Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
86.96 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEC
DNEL value:
17 391 mg/m³
Explanation for the modification of the dose descriptor starting point:
NOAEL of 20000 mg/kg/day. A modification of starting point for rat respiratory volume (0.38 m3/kg bw) was applied per REACH guidance R.8.4.2. A modification (6.7 m3 / 10 m3) was applied to account for the increased respiratory volumes in active workers as compared to individuals at rest per REACH guidance R.8.4.2. 20000 mg/kg/day / 0.38 m3/kg = 52631 * [6.7 m3 / 10 m3] = 35262 mg/ m3
AF for dose response relationship:
1
Justification:
The dose descriptor is the NOAEL in a repeat dose toxicity study, the highest dose tested. An assessment factor of 1 is appropriate per REACH guidance R.8.4.3.1.
AF for differences in duration of exposure:
2
Justification:
Based on the fact that the data was from a subchronic study, an assessment factor of 2 is appropriate per REACH guidance R.8.4.3.1.
AF for interspecies differences (allometric scaling):
4
Justification:
Available study data was conducted in rats. A factor of 4 is appropriate per REACH guidance R.8.4.3.1.
AF for other interspecies differences:
2.5
Justification:
A default factor of 2.5 is appropriate per REACH guidance R.8.4.3.1.
AF for intraspecies differences:
5
Justification:
Since there are no data to justify a reduction or increase in the intraspecies default assessment factor, a default factor of 5 is appropriate per REACH guidance R.8.4.3.1.
AF for the quality of the whole database:
1
Justification:
A high quality, robust toxicity database exists for this substance. An assessment factor of 1 is appropriate per REACH guidance R.8.4.3.1.
AF for remaining uncertainties:
2
Justification:
Oral to inhalation extrapolation. A factor of 2 is appropriate per REACH guidance R.8.4.3.1.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
200 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
DNEL value:
20 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The NOAEL in a 13-week study in rats was 20000 mg/kg, the highest dose tested.
AF for dose response relationship:
1
Justification:
The dose descriptor is the NOAEL in a repeat dose toxicity study, the highest dose tested. An assessment factor of 1 is appropriate per REACH guidance R.8.4.3.1.
AF for differences in duration of exposure:
2
Justification:
Based on the fact that the data was from a subchronic study, an assessment factor of 2 is appropriate per REACH guidance R.8.4.3.1.
AF for interspecies differences (allometric scaling):
4
Justification:
Available study data was conducted in rats. A factor of 4 is appropriate per REACH guidance R.8.4.3.1.
AF for other interspecies differences:
2.5
Justification:
A default factor of 2.5 is appropriate per REACH guidance R.8.4.3.1.
AF for intraspecies differences:
5
Justification:
Since there are no data to justify a reduction or increase in the intraspecies default assessment factor, a default factor of 5 is appropriate per REACH guidance R.8.4.3.1.
AF for the quality of the whole database:
1
Justification:
A high quality, robust toxicity database exists for this substance. An assessment factor of 1 is appropriate per REACH guidance R.8.4.3.1.
AF for remaining uncertainties:
1
Justification:
Oral to dermal extrapolation. A factor of 1 is appropriate per REACH guidance R.8.4.3.1.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

In a short-term (13 weeks) study four groups of eight female and eight male Charles River CD rats weighing 120-150 g, were fed 0, 5, 10 and 20 g dietary xylitol/kg/day. Food and water consumption were recorded daily and body weight weekly. Haematology, blood glucose and urinalyses of five male and five female rats of each group were carried out at four, eight and 12 weeks. Alk. Pase, GOT, bilirubin and uric acid in serum and BUN of five males and five females per group were determined at 13 weeks. The animals, particularly the male rats, showed reduced body weight gain and food consumption, that were dose dependent. In the 20% xylitol group BUN was elevated. In treatment groups dose-related decrease of the absolute heart weight are observed. Except for transient diarrhoea in a number of treated animal no other significant changes were observed. No histopathological lesions related to xylitol administered were noticed.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
43.5 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
400
Modified dose descriptor starting point:
NOAEC
DNEL value:
17 391 mg/m³
Explanation for the modification of the dose descriptor starting point:
NOAEL of 20000 mg/kg/day. A modification of starting point for rat respiratory volume (1.15 m3/kg bw) was applied per REACH guidance R.8.4.2. 20000 mg/kg/day / 1.15 m3/kg = 17391 mg/ m3
AF for dose response relationship:
1
Justification:
The dose descriptor is the NOAEL in a repeat dose toxicity study, the highest dose tested. An assessment factor of 1 is appropriate per REACH guidance R.8.4.3.1.
