Xylose

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

No adverse effects were observed in reproductive organs at >5% (highest dose tested) in a 104-week feeding study in rats. Additionally, D-xylose is administered routinely to humans, including pregnant females, without adverse effect.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Study duration:

chronic

Species:

rat

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

D-xylose, a pentose sugar, is not expected to cause adverse reproductive or developmental effects and additional animal testing is not scientifically justified. In a 2-year rat study, a diet of 5% D-xylose (2214 and 2513 mg/kg/day for males and females, respectively) did not result in adverse effects on reproductive organs (Kuroiwa, 2005). Further, there is a history of the safe use of D-xylose in humans. D-xylose is commonly administered to humans as a diagnostic tool to study intestinal malabsorption. This test typically involves the oral administration of a large dose (approximately 25 g, 400 mg/kg in a 60 kg human) (for example, Worvag, 1987).

In summary, there is no indication that exposure to D-xylose results in adverse effects to reproduction. This is further supported by the fact that D-xylose is administered routinely to humans, including pregnant females, without adverse effect.

Effects on developmental toxicity

Description of key information

No adverse litter effects were observed in rats after administration of D-xylose to pregnant dams. In addition, the use of D-xylose in pregnant human females has also been documented, with no adverse effects noted following administration.

Link to relevant study records

Reference

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Remarks:

This study reported the effect of the test substance on litters of pregnant rats fed the substance for 7 days during gestation. Animals were sacrificed and foetuses were examined for malformations to determine effects. No other data was reported. This study along with human data is used to provide a weight of evidence for the hazard endpoint that is sufficient for the purpose of classification and labelling and/or risk assessment.

Principles of method if other than guideline:

Groups of pregnant rats were fed the test substance for 7 days during gestation. Animals were sacrificed at 21 days gestation and the foetuses were examined for malformations.

GLP compliance:

no

Limit test:

no

Species:

rat

Strain:

Long-Evans

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: Not reported
- Weight at study initiation: 150 - 200g
- Fasting period before study: No
- Housing: Mated in single cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): not reported
- Acclimation period: not reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): not reported
- Humidity (%): not reported
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): not reported

Route of administration:

oral: feed

Vehicle:

not specified

Details on exposure:

DIET PREPARATION: The animals received 4 g of xylose in their diet. No further details were reported.

Analytical verification of doses or concentrations:

not specified

Details on mating procedure:

- M/F ratio per cage: 1 to 1
- Proof of pregnancy: sperm in vaginal smear designated as day 0 of pregnancy

Duration of treatment / exposure:

7 days of gestation

Frequency of treatment:

Daily

Duration of test:

Females were sacrificed on gestation day 21

No. of animals per sex per dose:

not reported

Control animals:

yes, plain diet

Details on study design:

No further details reported.

Maternal examinations:

CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes
- Time schedule for examinations: mother rats were weighed every second day

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No data

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 21
- Organs examined: uteri removed and examined

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No data
- Number of corpora lutea: No data
- Number of implantations: Yes
- Number of early resorptions: No data
- Number of late resorptions: No data
Other:
- Placentas weighted: yes

Fetal examinations:

Foetuses were examined for malformations. Frequently, the skeletons of the foetuses were cleared.

Dose descriptor:

NOAEL

Effect level:

>= 4 other: g in diet

Based on:

test mat.

Basis for effect level:

other: developmental toxicity

Dose descriptor:

NOAEL

Effect level:

>= 4 other: g in diet

Based on:

test mat.

Basis for effect level:

other: No apparent effects were observed on litters at 4 g of xylose in the diet.

Abnormalities:

no effects observed

Developmental effects observed:

no

Conclusions:

The test substance is not uniquely toxic to the developing fetus.
This study and the conclusions which are drawn from it fulfil the quality criteria (validity, reliability, repeatability).

Executive summary:

Groups of pregnant rats were fed 4 grams of test substance in their diet for 7 days. In order to avoid loss by cannibalism of placenta and foetuses, the animals were sacrificed under ether anaesthesia on the 21^st gestation day. The uteri were removed in toto, implantation sites counted, placentas and foetuses weighed and measured. The fetuses were examined for malformations. Frequently the skeletons of the foetuses were cleared. The treatment of groups of pregnant rats with the test substance during the gestation period had no apparent effect on the litter.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Species:

other: rat and humans

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

D-xylose, a pentose sugar, is not expected to cause adverse reproductive or developmental effects and additional animal testing is not scientifically justified. In a rat study, groups of pregnant rats were fed 4 grams of test substance in their diet for 7 days (Thiersch, 1971). Following removal of the uteri, implantation sites were counted, and placentas and foetuses weighed and measured. The foetuses were examined for malformations. Several of the foetal skeletons were cleared. The treatment of groups of pregnant rats with the test substance during the gestation period had no apparent effect on the litter. Further, there is a history of the safe use of D-xylose in humans. D-xylose is commonly administered to humans as a diagnostic tool to study intestinal malabsorption. This test typically involves the oral administration of a large dose (approximately 25 g, 400 mg/kg in a 60 kg human) (for example, Worvag, 1987). The use of D-xylose in pregnant human females has also been documented (Egwuatu, 1981; Hofmann, 2001). In the first study, 16 pregnant females in the second and third trimesters of their first pregnancy and 18 non-pregnant females were given an oral bolus of 5 grams of D-xylose. In the second study, 53 pregnant women in labour were given an intravenous infusion of 5% D-xylose. Glucose, insulin, and bilirubin were measured in both maternal and foetal blood; no adverse effects were noted following xylose administration.

In summary, there is no indication that exposure to D-xylose results in adverse effects to reproduction and development. This is further supported by the fact that D-xylose is administered routinely to humans, including pregnant females, without adverse effect.

Toxicity to reproduction: other studies

Description of key information

No adverse effects were observed in reproductive organs at >5% (highest dose tested) in a 104-week feeding study in rats. Additionally,D-xylose is administered routinely to humans, including pregnant females, without adverse effect.

Link to relevant study records

Reference

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:

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

Reason / purpose for cross-reference:

reference to same study

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:

not specified

Type of method:

in vivo

Species:

rat

Strain:

Fischer 344/DuCrj

Sex:

male/female

Details on test animals or test system and environmental conditions:

For additional details refer to Section 7.5.1: DL.K2.104Wk.Feed.RD/CARC.R.Pub.KD

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

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

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

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.

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

Conclusions:

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

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.

Justification for classification or non-classification

The test substance was not uniquely toxic to the developing foetus and no effects were observed in reproductive organs in a 104-week dietary study, therefore no classification is required for developmental or reproductive toxicity according to EU Directive 67/548/EEC and EU Classification and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.