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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6.03 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor starting point:
NOAEC
Value:
300 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
150.75 mg/m³
Explanation for the modification of the dose descriptor starting point:

Modification of the starting point (NOAEC of 300 mg/m3):

- Correction of exposure duration in study (6 hrs/day, 5 days/week) to default worker exposure (8 hrs/day, 5 days/week);

- Correction for activity driven differences of respiratory volumes in workers compared to workers in rest (6.7 m3/10 m3).

AF for dose response relationship:
1
Justification:
Not required, starting point is NOAEC
AF for differences in duration of exposure:
2
Justification:
Extrapolation from sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
not for concentration
AF for other interspecies differences:
2.5
Justification:
default factor for remaining differences
AF for intraspecies differences:
5
Justification:
default factor for workers
AF for the quality of the whole database:
1
Justification:
not applicable
AF for remaining uncertainties:
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:
1.5 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
Dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No route to route extrapolation applied. Since no substance specific absorption data is available, default values will be used: 100% for oral and 100% for dermal absorption.

AF for dose response relationship:
1
Justification:
Not required, starting point is NOAEC
AF for differences in duration of exposure:
2
Justification:
Extrapolation from sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Assessment factor for allometric scaling
AF for other interspecies differences:
2.5
Justification:
Default factor for remaining differences
AF for intraspecies differences:
5
Justification:
default factor for workers
AF for the quality of the whole database:
1
Justification:
not applicable
AF for remaining uncertainties:
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:
medium hazard (no threshold derived)

Additional information - workers

Worker DNELs

 

Long-term inhalation

Long-term – inhalation, local/systemic effects (based on the 90 days inhalation study in rats)

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEC: 300 mg/m3

Exposure of rats at concentrations of 300 mg/m3 did not induce changes indicative of local or systemic toxicity (changes in haematology, clinical chemistry and organ weights). Therefore, 300 mg/m3 was considered to be the NOAEC for local and systemic toxicity in rats exposed for 6 hours/day, 5 days/week for a period of 90 days.

Step 2) Modification of starting point

6/8

 

 

 

 

6.7 m3/10 m3

Correction of exposure duration in study (6 hrs/day, 5 days/week) to default worker exposure (8 hrs/day, 5 days/week);

 

Correction for activity driven differences of respiratory volumes in workers compared to workers in rest (6.7 m3/10 m3).

Modified dose-descriptor

300 x 6.7 x 6 / (10 x 8) = 150.75 mg/m3

Step 3) Assessment factors

 

 

Interspecies

2.5

No factor for allometric scaling is needed in case of inhalation exposure. A default factor of 2.5 for remaining uncertainties is used.

Intraspecies

5

Default assessment factor

Exposure duration

2

Extrapolation from sub-chronic to chronic exposure.

Dose response

1

 

Quality of database

1

DNEL

Value

 

150.75 / (2.5 x 5 x 2 x 1 x 1) = 6.0 mg/m3

Long-term dermal

Long-term – dermal, systemic effects (based on the extended one-generation toxicity study in rats) 

As dermal repeated dose toxicity studies with Polyol IXOL B350 are not available, route to route extrapolation was applied to derive a DNEL for the dermal route, based on the systemic NOAEL of 150 mg/kg bw/day from the oral EOGRTS study.

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 150 mg/kg bw/day

 Oral exposure to Polyol IXOL B350 (OECD 443, GLP) at dosages of 0, 75, 150 and 450 mg/kg bw/day resulted in treatment-related adverse findings consisting of intratubular hemorrhage in the kidneys of F0 males administered 450 mg/kg/day and thyroid adenomas in F0 males adminstered>75 mg/kg/day, one female adminstered 450 mg/kg/day, and one F1 male administered 75 mg/kg/day. It should be noted that the relevance of such thyroid effects in rat studies - in quantitative terms - to humans is limited. Therefore the kidney effect is considered the most critical effect of Polyol IXOL B350 after repeated oral exposure. Based on the available study, the overall NOAEL for systemic effects by oral route is 150 mg/kg bw/day.

Step 2) Modification of starting point

1

 

As no substance specific data is available, default figures will be used:Conservative default for route to route: 100% for inhalation and 100% for dermal absorption

Modified dose-descriptor

150 mg/kg bw/day

Step 3) Assessment factors

 

 

Interspecies

4 x 2.5

Assessment factor for allometric scaling and remaining uncertainties.

