Registration Dossier

Administrative data

Endpoint:
in vivo mammalian somatic and germ cell study: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Lack of carcinogenicity of D-xylose given in the diet to F344 rats for two years
Author:
Kuroiwa Y, Nishikaw A, Imazawa T, Kitamura Y, Kanki K , Umemura T, Hirose M
Year:
2005
Bibliographic source:
Food Chem Toxicol., 43(9):1399-1404

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: Ministry of Health, Labor and Welfare of Japan), 1996b. Guidelines for Designation of Food Additives, and for Revision of Standard for Use of Food Additives, Article No. 29 of the Life and Sanitation Bureau.
Deviations:
no
GLP compliance:
no
Type of assay:
other: carcinogenicity study

Test material

Constituent 1
Chemical structure
Reference substance name:
Xylose
EC Number:
200-400-7
EC Name:
Xylose
Cas Number:
58-86-6
Molecular formula:
C5H10O5
IUPAC Name:
xylose
Details on test material:
- Purity: > 99%

Test animals

Species:
rat
Strain:
Fischer 344/DuCrj
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Vehicle:
Unchanged (no vehicle)
Duration of treatment / exposure:
104 weeks
Frequency of treatment:
Daily
Doses / concentrationsopen allclose all
Dose / conc.:
2.5 other: %
Remarks:
equivalent to 1033 and 1203 mg/kg/day in males and females, respectively
Dose / conc.:
5 other: %
Remarks:
equivalent to 2214 and 2513 mg/kg/day in males and females, respectively
No. of animals per sex per dose:
50/sex/dose
Control animals:
yes, plain diet

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Remarks on result:
other: No tumours were observed in this carcinogenicity assay, therefore the test substance is not a genotoxic mutagen or a carcinogen.
Additional information on results:
It was concluded that, under the present experimental conditions, D-xylose is not carcinogenic to F344 rats.

Applicant's summary and conclusion

Conclusions:
No tumours were observed in this carcinogenicity assay, therefore the test substance is not a genotoxic mutagen or a carcinogen.
Executive summary:

Dietary administration of the test substance to F344 rats at dose levels of 2.5% or 5% (equivalent to overall achieved intakes of 1033 or 2214 mg/kg/day for males and 1203 or 2513 mg/kg/day for females,

respectively) in the diet for 104 weeks exerted no effects on mortality, clinical signs or haematology data, except soft faeces in 5% males and females. Although decreases in the final body weights were recorded

in males and females receiving the 5% dose, the values during the experimental period were less than 10% lowered as compared with the control group. This weight suppression might be a result from the low

calorific property of the test substance. However, the effect of the test substance on total calorie intake was considered to be a little, because the quantity of the test substance in the admixture was only 5% at the maximum, and food consumptions seem to have increased with the test substance concentrations in order to compensate low calorie. Soft faeces observed in 5% males and females, possibly caused by the high concentration of the test substance excretion in the faeces, might be concerned in body weight suppression. In the organ weights, decrease in absolute and increase in relative brain weights were observed in males of the 5% group, and decrease of absolute kidney values was noted in females of the 5% group. However, here were no remarkable changes in these organs on histopathology. Increases in the absolute and relative testis weights were observed in males of the 5% group. In rats, spontaneous interstitial cell tumours in the testes occur at very high incidence, reaching 81–91% at 104 weeks of age. In the present study, the incidence of interstitial cell tumours in the control group was 92% (within the reference background range), whereas that in the 5% group was decreased to 72%. This low incidence was considered to reflect differences in testis weights between the control and 5% groups. Dietary restriction has been shown to reduce the incidences of a variety of rodent spontaneous tumours, including interstitial cell tumours in F344 rats. Additionally, the suppression of body weight is considered to be associated with low neoplasm incidences. In the present study, the suppression of body weight may have caused a low incidence of testis interstitial cell tumour. However, suppression of body weight gain is much weaker than those in dietary restriction experiments. Therefore, it is likely that unknown factors other than lower body weight might be also concerned. Histopathological assessment revealed pituitary adenomas and endometrial stromal polyps in the females, and thyroid adenomas in both sexes at relatively high incidences. However, the lack of significant differences between the control and treated groups suggests a spontaneous nature for these lesions. Large granular leukaemia is well known to arise in aged F344 rats, and the incidence observed in our control group was within the range of reported values. The test substance-treated groups showed a tendency for decrease in the incidence of large granular leukaemia, and again this might have been due to dietary restriction. Incidence in large granular leukaemia might also be due to low body weight. Tumours were also detected in other organs or tissues, but their incidences were consistently very low. None of the treated groups showed significant increase in the incidence of any specific tumour over the control group level. In conclusion, the present results demonstrate that the test substance dose not exert any carcinogenic potential in male and female F344 rats fed for two years.