INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
WORLD HEALTH ORGANIZATION
TOXICOLOGICAL EVALUATION OF SOME
FOOD COLOURS, ENZYMES, FLAVOUR
ENHANCERS, THICKENING AGENTS, AND
CERTAIN FOOD ADDITIVES
WHO FOOD ADDITIVES SERIES 6
The evaluations contained in this publication were prepared by the
Joint FAO/WHO Expert Committee on Food Additives which met in Rome,
4-13 June 19741
World Health Organization Geneva 1975
1 Eighteenth Report of the Joint FAO/WHO Expert Committee on
Food Additives, Wld Hlth Org. techn. Rep. Ser., 1974, No. 557.
FAO Nutrition Meetings Report Series, 1974, No. 54.
MICROBIAL RENNET* (Mucor miehei)
Explanation
This enzyme preparation has been evaluated for acceptable daily
intake by the Joint FAO/WHO Expert Committee on Food Additives (see
Annex 1, Ref. No. 27) in 1971.
Since the previous evaluation additional data have become
available and are summarized and discussed in the following monograph.
The previously published monograph has been expanded and is reproduced
in its entirety below.
BIOLOGICAL DATA
BIOCHEMICAL ASPECTS
No information available.
TOXICOLOGICAL STUDIES
Special studies on teratogenicity
Rat
Groups of 19 or 20 pregnant rats received either 74, 148 or
276 mg/kg agent by gavage from day 6 to 15 of pregnancy. Animals were
sacrificed on day 20. No adverse effects were seen in pregnant dams.
Litter parameters were unaffected except for mean pups weight which
was slightly increased at the highest dose-level.
The fetal anomalies observed were unrelated to administration of
the test compound. No skeletal abnormalities were seen (Palmer &
Lovell, 1970).
Acute toxicity
None available.
* This enzyme preparation is prepared from the species Mucor
miehei.
Short-term studies
Rat
Four groups of 25 male and 25 female rats received in their diet
0, 0.1, 0.5 and 2.5% of microbial rennet (equivalent to 0, 100, 500
and 2500 units/kg/day) for one year. Appearance and behaviour
was normal throughout the experiment. Survival was comparable
in all groups and the few deaths observed were unrelated to the
administration of the test substance. Mean body weight and food
consumption were similar to controls. Haematology, blood chemistry and
urinalysis showed nothing significant compared with controls. Relative
organ weights, gross and histopathology showed nothing of note
(Gesler, 1970).
In another experiment groups of 20 male and 20 female rats
received in their diet 0, 0.5, 1.5 and 5% of microbial rennet for one
year. At the highest level of administration there was a small dose-
related reduction in body weight gain in the males and in the females
a slight reduction at the 1.5% level. No effect on food intake or
conversion. At the 1.5% level there was very slight reduction in food
intake of males only. Behaviour, appearance, urinalysis, haematology,
gross and micropathology were normal (Wheldon et al., 1970).
Dog
Four groups of five male and five female beagles received
by daily gavage six times a week for one year either 0, 500 or
2500 units/kg bw. Apart from some vomiting early in the study and
occasional vomiting in the highest test group there was no further
difficulty in administration. Behaviour, appearance, food consumption
and mean body weight did not differ from controls. Haematology, blood
chemistry, blood coagulation studies and urinalysis revealed no
changes due to the administration of the test substance. Mean relative
organ weights, gross and histopathology revealed no changes different
from controls (Gesler, 1970a).
Four groups of four male and four female beagles received 0,
5000, 15 000 or 50 000 ppm of rennet in their diet for one year. No
adverse effects due to the test compound were quoted as regards
mortality, appearance, body weight, ophthalmoscopy, clinical
biochemistry, haematology, and urinalysis, gross and micropathology
revealed nothing abnormal (Noel et al., 1970).
Long-term studies
Rat
Groups of 20 males and 20 females received orally 100 mg/kg bw of
active material for 24 months. No contemporary controls were used but
reliance was placed on the known history of the colony. Conditions
were not SPF and animals also received other agents and pesticides.
Body weight gain was normal, six animals dying during the 24 months.
Among 17 male survivors six had chronic bronchopneumonia, two had
fatty liver, two had testicular atrophy and none had any tumours.
Among 17 female survivors one benign fibroadenoma of the breast and
one pulmonary tumour were seen. Three animals had chronic
bronchopneumonia. There were other scattered lesions unrelated to
treatment. One male and five females were mated and produced a normal
litter of which five males and five females were treated with the
agent for seven months and mated again to produce a second generation.
No obvious gross abnormalities were seen (Mosinger, 1972).
Comments:
The available studies in two species including the long-term
study in the rat reveal no adverse effects at 2.5% in the rat on
100 mg/kg bw. The levels used would have revealed any deleterious
effects due to mycotoxins. This meets with the requirements laid down
by the Committee.
EVALUATION
Acceptable daily intake not specified.*
REFERENCES
Gesler, R. M. (1970) Unpublished report submitted by Travenol
Laboratories Inc.
Gesler, R. M. (1970a) Unpublished report submitted by Travenol
Laboratories Inc.
Mosinger, M. (1972) Report No. 730J02 to Novo Laboratories
Noel, P. R. B. et al. (1970) Report 3530/70/342 by HRC dated
20.10.1970 submitted to Novo Laboratories
* The statement "ADI not specified" means that, on the basis of the
available data (toxicological, biochemical, and other), the total
daily intake of the substance, arising from its use or uses at the
levels necessary to achieve the desired effect and from its acceptable
background in food, does not, in the opinion of the Committee,
represent a hazard to health. For this reason, and for the reasons
stated in individual evaluations, the establishment of an acceptable
daily intake (ADI) in mg per kg of body weight is not deemed
necessary.
Palmer, A. K. & Lovell, M. R. (1970) Report 3578/70/390 by HRC dated
6.10.70 submitted to Novo Laboratories
Wheldon, G. H. et al. (1970) Report by HRC dated 22 October 1970
submitted to Novo Laboratories