GLUCOSE ISOMERASE (IMMOBILIZED) FROM BACILLUS COAGULANS
EXPLANATION
This enzyme preparation has not been previously evaluated by the
Joint FAO/WHO Expert Committee on Food Additives.
BIOLOGICAL DATA
Biochemical aspects
No studies available.
Toxicological studies
Special study on mutagenicity
Rats
A dominant lethal study was carried out using Sprague-Dawley
rats. Groups of 12 or 15 males were dosed twice daily for 5
consecutive days by gavage with immobilized glucose isomerase in an
aqueous 0.5% tragacanth gum suspension such that they received a total
daily dose of 0, 3000, or 9000 mg/kg b.w. of the enzyme. A positive
control group of 11 males received 3 mg/kg b.w. of thiotepa per day by
i.p. injection. On the sixth day following treatment, each male was
housed with two females. Every 7 days, 2 new females were paired with
every male, and the procedure continued for a total of 10 weeks. Half
of the females were sacrificed on day 5 of gestation, and the other
half on day 21. A slight reduction in testicular weights was observed
in high-dose males and a significant increase in pre-implantation
losses occurred in low-dose, but not high-dose females in the 10-week
mating. No compound-related effects were observed with respect to
weight gain in males, fertilization index, development of fertilized
ova, or post-implantation loss (Tesh, 1976).
Special study on reproduction
Rats
A 3-generation reproduction study was carried out using groups of
15 male and 30 female Sprague-Dawley rats given 0, 0.5, 1.0, or 5.0%
immobilized glucose isomerase in the diet. These dietary
concentrations were given for 70 days prior to and through mating (on
a 1 male to 2 female basis) and throughout 2 successive pregnancies in
each of 3 generations. The litters arising from the first pregnancy
were sacrificed after 14 days of lactation and the second litter of
each generation stayed with the dam until weaning, when 15 males and
30 females were selected at random to produce the succeeding
generation. After each round of mating had been completed, 5 pregnant
females from each group were sacrificed at day 14 of gestation for
examination of uterine contents. A total of 20 males and 20 females
from the F3b litter were sacrificed after weaning for gross and
microscopic pathological examination. No compound-related effects were
reported on body-weight gain of parental animals of either sex, food
consumption, litter weights, mating performance, reproductive indices,
foetal development, or gross or microscopic pathology. There was an
increased incidence of females with irregular estrous cycles and
increased pre-coital intervals in the mid- and high-dose groups.
However, there was no effect on reproductive performance in these
groups. There was a slight increase in gonadal weights in the mid- and
high-dose F3b males, but no gross or microscopic changes related to
treatment were found (Tesh & Smith, 1976).
Special studies on teratogenicity
Rats
Groups of 20 pregnant female CD rats were fed diets containing 0,
0.5, 1.0, or 5.0% immobilized glucose isomerase in the diet from days
6 through 15 of gestation. The animals were sacrificed on day 21 of
pregnancy; one-third of the foetuses were processed for examination of
soft tissue anomalies and the remaining foetuses were processed for
examination of skeletal abnormalities. There was an increase in pre-
implantation loss in the high-dose group; however, no effect was
reported on the number of viable foetuses, and the pre-implantation
effect seemed to be due to an increase in corpora lutea in the high-
dose rats (Tesh et al., 1975).
Rabbits
Groups of 20 pregnant New Zealand-strain rabbits were dosed by
gavage with 0, 250, 500, or 750 mg/kg b.w. immobilized glucose
isomerase (in an aqueous 0.5% tragacanth-gum vehicle) from days 6
through 18 of pregnancy. The animals were sacrificed on day 29 of
pregnancy. Foetuses were examined internally and externally and then
processed for skeletal examination. No compound-related effects were
observed on maternal weight-gain, pre- or post-implantation loss,
litter size, foetal weight or foetal anomalies (Tesh & Toseland,
1975).
Acute toxicity
LD50
Species Route (mg/kg b.w.) Reference
Mouse oral (gavage) 6,000 Novo, 1974a
Rat oral (gavage) 6,000 Novo, 1974b
Dog oral (gavage) 5,000 Novo, 1975
Short-term studies
Rats
Groups of five female Wistar rats were fed diets containing 0, 1,
or 10% immobilized glucose isomerase for 4 weeks. Weight gain was
slightly greater in the treated animals and feed intake was
significantly higher in males and females in both treatment groups.
