WORLD HEALTH ORGANIZATION
WHO Food Additives Series 1972, No. 1
TOXICOLOGICAL EVALUATION OF SOME
ENZYMES, MODIFIED STARCHES AND
CERTAIN OTHER SUBSTANCES
The evaluations contained in this publication were prepared by the
Joint FAO/WHO Expert Committee on Food Additives which met in Rome,
16-24 June 19711
World Health Organization
Geneva
1972
1 Fifteenth Report of the Joint FAO/WHO Expert Committee on Food
Additives, Wld Hlth Org. techn. Rep. Ser., 1972, No. 488; FAO
Nutrition Meetings Report Series, 1972, No. 50.
The monographs contained in the present volume are also issued by the
Food and Agriculture Organization of the United Nations, Rome, as FAO
Nutrition Meetings Report Series, No. 50A
(c) FAO and WHO 1972
MICROCRYSTALLINE CELLULOSE
Biological data
Biochemical aspects
Four rats were fed 14C-labelled microcrystalline cellulose at 10 and
20 per cent. of their diet. No evidence of degradation or digestion
was noted. Faecal recoveries of radioactivity ranged from 96-104 per
cent. and were complete for all labelled material. No radioactivity
appeared in the urine (Baker, 1966). One human subject received 150 g
of 14C-labelled microcrystalline cellulose (47.6 µc) in two portions
on one day and 150 g unlabelled micro crystalline cellulose daily for
the subsequent 10 days. Twenty-four hour faecal and urine collections
were examined for radio activity. No radioactivity appeared in the
urine or in the expired CO2. All administered radioactivity was
recovered from the faeces within 2 days. (Baker, 1968.) Examination
of the stools of 1 male and 1 female patient given 30 g
microcrystalline cellulose as dry flour or gel for 5-1/2 weeks showed
the presence of undegraded material of the same birefringence as the
original microcrystalline cellulose administered. No significant
effects on the human gastro-intestinal tract were noted during the
administration (Tusing et al., 1964).
Acute toxicity
mg/kg
Animal Sex Route body-weight Reference
Rat male oral >3160 Hazleton Labs., 1959
Rat male i.p. >3160 " " "
Short-term studies
Rat
Groups of 4 male rats were kept on diets containing 0.25, 2.5 or 25
per cent. of various edible celluloses for three months. No
differences were observed among the groups with regard to growth and
faecal output. Histopathology of the gastro-intestinal tract revealed
no treatment-related abnormalities (Frey et al., 1928).
Three groups of 5 male rats received 0, 5 or 10 per cent.
microcrystalline cellulose in their diet for 8 weeks. Growth was
comparable to the controls but the 10 per cent. group showed slightly
lower body-weights. Haematology, serum chemistry and vitamin B,
levels in blood and faeces showed no differences from the controls
(Yoshitoshi Internal Seminar, 1966).
Long-term studies
Rat
Three groups of 50 male and 50 female rats received in their diet for
72 weeks either 30 per cent. ordinary cellulose or dry
microcrystalline cellulose or microcrystalline cellulose gel.
Appearance and behaviour was comparable in all groups. No adverse
effects were noted. The body-weights of males given microcrystalline
cellulose gel were higher than those of the controls. Food
efficiency, survival and haematology were comparable in all groups.
The liver and kidney weights of males receiving microcrystalline
cellulose gel were higher than the controls. Gross and histopathology
showed some dystrophic calcification of proximal renal tubules in
females on microcrystalline cellulose but all other organs appeared
unremarkable. Tumour incidence did not differ between the groups
(Hazleton Laboratories, 1963).