AF for differences in duration of exposure:
2
Justification:
Based on the fact that the data was from a subchronic study, an assessment factor of 2 is appropriate per REACH guidance R.8.4.3.1.
AF for interspecies differences (allometric scaling):
4
Justification:
Available study data was conducted in rats. A factor of 4 is appropriate per REACH guidance R.8.4.3.1.
AF for other interspecies differences:
2.5
Justification:
A default factor of 2.5 is appropriate per REACH guidance R.8.4.3.1.
AF for intraspecies differences:
10
Justification:
Since there are no data to justify a reduction or increase in the intraspecies default assessment factor, a default factor of 10 is appropriate per REACh guidance R.8.4.3.1.
AF for the quality of the whole database:
1
Justification:
A high quality, robust toxicity database exists for this substance. An assessment factor of 1 is appropriate per REACH guidance R.8.4.3.1.
AF for remaining uncertainties:
2
Justification:
Oral to inhalation extrapolation. A factor of 2 is appropriate per REACH guidance R.8.4.3.1.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
100 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEL
DNEL value:
20 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The NOAEL in a 13-week study in rats was 20000 mg/kg, the highest dose tested.
AF for dose response relationship:
1
Justification:
The dose descriptor is the NOAEL in a repeat dose toxicity study, the highest dose tested. An assessment factor of 1 is appropriate per REACH guidance R.8.4.3.1.
AF for differences in duration of exposure:
2
Justification:
Based on the fact that the data was from a subchronic study, an assessment factor of 2 is appropriate per REACH guidance R.8.4.3.1.
AF for interspecies differences (allometric scaling):
4
Justification:
Available study data was conducted in rats. A factor of 4 is appropriate per REACH guidance R.8.4.3.1.
AF for other interspecies differences:
2.5
Justification:
A default factor of 2.5 is appropriate per REACH guidance R.8.4.3.1.
AF for intraspecies differences:
10
Justification:
Since there are no data to justify a reduction or increase in the intraspecies default assessment factor, a default factor of 10 is appropriate per REACh guidance R.8.4.3.1.
AF for the quality of the whole database:
1
Justification:
A high quality, robust toxicity database exists for this substance. An assessment factor of 1 is appropriate per REACH guidance R.8.4.3.1.
AF for remaining uncertainties:
1
Justification:
Oral to dermal extrapolation. A factor of 1 is appropriate per REACH guidance R.8.4.3.1.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
100 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEL
DNEL value:
20 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The NOAEL in a 13-week study in rats was 20000 mg/kg, the highest dose tested.
AF for dose response relationship:
1
Justification:
The dose descriptor is the NOAEL in a repeat dose toxicity study, the highest dose tested. An assessment factor of 1 is appropriate per REACH guidance R.8.4.3.1.
AF for differences in duration of exposure:
2
Justification:
Based on the fact that the data was from a subchronic study, an assessment factor of 2 is appropriate per REACH guidance R.8.4.3.1.
AF for interspecies differences (allometric scaling):
4
Justification:
Available study data was conducted in rats. A factor of 4 is appropriate per REACH guidance R.8.4.3.1.
AF for other interspecies differences:
2.5
Justification:
A default factor of 2.5 is appropriate per REACH guidance R.8.4.3.1.
AF for intraspecies differences:
10
Justification:
Since there are no data to justify a reduction or increase in the intraspecies default assessment factor, a default factor of 10 is appropriate per REACh guidance R.8.4.3.1.
AF for the quality of the whole database:
1
Justification:
A high quality, robust toxicity database exists for this substance. An assessment factor of 1 is appropriate per REACH guidance R.8.4.3.1.
AF for remaining uncertainties:
1
Justification:
The study was conducted according to the oral route. A factor of 1 is appropriate per REACH guidance R.8.4.3.1.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

In a short-term (13 weeks) study four groups of eight female and eight male Charles River CD rats weighing 120-150 g, were fed 0, 5, 10 and 20 g dietary xylitol/kg/day. Food and water consumption were recorded daily and body weight weekly. Haematology, blood glucose and urinalyses of five male and five female rats of each group were carried out at four, eight and 12 weeks. Alk. Pase, GOT, bilirubin and uric acid in serum and BUN of five males and five females per group were determined at 13 weeks. The animals, particularly the male rats, showed reduced body weight gain and food consumption, that were dose dependent. In the 20% xylitol group BUN was elevated. In treatment groups dose-related decrease of the absolute heart weight are observed. Except for transient diarrhoea in a number of treated animal no other significant changes were observed. No histopathological lesions related to xylitol administered were noticed.