Feed conversion efficiency was slightly reduced in dosed females
during the latter half of the study. Haemoglobin concentrations were
lower in treated as compared to control animals; however, this was
attributed to abnormally high values in the control group. No
treatment-related changes were reported with respect to clinical
chemistry, absolute and relative organ weights, or gross and
microscopic pathology (Novo, 1974c).
Groups of 15 male and 15 female Sprague-Dawley rats were given
diets containing 0, 0.5, 1.0, or 5.0% immobilized glucose isomerase
for 13 weeks. No significant compound-related effects were reported
with regard to body-weight gain, feed consumption, haematology, blood
chemistry, urinalysis, opthalmoscopy, absolute or relative organ-
weights, or gross pathology. There was an increase in incidence and
size of focal mineralization in the kidneys of treated females as
opposed to controls. No other compound-related histological changes
were observed.
Another study was performed to investigate the cause of the renal
mineralization. Groups of 15 female Sprague-Dawley rats were fed one
of two different commercial laboratory diets containing 0, 0.1, 1.0,
or 5.0% immobilized glucose isomerase. Body-weight gain, urinalysis,
organ weights, and gross pathology were not significantly affected by
treatment. There was no effect of treatment on animals fed one of the
laboratory diets. In the animals fed the other diet, the incidence of
focal mineralization was greater in the high-dose group than in the
controls, but the other dose groups did not show a treatment-related
effect (Wheldon & Ben-Dyke, 1975).
Dogs
Groups of 3 male and 3 female beagle dogs were fed diets
containing 0, 0.5, 1.0, or 5.0% immobilized glucose isomerase in the
diet for 13 weeks. No compound-related effects were observed with
respect to body-weight gain, ophthalmoscopy, haematology, blood and
urine chemistry, organ weights, or gross or microscopic pathology
(Wheldon & Ben-Dyke, 1975).
Long-term studies
No information available.
Observations in man
No information available.
Comments
The focal mineralization of the kidney of the rat in one study
was restricted to females receiving 5% of the enzyme preparation.
Females fed a different laboratory diet containing 5% of the enzyme
preparation did not exhibit this lesion. No other significant
compound-related effects were observed in either rat study. No adverse
effects were observed in a short-term feeding study in dogs,
teratology studies in rats and rabbits, or reproduction and dominant
lethal studies in rats.
EVALUATION
Level causing no toxicological effect
Rat: 5% (50,000 ppm) in the diet, equivalent to 5000 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
Novo (1974a). Acute oral toxicity of SP113 to mice. Unpublished report
of Novo Industria A/S. Submitted to the World Health Organization
by Novo Industria A/S.
Novo (1974b). Acute oral toxicity of SP113 to rats. Unpublished report
of Novo Industria A/S. Submitted to the World Health Organization
by Novo Industria A/S.
Novo (1974c). Four week oral toxicity study of glucose isomerase
(SP113) in rats. Unpublished report of Novo Industria A/S.
Submitted to the World Health Organization by Novo Industria A/S.
Novo (1975). Acute toxicity of glucose isomerase-SP113 given once
perorally to Beagle dogs. Unpublished report of Novo Industria
A/S. Submitted to the World Health Organization by Novo Industria
A/S.
Tesh, J.M. (1976). SP113: Dominant lethal study in rats. Unpublished
report of Life Science Research. Submitted to the World Health
Organization by Novo Industria A/S.
Tesh, J.M. & Smith, C. (1976). SP113: Multigeneration study in rats.
Unpublished report of Life Science Research. Submitted to the
World Health Organization by Novo Industria A/S.
Tesh, J.M. & Toseland, A.E. (1975). SP113: Effects upon pregnancy in
the rabbit. Unpublished report of Life Science Research.
Submitted to the World Health Organization by Novo Industria A/S.
Tesh, J.M., Toseland, A.E., & Pinson, C.D. (1975). SP113: Effects upon
pregnancy in the rat. Unpublished report of Life Science
Research. Submitted to the World Health Organization by Novo
Industria A/S.
Wheldon, G.H., Ben-Dyke, R., Perry, M.C., & Newman, A.J. (1975).
SP113: Toxicity in continuous dietary administration to rats for
13 weeks. Unpublished report of Life Science Research. Submitted
to the World Health Organization by Novo Industria A/S.
Wheldon, G.H., & Ben-Dyke, R. (1975). SP113: Toxicity in dietary
administration to dogs over 13 weeks. Unpublished report of Life
Science Research. Submitted to the World Health Organization by
Novo Industria A/S.
See Also:
Toxicological Abbreviations