Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
0.176 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):
25
Modified dose descriptor starting point:
NOAEC
Value:
4.41 mg/m³
Explanation for the modification of the dose descriptor starting point:

NAEC worker (8h) = (2.5 mg/kg bw/0.38 m³/kg bw) * 6.7 m³/ 10 m³ [where: NAEC is the modified starting point; 2.5 mg/kg bw is the NOAEL for repeated toxicity, based on the substance purity (Colipa num 15, SCCS/1382/10); 0.38 m³/kg bw is the default respiratory volume for the rat corresponding to the daily duration of human exposure; for workers a further correction is needed for the difference between respiratory rates under standard conditions and under conditions of light activity. This correction factor derives from the inhalation volumes in 8 hours under the respective conditions (6.7 m3 for base level, 10 m3 for light activity)]

AF for dose response relationship:
1
Justification:
data well supported
AF for differences in duration of exposure:
2
Justification:
sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Scaling issues just evaluated in modified starting poi
AF for other interspecies differences:
2.5
Justification:
Remaining differences
AF for intraspecies differences:
5
Justification:
worker factor
AF for the quality of the whole database:
1
Justification:
Good quality and reliability
AF for remaining uncertainties:
1
Justification:
Good quality and reliability
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
Most sensitive endpoint:
acute toxicity
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.025 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
Value:
2.5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Long-term DNEL for dermal route calculation (systemic effects, route to-route extrapolation) = 2.5 mg/kg bw is the NOAEL for repeated dose toxicity oral route / 100 =  0.025 mg/kg bw; AF workers = 4 (rat to human)*5 (workers)*2(subchronic to chronic) * 2.5 = 100

AF for dose response relationship:
1
Justification:
data well supported
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
From rat to humans
AF for other interspecies differences:
2.5
Justification:
Remaining differences
AF for intraspecies differences:
5
Justification:
Worker population
AF for the quality of the whole database:
1
Justification:
Good quality and reliability
AF for remaining uncertainties:
1
Justification:
Good quality and reliability
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information
Explanation for the modification of the dose descriptor starting point:

The substance is not classified for acute toxicity hazards for this reason no acute DNEL(S) need to be calculated

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

The Derived No Effect Levels for inhalation and dermal long-term exposure are estimated from the No Observed Effect Level obtained from the reproductive toxicity assessment.
In general, the calculations of DNELs is based on the observed effect level and have to be corrected for the differences between effect assessment data and the real human exposure situation, taking into account variability and uncertainty within and between species. In order to correct the interspecies difference between rat and human the no observed effect level has to be corrected as mentioned below.  

SYSTEMIC EFFECTS LONG TERM EXPOSURE - INHALATION ROUTE
NAEC worker (8h) = (2.5 mg/kg bw/0.38 m³/kg bw) * 6.7 m³/ 10 m³ [where: NAEC is the modified starting point; 2.5 mg/kg bw is the NOAEL for repeated dose toxicity (oral route); 0.38 m³/kg bw is the default respiratory volume for the rat corresponding to the daily duration of human exposure. For workers a further correction is needed for the difference between respiratory rates under standard conditions and under conditions of light activity. This correction factor derives from the inhalation volumes in 8 hours under the respective conditions (6.7 m³ for base level, 10 m³/kg for light activity)].

Thus, the corrected starting point NAEC was estimated to be 4.41 mg/m³. Subsequently other assessment factors have been used to derived the DNEL:
- differences in duration of exposure 2, because the starting value resulted from a subchronic study
- remaining differences 2.5
- intraspecies differences 5, for worker population

The overall assessment factor (AF) is equal to: 2* 2.5 * 5 = 25  
DNEL is therefore obtained as followed: DNEL = NAEC / AF (overall assessment factor) = 2.5 mg/ m3 / 25 = 0.17 mg/m3  

 

SYSTEMIC EFFECTS LONG TERM EXPOSURE - DERMAL ROUTE
The following assessment factors have been used to derived the DNEL:
- differences in duration of exposure 2, because the starting value resulted from a subchronic study
- for interspecies differences the allometric scaling of 4 has been used because the NOAEL was recorded in a study conducted on rats
- remaining differences 2.5
- intraspecies differences 5, for worker population.

