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.
MICROCRYSTALLINE CELLULOSE
Explanation
This substance 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.
The previously published monograph has been revised and is
reproduced in its entirety below.
BIOLOGICAL DATA
BIOCHEMICAL ASPECTS
Four rats were fed 14C-labelled microcrystalline cellulose at
10 and 20% of their diet. No evidence of degradation or digestion was
noted. Faecal recoveries of radioactivity ranged from 96 to 104% 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 microcrystalline cellulose daily for the
subsequent 10 days. Twenty-four hour faecal and urine collections were
examined for radioactivity. No radioactivity appeared in the urine or
in the expired CO2. All administered radioactivity was recovered from
the faeces within two days (Baker, 1968). Examination of the stools of
one male and one 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
gastrointestinal tract were noted during the administration (Tusing et
al., 1964).
TOXICOLOGICAL STUDIES
Special studies on reproduction
Rat
Groups of eight 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% 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
coordination. 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 (Hazelton Laboratories, 1964).
Acute toxicity
Animal Sex Route mg/kg bw Reference
Rat male oral > 3160 Hazelton Labs., 1959
Rat male i.p. > 3160 Hazelton Labs., 1959
Short-term studies
Rat
Groups of four male rats were kept on diets containing 0.25, 2.5
or 25% of various edible celluloses for three months. No differences
were observed among the groups with regard to growth and faecal
output. Histopathology of the gastrointestinal tract revealed no
treatment-related abnormalities (Frey et al., 1928).
Three groups of five male rats received 0, 5 or 10%
microcrystalline cellulose in their diets for eight weeks. Growth was
comparable to the controls but the 10% groups showed slightly lower
body weights. Haematology, serum chemistry and vitamin B1 levels in
blood and faeces showed no differences from the controls (Yoshitoshi
Internal Semina, 1966).
Long-term studies
Rat
Three groups of 50 male and 50 female rats received in their diet
for 72 weeks either 30% 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 (Hazelton Laboratories, 1963).
OBSERVATIONS 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 three months. The only effect
noted was an increase in bowel movements but no diarrhoea or other
gastrointestinal disturbances were seen (Frey et al., 1928).
Eight male and eight female volunteers supplemented their normal
diet with 30 g microcrystalline cellulose per day either as dry powder
or gel (15% aqueous) for six weeks followed by two weeks without
supplementation. No adverse findings were reported regarding
acceptance or body weight but most subjects complained of fulness 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 five to
eight times during the test period. Microscopy revealed the presence
of microcrystalline cellulose (Hazelton Laboratories, 1962).
In another study eight healthy males received 30 g micro-
crystalline 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 1131-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 B1 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 a virtually complete absence of digestion or
absorption. 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 considered to be attributable to the
inadequacies of a diet containing a large amount of indigestible
material.
EVALUATION
Estimate of acceptable daily intake for man
Not limited.*
REFERENCES
Baker, E. M. (1966) Unpublished report of F.M.C. Corporation
Baker, E. M. (1968) Unpublished report of F.M.C. Corporation
Frey, J. W., Harding, E. R. & Helmbold, T. R. (1928) Med. J. Rec.,
June, 585
Hazelton Laboratories Inc. (1959) Unpublished report submitted by
American Viscose Corporation
Hazelton Laboratories Inc. (1962) Unpublished report submitted by
American Viscose Corporation
Hazelton Laboratories Inc. (1963) Unpublished report submitted by
American Viscose CorporaTion
Hazelton 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 relevant paragraph in the seventeenth report, pages 10-11.