Intraspecies

5

Default assessment factor

Exposure duration

2

Extrapolation from sub-chronic to chronic exposure

Dose response

1

 

Quality of database

1

 

DNEL

Value

 

150 / (4 x 2.5 x 5 x 2 x 1 x 1) = 1.5 mg/kg bw/day

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.07 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Dose descriptor starting point:
NOAEC
Value:
300 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
53.6 mg/m³
Explanation for the modification of the dose descriptor starting point:

Modification of the starting point (NOAEC of 300 mg/m3):

- Correction of exposure duration in study (6 hrs/day, 5 days/week) to default exposure duration for general population (24 hrs/day, 7 days/week)

AF for dose response relationship:
1
Justification:
Not required, starting point is NOAEC
AF for differences in duration of exposure:
2
Justification:
Extrapolation from sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
not for concentration
AF for other interspecies differences:
2.5
Justification:
default factor for remaining differences
AF for intraspecies differences:
10
Justification:
default factor for general population
AF for the quality of the whole database:
1
Justification:
Not applicable
AF for remaining uncertainties:
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:
no hazard identified
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:
0.75 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
Dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No route to route extrapolation applied.

AF for dose response relationship:
1
Justification:
Not required, starting point is NOAEL
AF for differences in duration of exposure:
2
Justification:
Extrapolation from sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Assessment factor for allometric scaling
AF for other interspecies differences:
2.5
Justification:
Assessment factor for remaining differences
AF for intraspecies differences:
10
Justification:
Default assessment factor for general population
AF for the quality of the whole database:
1
Justification:
Not applicable
AF for remaining uncertainties:
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:
medium hazard (no threshold derived)

Additional information - General Population

General population DNELs

 

Long-term inhalation

Long-term – inhalation, local/systemic effects (based on the 90 days inhalation study in rats) 

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEC: 300 mg/m3

Exposure of rats at concentrations of 300 mg/m3 did not induce changes indicative of local or systemic toxicity (changes in haematology, clinical chemistry and organ weights), Therefore, 300 mg/m3 was considered to be the NOAEC for systemic toxicity in rats exposed for 6 hours/day, 5 days/week for a period of 90 days.

Step 2) Modification of starting point

6/24 x 5/7

 

Correction of exposure duration in study

6 hrs/day, 5 days/week) to default exposure duration for general population (24 hrs/day, 7 days/week)

Modified dose-descriptor

300 x 6 / 24 x 5/7 = 53.6 mg/m3

Step 3) Assessment factors

 

 

Interspecies

2.5

No factor for allometric scaling is needed in case of inhalation exposure. A default factor of 2.5 for remaining uncertainties is used.

Intraspecies

10

Default assessment factor

Exposure duration

2

Extrapolation from sub-chronic to chronic exposure

Dose response

1

 

Quality of whole database

1

DNEL

Value

 

53.6 / (2.5 x 10 x 2 x 1x 1) = 1.07 mg/m3

Long-term oral

Long-term – oral, systemic effects (based the oral EOGRTS study in rats).

No route-to-route extrapolation was applied since the DNEL has been derived from a NOAEL observed in an oral EOGRTS study.

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEC: 150 mg/kg bw/day

Oral exposure to Polyol IXOL B350 (OECD 443, GLP) at dosages of 0, 75, 150 and 450 mg/kg bw/day resulted in treatment-related adverse findings consisting of intratubular hemorrhage in the kidneys of F0 males administered 450 mg/kg/day and thyroid adenomas in F0 males adminstered>75 mg/kg/day, one female adminstered 450 mg/kg/day, and one F1 male administered 75 mg/kg/day. It should be noted that the relevance of such thyroid effects in rat studies - inquantitative terms - to humans is limited. Therefore the kidney effect is considered the most critical effect of Polyol IXOL B350 after repeated oral exposure. Based on the available study, the overall NOAEL for systemic effects by oral route is 150 mg/kg bw/day.

Step 2) Modification of starting point

1

 

Not applicable

Modified dose-descriptor

150 mg/kg bw/day

Step 3) Assessment factors

 

 

Interspecies

4 x 2.5

Assessment factor for allometric scaling and remaining uncertainties.

Intraspecies

10

Default assessment factor

Exposure duration

2  

Extrapolation form sub-chronic to chronic exposure

Dose response

1

 

Quality of database

1

DNEL

Value

 

150 / (4 x 2.5 x 10 x 2 x 1 x 1) = 0.75 mg/kg bw/day