The overall assessment factor (AF) is equal to: 2 * 4* 2.5 * 5 = 100  

DNEL is therefore obtained as followed:  DNEL = NOAEL / AF (overall assessment factor) = 2.5 mg/kg bw/day / 100 = 0.025 mg/kg bw/day

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.043 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
Value:
2.174 mg/m³
Explanation for the modification of the dose descriptor starting point:

NOAEL/1.15 (sRV for 24h rat)

AF for dose response relationship:
1
Justification:
Data well supported
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
Remaining differences
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
Justification:
Good quality and reliability
AF for remaining uncertainties:
1
Justification:
Good quality and reliability
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
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:
0.02 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEL
Value:
4 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

DNEL = 4/ 200 (AF) = 0.02. The most sensitive available end point is the repeated dose toxicity dermal for which DNEL is derived.

AF for dose response relationship:
1
Justification:
data well suported
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
Remaining differences
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
Justification:
Good quality and reliability
AF for remaining uncertainties:
1
Justification:
Good quality and reliability
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.013 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
Value:
2.5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No default factor should be introduced when performing on the same route Long-term DNEL for oral route calculation (systemic effects, route to-route extrapolation) = 2.5 / 4*2.5*10 (b) *2 (c) = 0.125 mg/kg bw/day (b) assessment factors (interspecies * intraspecies (4*2.5) * 10) (c) Correction for duration from subchronic to chronic (6)

AF for dose response relationship:
1
Justification:
Data well supported
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
Remaining differences
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
Justification:
Good quality and reliability
AF for remaining uncertainties:
1
Justification:
Good quality and reliability
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

The Derived No Effect Levels for oral, inhalation and dermal long-term exposure are estimated from the No Observed Effect Level obtained from the repeated dose toxicity assessment.
In general, the calculations of DNELs is based on the observed effect level and have to be corrected for the differences between effect assessment data and the real human exposure situation, taking into account variability and uncertainty within and between species. In order to correct the interspecies difference between rat and human the no observed effect level has to be corrected as mentioned below.  

GENERAL POPULATION: SYSTEMIC EFFECTS LONG TERM EXPOSURE - INHALATION ROUTE
NAEC general population = (NOAEL oral-rat / sRV rat general population)

NOAEL oral – rat = 2.5 mg/kg bw
sRV (standard respiratory volume) general population: rat 24 h exposure (m3/kb bw) = 1.15

Thus, the corrected starting point NAEC was estimated to be 2.17 mg/m³. Subsequently other assessment factors have been used to derived the DNEL:
- differences in duration of exposure 2, because the starting value resulted from a subchronic study
- for interspecies differences the allometric scaling of 4 has been used because the NOAEL was recorded in a study conducted on rats
- remaining differences 2.5
- intraspecies differences 10, for general population

The overall assessment factor (AF) is equal to: 2 * 4 * 2.5 * 10 = 200  
DNEL is therefore obtained as followed: DNEL = NAEC / AF (overall assessment factor) = 0.04348 mg/m3    

GENERAL POPULATION: SYSTEMIC EFFECTS LONG TERM EXPOSURE - DERMAL ROUTE
The following assessment factors have been used to derived the DNEL:
- differences in duration of exposure 2, because the starting value resulted from a subchronic study
- for interspecies differences the allometric scaling of 4 has been used because the NOAEL was recorded in a study conducted on rats
- remaining differences 2.5
- intraspecies differences 10, for general population.

The overall assessment factor (AF) is equal to: 2 * 4* 2.5 * 10 = 200  

DNEL is therefore obtained as followed:  DNEL = NOAEL / AF (overall assessment factor) = 4 mg/kg bw/day / 200 = 0.025 mg/kg bw/day

GENERAL POPULATION: SYSTEMIC EFFECTS LONG TERM EXPOSURE - ORAL ROUTE
The following assessment factors have been used to derived the DNEL:
- differences in duration of exposure 2, because the starting value resulted from a subchronic study
- for interspecies differences the allometric scaling of 4 has been used because the NOAEL was recorded in a study conducted on rats
- remaining differences 2.5
- intraspecies differences 10, for general population.

The overall assessment factor (AF) is equal to: 2 * 4* 2.5 * 10 = 200

DNEL is therefore obtained as followed:  DNEL = NOAEL / AF (overall assessment factor) = 2.5 mg/kg bw/day / 200 = 0.0125 mg/kg bw/day