GLUCOSE ISOMERASE (IMMOBILIZED) FROM STREPTOMYCES OLIVACEUS
EXPLANATION
This enzyme preparation has not previously been evaluated by the
Joint FAO/WHO Expert Committee on Food Additives.
BIOLOGICAL DATA
Biochemical aspects
No information available.
Toxicological studies
Special study on reproduction
Rats
Groups of 10 male and 10 female Charles-River CD rats were fed
diets containing 0, 1.5, 3.0, or 6.0% immobilized glucose isomerase
for 100 days, at which time they were mated on a one-to-one basis.
Groups of 15 males and 15 females (F1 generation) that resulted from
the mating were fed the same diets for 90 days; the animals were then
sacrificed for gross and microscopic pathology studies. No compound-
related effects were reported with respect to fertility indices, body
weights, food consumption, ophthalmoscopy, haematology, clinical
chemistry, urinalysis, or gross or microscopic pathology (Geil
et al., 1975).
Acute toxicity
LD50
Species Material tested Route (mg/kg b.w.) Reference
Rat S. olivaceus oral (gavage) 2500 Hartnagel, 1970
cells
Rat S. olivaceus oral (gavage) 50 Porter &
fermenter beer ml/kg Hartnagel, 1974
Rat non-immobilized oral (gavage) 3330 Hartnagel, 1971
glucose isomerase
Rat immobilized oral (gavage) 3330 Hartnagel, 1971
glucose isomerase
Short-term studies
Rats
Groups of 15 male and 15 female Charles-River CD rats were fed
diets containing 0, 1.5, 3.0, or 6.0% immobilized glucose isomerase
for 90 days. Haematology, clinical chemistry, and urinalysis
measurements were conducted on 5 rats/sex/dose at 90 days, and on 5
male and 5 female control and high-dose animals at 30 and 60 days.
Gross pathology studies were conducted on all animals and microscopic
pathology was conducted on 5 males and 5 females from the high-dose
groups and controls. Total leucocyte counts were elevated in the high-
and mid-dose animals at 90 days. There were no reported compound-
related changes with respect to body-weight gain, food consumption,
ophthalmoscopy, clinical chemistry, urinalysis, organ weights, or
gross or microscopic pathology (Benson et al., 1975).
Dogs
Groups of 4 male and 4 female beagle dogs were fed diets
containing 0, 1.5, 3.0, or 6.0% immobilized glucose isomerase in the
diet for 90 days. One female control dog died during the study; the
likely cause of death was pneumonia. Other dogs on test also developed
acute pneumonia, possibly related to rooting and sniffing in the
powdered diet. The pathology report indicated that acute exudative
(lung) lesions noted in control and all treatment groups likely
resulted from secondary bacterial infection in areas of the lung
previously damaged by lung worms (Cookson et al., 1975).
Because of the lung pathology noted above in the first dog study,
a new study was undertaken. Groups of 4 male and 4 female beagle dogs
were fed diets containing 0, 1.5, 3.0, or 6.0% immobilized glucose
isomerase for 90 days. No compound-related changes occurred with
respect to body-weight gain, food consumption, ophthalmoscopy,
haematology, clinical chemistry, urinalysis, organ weights, or gross
or microscopic pathology. Lung lesions occurred at a high incidence in
all dose groups and the controls and may have been due to infection
with parasitic larvae in the lungs (Harris & Teeter, 1976).
Long-term studies
No information available.
Observation in man
No information available.
Comments
No compound-related adverse effects were reported when dietary
levels of up to 6% of immobilized glucose isomerase were fed to rats
in reproduction and subchronic toxicity studies and to dogs in
subchronic toxicity studies.
EVALUATION
Level causing no toxicological effect
Rat: 6% (60,000 ppm) in the diet, equivalent to 6000 mg/kg b.w./day.
Estimate of Acceptable Daily Intake for Man
Acceptable for use in food processing when used as a component in an
immobilized system.
REFERENCES
Benson, B.W., Geil, R.G., Keller, W.F., & Blanchard, G.L. (1975).
Subchronic studies of the toxicity of glucose isomerase enzyme;
II. Ninety day feeding study in rats. Unpublished study of the
International Research and Development Corporation. Submitted to
the World Health Organization by Miles Laboratories, Inc.
Cookson, K.M., Geil, R.G., & Keller, W.F. (1975). Subchronic studies
of the toxicity of glucose isomerase enzyme: I. Ninety day
feeding study in dogs. Unpublished study of the International
Research and Development Corporation. Submitted to the World
Health Organization by Miles Laboratories, Inc.
Geil, R.G., Benson, B.W., Harris, S.B., & Keller, W.F. (1975).
Subchronic studies of the toxicity of glucose isomerase enzyme:
III. Two generation feeding study in rats. Unpublished study of
the International Research and Development Corporation. Submitted
to the World Health Organization by Miles Laboratories, Inc.
Harris, D.L. & Teeter, C.L. (1976). Subchronic studies of the toxicity
of glucose isomerase enzyme; IV. Ninety day feeding study in
dogs. Unpublished study of the WARF Institute Inc. Submitted to
the World Health Organization by Miles Laboratories, Inc.
Hartnagel, R.E. (1970). The acute oral toxicity of a strain of glucose
isomerase-producing S. olivaceus cells. Unpublished study of
Miles Laboratories, Inc. Submitted to the World Health
Organization by Miles Laboratories, Inc.
Hartnagel, R.E. (1971). The acute oral toxicity of fixed and non-fixed
glucose isomerase and isomerized syrup. Unpublished study of
Miles Laboratories Inc. Submitted to the World Health
Organization by Miles Laboratories, Inc.
Porter, M.C. & Hartnagel, R.E. (1974). Study of the acute oral
toxicity of glucose isomerase fermentor beer in the rat.
Unpublished study of Miles Laboratories, Inc. Submitted to the
World Health Organization by Miles Laboratories, Inc.
See Also:
Toxicological Abbreviations