Reproduction studies
Rat
Groups of 8 male and 16 female rats were used to produce a P, F1A,
F1B, F2 and F3 generation after having been fed on diets
containing 30 per cent. of microcrystalline cellulose flour or gel or
ordinary cellulose as a control. The presence in the diet of such an
amount of non-nutritious material, which contributed no calories had
an adverse effect on reproduction. Fertility and numbers of live pups
were relatively depressed and lactation performance in all three
generations, as well as survival and the physical condition of the
pups, were unsatisfactory throughout the study. The new-born pups
appeared smaller, weak and showed evidence of disturbed motor
co-ordination. Liver weights were increased in the group receiving
microcrystalline cellulose gel in all generations but other organ
weights showed no consistent patterns. Gross and histopathology
revealed renal changes similar to those seen in the feeding study in
females of all generations. Other organs showed no consistent
changes. No teratological deformities were seen (Hazleton
Laboratories, 1964).
Observation in man
A number of clinical studies using refined cellulose as roughage in
human diet for the treatment of constipation showed no deleterious
effects. Groups of 18 children received regular amounts of edible
cellulose instead of normal cereal for 3 months. The only effect
noted was an increase in bowel movements but no diarrhoea or other
gastro-intestinal disturbances were seen (Frey et al., 1928).
Eight male and 8 female volunteers supplemented their normal diet with
30 g microcrystalline cellulose per day either as dry powder or gel
(15 per cent. aqueous) for 6 weeks followed by 2 weeks without
supplementation. No adverse findings were reported regarding
acceptance or body-weight but most subjects complained of fullness and
mild constipation. Haematology was normal in all subjects.
Biochemical blood values showed no differences between treatment and
control periods, nor was there evidence of liver or kidney function
disturbance. Urinalysis produced normal findings. The faecal flora
remained unchanged. The cellulose content of faeces increased 5-8
times during the test period. Microscopy revealed the presence of
microcrystalline cellulose (Hazleton Laboratories, 1962).
In another study 8 healthy males received 30 g microcrystalline
cellulose daily as supplement to their diet for 15 days. D-zylose
absorption varied between pre-test, test and post-test periods being
lower during microcrystalline cellulose ingestion. The absorption of
I131-triolein was unaffected by microcrystalline cellulose ingestion.
No change was noted in the faecal flora nor was there any significant
effect on blood chemistry during ingestion of microcrystalline
cellulose. Examination of urine, blood and faecal levels of vitamin B,
during microcrystalline cellulose ingestion showed no difference from
control periods (Yoshitoshi Internal Seminar, 1966).
Comments
The animal and human studies including the use of radio-labelled
material show complete absence of digestion or absorption.
Microcrystalline cellulose is structurally very close to naturally
occurring cellulose. Doses up to 30 g per day appear to be tolerated
therapeutically as bulk laxative. The adverse effects reported in the
long-term studies are probably attributable to the inadequacies of a
diet containing a large amount of indigestible material.
EVALUATION
Acceptable daily intake for man
No limit.*
REFERENCES
Baker, E. M. (1966) Unpublished report of F.M.C. Corporation
Baker, E. M. (1968) Unpublished report of F.M.C. Corporation
* Except for good manufacturing practice.
Frey, J. W., Harding, E. R. & Helmbold, T. R. (1928) Med. J. Rec.,
June, 585
Hazleton Laboratories Inc. (1959) Unpublished report submitted by
American Viscose Corporation
Hazleton Laboratories Inc. (1962) Unpublished report submitted by
American Viscose Corporation
Hazleton Laboratories Inc. (1963) Unpublished report submitted by
American Viscose Corporation
Hazleton Laboratories Inc. (1964) Unpublished report submitted by
American Viscose Corporation
Tusing, T. W., Paynter, O. E. & Battista, O. A. (1964) Agric. Fd.
Chem., 12, 284
Yoshitoshi Internal Seminar (1966) Unpublished report submitted by
Asaki Chemical Industry Co. Ltd.
See Also:
Toxicological Abbreviations
Microcrystalline cellulose (WHO Food Additives Series 5)
Microcrystalline cellulose (WHO Food Additives Series 40)
MICROCRYSTALLINE CELLULOSE (JECFA Evaluation)