Registration Dossier

Administrative data

Endpoint:
toxicity to reproduction: other studies
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study was selected as the key study because the information provided for the hazard endpoint is sufficient for the purpose of classification and labelling and/or risk assessment.
Cross-reference
Reason / purpose:
reference to same study

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:
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
Remarks:
The study was conducted according to the guideline in effect at the time of study conduct.
GLP compliance:
not specified
Type of method:
in vivo

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Purity: >99%

Test animals

Species:
rat
Strain:
Fischer 344/DuCrj
Sex:
male/female
Details on test animals and environmental conditions:
For additional details refer to Section 7.5.1: DL.K2.104Wk.Feed.RD/CARC.R.Pub.KD

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Details on exposure:
For additional details refer to Section 7.5.1: DL.K2.104Wk.Feed.RD/CARC.R.Pub.KD
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
104 Weeks
Frequency of treatment:
Daily
Duration of test:
104 Weeks
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
2.5 and 5%
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
Males: 1033 mg/kg/day; Females: 1203 mg/kg/day (for the 2.5% nominal dose)
Basis:
actual ingested
Remarks:
Doses / Concentrations:
2214 mg/kg/day; Females: 2513 mg/kg/day (for the 5% nominal dose)
Basis:
actual ingested
No. of animals per sex per dose:
50/sex/dose
Control animals:
yes, plain diet
Details on study design:
For additional details refer to Section 7.5.1: DL.K2.104Wk.Feed.RD/CARC.R.Pub.KD
Statistics:
For additional details refer to Section 7.5.1: DL.K2.104Wk.Feed.RD/CARC.R.Pub.KD

Results and discussion

Effect levels

Dose descriptor:
NOAEL
Effect level:
> 5 other: % nominal (2214 and 2513 mg/kg/day for males and females, respectively)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No adverse effects were observed on reproductive organs at the highest dose tested.

Observed effects

No test substance-related effects were observed on male and female reproductive organs at the highest dose tested. For additional details on systemic toxicity or tumour incidence refer to Section 7.5.1: DL.K2.104Wk.Feed.RD/CARC.R.Pub.KD

Applicant's summary and conclusion

Conclusions:
No test substance related effects were observed on male and female reproductive organs at 5% in diet (the highest dose tested).

The study and the conclusions which are drawn from it fulfil the quality criteria (validity, reliability, repeatability).
Executive summary:

The test substance was administered 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. No effects on mortality, clinical signs or haematology data, except soft feces in 5% males and females were observed. 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. 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. No test substance related-effects were observed in male or female reproductive organs at histopathologic examination.