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.
PROPYLENE CHLOROHYDRIN
Biological Data
Biochemical aspects
Wesley et al. (1965) identified propylene chlorohydrin as the residue
formed in foods fumigated with propylene oxide. The chlorohydrin is
formed by the reaction of the epoxide with the chloride of food.
Previously, it had been believed that propylene glycol, formed by
reaction with water in the food, was the residue. Propylene
chlorohydrin is also formed in starches modified by
hydroxypropylation. Both propylene chlorohydrin isomers have been
identified in fumigated foods (Ragelis et al. 1966).
When volatilization was precluded, a combination of high temperature
and prolonged time in cooking did not appreciably alter the propylene
chlorohydrin content of food, but when volatilization was possible,
the chlorohydrin content was reduced 50 per cent. by cooking (Wesley
et al. 1965). When propylene chlorohydrin was added to a standard
ground laboratory rat diet, 20 minutes of mixing in an open mixer at
room temperature resulted in a 65 per cent. decrease in the propylene
chlorohydrin content (USFDA, 1966).
Acute toxicity
Animal Route LD50 Reference
(mg/kg body weight)
Rat oral 218 USFDA, 1969
Dog oral 150 mg/kg - no deaths USFDA, 1969
200 mg/kg - 1/7 deaths
250, 300 mg/kg - 6/6 deaths
Short-term toxicity
Rat. Groups of 10 male and 10 female five-week-old rats were fed,
for 25 weeks, diets to which propylene chlorohydrin had been added.
The planned dietary levels were 0, 1000, 2500, 5000, and 10 000 ppm,
but analysis of the 10 000 ppm diet after mixing in the test compound
(open mixer, 20 minute mixing time, room temperature) showed an actual
concentration of 3568 ppm or 35 per cent. of the planned level. The
2-chloro isomer constituted 27 per cent. of the total found. The
actual level in this diet, after seven days exposure to laboratory
conditions, was reduced to 838 ppm, with 32 per cent. of the 2-chloro
isomer, or less than 10 per cent. of the planned concentration.
Weight gain in both sexes on the 5000 and 10 000 ppm levels was
depressed. The depression was slight in the males on the 5000 ppm
level and both groups of females and moderate in the males on the 10
000 ppm level. Food consumption was slightly decreased in these groups
but food efficiency was normal. The average liver, and kidney weights
of the males and the liver weight of the females on the 10 000 ppm
level were decreased but the organ weight/body weight ratios were
normal. The decreased spleen weights and spleen/body weight ratios
in the males and other minor organ weight variations appeared to be
unrelated to the treatment. No effects on haematological values,
mortality, or gross or microscopic lesions in the tissues were
observed (USFDA, 1969).
Propylene chlorohydrin was administered to groups of 10 male and 10
female eight-week old rats by stomach tube in doses of 0, 25, 50, 75,
and 100 mg/kg/day for 22 weeks. The dose for the high level was
increased from 100 mg/kg to 150 mg/kg in the eleventh week, to 200
mg/kg in the fourteenth week, and to 250 mg/kg in the sixteenth week.
Doses of 200 mg/kg and less did not increase mortality. All the rate
on the high level were dead by the nineteenth week with all but one of
the deaths occurring between the sixteenth and nineteenth weeks after
the dose had been increased to 250 mg/kg. On the high level, weight
gain was moderately depressed in the males and slightly depressed in
the females while the dose was 100 or 150 mg/kg. Both sexes lost
weight when the dose was increased to 200 mg/kg. Weight gain was
slightly, but not significantly, decreased in both sexes on the 75
mg/kg level. Food consumption was slightly decreased in the males of
the high level while the dose was 100 mg/kg and decreased to a greater
extent when the dose was raised. The females on the high level also
showed a slight decrease in food consumption when the dose was
increased. With the rats losing weight when the dose was increased to
200 mg/kg, the food efficiency values have no meaning. The liver
weight/body weight ratios of both males and females on the 75 mg/kg
dose and the liver weight and liver weight/body weight ratio of the
males on the 25 mg/kg dose were increased, but this increase was not
accompanied by gross or microscopic alterations in the liver. Other
organ weight and organ weight/body weight ratio changes did not appear
to be related to the treatment. No haematological effects or gross or
microscopic effects on the tissues of the treated rats, at a dose of
75 mg/kg or less, were seen. The tissues of the high level rats were
not examined microscopically (USFDA, 1969).
Comments
Although in vitro enzymatic digestion tests revealed no
abnormalities there was some evidence that a high degree of
substitution rendered the product less digestible at the 25 per cent.
dietary level. The 90-day tests are adequate and point to 10 per cent.
in the diet as the no-effect level. Information is desirable on the
metabolic behaviour preferably in man - of the moiety containing the
propylene glycol ether.
EVALUATION
Level causing no toxicological effect in the rat
Ten per cent, (= 100 000 ppm) in the diet equivalent to 5000 mg/kg
body weight/day.
Estimate of acceptable daily intake for man
Temporary acceptance mg/kg body weight
0 - 25
Further work required by June 1972
Ninety-day tests in a non-rodent mammalian species using material
modified to the highest degree employed as food additive.
REFERENCES
Feron, V. J., Til, H. P. & de Groot, A. P. (1967) Unpublished report
by Centraal Instituut voom Voedings anderzoek TNO, No. R2456
Kay, J. H. & Calandra, J. C. (1961) Unpublished report by Industrial
Bio-Test Laboratories, Inc. 17th November 1961
Kay, J. H. & Calandra, J. C. (1962) Unpublished report by Industrial
Bio-Test Laboratories, Inc. 22nd January 1962
Majors, P. A. & Rubenkoenig, H. L. (1959) Unpublished report by Hill
Top Research Institute, Inc. 18th May 1959
Pallotta, A. J. (1959) Unpublished report by Hazleton Laboratories,
Inc. 22nd May 1959
Ragelis, E. P., Fisher, B. S. & Klimeck, B. A. (1966) J.O.A.C., 49,
963
Rubenkoenig, H. L. (1959) Unpublished report by Hill Top Research
Institute, Inc. 13th May 1959
United States Food and Drug Administration (1969) Unpublished data
Wesley, F., Rourke, B. & Darbishire, O. (1965) J. Fd. Sci., 30, 1037