Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
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: MHLW (Ministry of Health, Labor and Welfare of Japan), 1996: 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
Test type:
other: oral feeding
Limit test:
no

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:
TEST ANIMALS
- Source: Charles River Japan Inc.
- Age at study initiation: 6-week-old
- Fasting period before study: no
- Housing: plastic cages with woodchip bedding (three or four male rats/cage, five female rats/cage)
- Diet (e.g. ad libitum): basal diet (CRF-1) ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24 ± 1°C
- Humidity (%): 55 ± 5%
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12-h light/dark cycle

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
DIET PREPARATION: Diets were prepared once every three months by the forage supplier and preserved in the dark at 4°C prior to use.

Doses:
Nominal: 2.5% and 5% in diet
Actual Ingested (Male): 1033 mg/kg/day and 2214 mg/kg/day
Actual Ingested (Female) 1203 mg/kg/day, and 2513 mg/kg/day
No. of animals per sex per dose:
50/sex/dose
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 104 weeks
- Frequency of observations and weighing: All rats were observed daily for clinical signs and deaths. Body weights were measured once a week for the first five weeks of the study and then once every five weeks.
- Necropsy of survivors performed: yes
- Other examinations performed: organ weights, histopathology, haematology
Statistics:
Data for body weights were analyzed by the Students t-test. Haematology, organ weight and final body weight data were analyzed for homogeneity of variance using the Bartletts test. Where the samples proved to be homogeneous, one-way analysis of variance was employed. If significant heterogeneity of variance (P < 0.01) was apparent, the equivalent non-parametric statistical method of Kruskal–Wallis was used. Where significant differences between the groups were detected, a multiple comparison test (Dunnetts test or Scheffes method) was applied. Final survival rates and the incidences of tumours were compared with the Fishers exact probability test.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 200 mg/kg bw
Based on:
test mat.
Remarks on result:
other: calculated from test material in diet fed over 104 weeks
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 500 mg/kg bw
Based on:
test mat.
Remarks on result:
other: calculated from test material in diet fed over 104 weeks
Mortality:
No significant differences in final survival rate and mean survival time were observed among the groups.
Clinical signs:
No treatment-related clinical signs were noted during the treatment period, except that growth supression and soft faeces in the 5% males and females were found throughout the experimental period.
Body weight:
For details on body weights refer to Sec 7.5.1: DL.K2.104Wk.Feed.RD/CARC.Pub.KD
Gross pathology:
For details on gross pathology refer to Sec 7.5.1: DL.K2.104Wk.Feed.RD/CARC.Pub.KD
Other findings:
For additional details refer to Sec 7.5.1: DL.K2.104Wk.Feed.RD/CARC.Pub.KD

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
LD50 > 2200 mg/kg in males; LD50 > 2500 mg/kg in females
This study and the conclusions which are drawn from it fulfil the quality criteria (validity, reliability, repeatability).
Executive summary:

The two year carcinogenicity of the test substance was examined in groups of 50 male and 50 female F344 rats at dietary doses of 0% (control), 2.5% and 5%. Growth suppression and soft faeces were observed in male and female rats of the 5% group. However, no significant differences from the controls were noted with regard to clinical signs, mortality and haematological findings. 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. The LD50 was calculated from the 104-week study to be >2200 mg/kg in males and >2500 mg/kg in female rats.