Starch adipate is
absorbed and/or metabolised more slowly as shown by the delayed
appearance of 14 CO2 in the respired air. Almost all the C14
activity of the free adipic acid was recovered in the respired air;
only a small amount appeared in the urine while none was detected in
the faeces, in the gastro-intestinal tract or in the carcass. More
than half of the C14 activity of the etserified adipic acid appeared
in the respired air and a proportionate amount in the urine, the rest
was found in the faeces. No activity appeared in the carcass
(Morgareidge, 1959b). The caloric equivalent of the modified starch
was determined in groups of 10 male rats fed for 28 days on a basal
diet containing either 1.5 or 3.0 g of starch supplements. The
modified starch had been treated with 0.2 per cent. adipic anhydride
and 5.5 per cent. acetic anhydride. Native starch was used as control.
Caloric values were determined from a dose/response curve obtained by
the use of 0, 0.75 g, 1.5 g, 3.0 g and 4.5 g of sucrose supplements
equivalent to 0, 3, 6, 12 and 18 calories per day. There was no
difference in caloric value as between the modified and unmodified
starches (Oser, 1961).
Acute toxicity
None available.
Short-term studies
Rat. A 90-day feeding study was carried out in groups of 15 male and
15 female rats at a dietary level of 50 per cent. modified or
unmodified starch. The growth rate of males was significantly lower in
the test group and the full and empty caecal weights of both sexes
were significantly greater in rats fed the treated starch. All rats
survived the test period and no differences were observed between the
groups in respect of liver and kidney weights, haematology, blood
chemistry, urinalysis, gross and histopathology. The modified starch
used had been treated with 0.12 per cent. adipic acid and 10.5 per
cent. acetic anhydride resulting in 3.1 per cent. of acetyl groups
being present (Oser, 1964).
Long-term studies
None available.
Comments
The metabolic studies show that adipate cross-linking interferes with
enzymatic breakdown and possibly delays absorption. A study with the
C14 labelled material showed that the moiety containing the adipic
acid was metabolized normally more slowly. No retention of label was
found in the carcass. The available 90-day studies were only done at
one dose level and do not establish a no-effect level although the
pathological findings appear to be related only to the acetylation.
Estimation of the acceptable daily intake may be based on the
no-effect level for rats for acetylated starch.
EVALUATION
Levels showing no toxicological effect in the rat (for starch acetate)
Five per cent. (= 50 000 ppm) in the diet equivalent to 2500 mg/kg
body weight/day.
Estimate of acceptable daily intake for man
Temporary acceptance mg/kg body weight
0 - 12.5
Further work required by June 1974
Adequate 90-day studies in two species (one a non-rodent mammal).
REFERENCES
Morgareidge, K. (1959a) Unpublished report No. 78522 by Food and Drugs
Research Laboratories Inc., 30th November 1959 submitted by National
Starch and Chemical Corporation
Morgareidge, K. (1959b) Unpublished report No. 79408 by Food and Drugs
Research Laboratories Inc., 28th October 1959 submitted by National
Starch and Chemical Corporation
Oser, M. (1961) Report No. 81776 by Food and Drugs Research
Laboratories Inc., Ist June 1961 submitted by National Starch and
Chemical Corporation
Oser, B. L. (1964) Report No. 85555 by Food and Drugs Research
Laboratories Inc., 16th October 1964 submitted by National Starch and
Chemical Corporation