Xylose

Acute Toxicity: oral

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:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Cross-reference

Reason / purpose for cross-reference:

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

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

GLP compliance:

not specified

Test type:

other: oral feeding

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Xylose

EC Number:

200-400-7

EC Name:

Xylose

Cas Number:

58-86-6

Molecular formula:

C5H10O5

IUPAC Name:

(2S,3R,4S; 5R)-oxane-2,3,4,5-tetrol

Details on test material:

-Purity: >99%

Test animals

Species:

rat

Strain:

Fischer 344/DuCrj

Sex:

male/female

Details on test animals or test system 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 levels

Effect levels 1

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

Effect levels 2

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:

other: 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.

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:

GHS criteria not met

Conclusions:

LD50 > 2200 mg/kg in males; LD50 > 2500 mg/kg in females

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.