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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
23.4 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):
75
Dose descriptor starting point:
NOAEL
Value:
996 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
1 756 mg/m³
Explanation for the modification of the dose descriptor starting point:

No data available on inhalation route; therefore DNEL should be derived from an oral route study.

AF for dose response relationship:
1
Justification:
Starting point = NOAEL
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route.
AF for other interspecies differences:
2.5
Justification:
Default factor
AF for intraspecies differences:
5
Justification:
Workers
AF for the quality of the whole database:
1
Justification:
The database is considered relevant to assessment of repeated dose oral toxicity and is considered adequate, robust and reliable.
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:
3.32 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):
300
Dose descriptor starting point:
NOAEL
Value:
996 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
996 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No data available on dermal route; therefore DNEL should be derived from an oral route study.

Default dermal absorption value of 100%

AF for dose response relationship:
1
Justification:
Starting point = NOAEL
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Rat
AF for other interspecies differences:
2.5
Justification:
Default factor
AF for intraspecies differences:
5
Justification:
Workers
AF for the quality of the whole database:
1
Justification:
The database is considered relevant to assessment of repeated dose oral toxicity and is considered adequate, robust and reliable.
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:
no hazard identified

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.77 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):
150
Dose descriptor starting point:
NOAEL
Value:
996 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
866 mg/m³
Explanation for the modification of the dose descriptor starting point:

See discusion.

AF for dose response relationship:
1
Justification:
Starting point = NOAEL
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route
AF for other interspecies differences:
2.5
Justification:
Default factor
AF for intraspecies differences:
10
Justification:
General population
AF for the quality of the whole database:
1
Justification:
The database is considered relevant to assessment of repeated dose oral toxicity and is considered adequate, robust and reliable.
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:
DNEL (Derived No Effect Level)
Value:
1.66 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):
600
Dose descriptor starting point:
NOAEL
Value:
996 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
996 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No data available on dermal route; therefore DNEL should be derived from an oral route study.

Default dermal absorption value of 100%

AF for dose response relationship:
1
Justification:
Starting point= NOAEL
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Rat
AF for other interspecies differences:
2.5
Justification:
Default factor
AF for intraspecies differences:
10
Justification:
General population
AF for the quality of the whole database:
1
Justification:
The database is considered relevant to assessment of repeated dose oral toxicity and is considered adequate, robust and reliable.
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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.66 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):
600
Dose descriptor starting point:
NOAEL
Value:
996 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
996 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Starting point= NOAEL
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Rat
AF for other interspecies differences:
2.5
Justification:
Default factor
AF for intraspecies differences:
10
Justification:
General population
AF for the quality of the whole database:
1
Justification:
The database is considered relevant to assessment of repeated dose oral toxicity and is considered adequate, robust and reliable.
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:
no hazard identified

Additional information - General Population

A.- ACUTE TOXICITY. Systemic effects

Oral exposure

Since the substance is not classified for oral acute exposure, no DNEL for acute systemic effects is to be derived.

Dermal exposure. Systemic effects

 

Since the substance is not classified for dermal acute exposure, no DNEL for acute systemic effects is to be derived.

 

Inhalatory exposure

Since the substance is not classified for inhalation acute exposure, no DNEL for acute systemic effects is to be derived.

 

B.- IRRITATION/ CORROSION

The substance is not irritating or corrosive.

 

C.- SENSITIZATION

The substance does not exhibited experimental evidence of sensitizing potential.

 

D.- MUTAGENICITY/ CARCINOGENICITY

There were no indications of a possible non-threshold mutagenic or tumorigenic response by any exposure route and the experimental results show no positive responses for in vitro mutagenicity assays. Therefore DNELs have not been established either for carcinogenicity nor mutagenicity.

E.- REPEAT DOSE TOXICITY:Systemic effects

Duration differences (the assessment factor for extrapolation from subacute to chronic exposure) is set in the REACH guidance as AF = 6. It is applied in this case because the dose descriptor is derived from a sub-chronic exposure study and the DNEL is for long term exposure.

 

Dose-response related issues

Since the DNEL is to be derived from a starting position based on an NOAEL from a good quality study, the dose response assessment factor was the default value, AF = 1.

 

Quality of whole database

The default assessment factor to be applied is AF = 1. Higher factors may be applied based on scientific judgement related to adequacy and consistency. The database is considered relevant to assessment of repeated dose oral toxicity and is considered adequate, robust and reliable.

 

Dermal exposure

Since no dose descriptor was available from a repeated application dermal toxicity study and dermal exposure is the most probable route of human exposure, it was necessary to derive a corrected dermal NOAEL from the oral NOAEL. The oral dose descriptor was used as the basis for route-to-route extrapolation.

Dermal risk assessment is based on the oral NOAEL of 996 mg/kg/day from the 28 -day rat study.

 

Taking into account a default dermal absorption value of 100% the NOAEL of 996 mg/kg/day is used as the starting point for the dermal route.

 

The following adjustment factors are applied for the identification of the reference MOS:

(1) for duration adjustment a factor of 6 is used;

(2) the allometric scaling factor for the rat is 4;

(3) a default factor of 2.5 accounts for additional interspecies differences;

(4) for intraspecies differences the default factor is 5 for workers and for consumers is 10

 

Applying these factors to the oral NOAEL gives:

 

DNEL dermal, systemic, chronic worker = 996/300 = 3.32 mg/kg bw/day

 

DNEL dermal, systemic, chronic consumers= 996/600 = 1.66 mg/kg bw/day

 

Oral exposure

Starting point is NOAEL of 996 mg/kg/day from a 28 -day rat study. Assuming 100% absorption and the AF described above, critical exposure levels are as follows:

DNEL oral, systemic, chronic general population = 996/600= 1.66 mg/kg/day

 

No oral exposure is considered for workers.

Inhalatory exposure

For the chronic inhalation exposure DNELs, the corrected NOAEL was derived as a starting point based on the oral NOAEL of 996 mg/kg bw/day, since no study data were available from long term repeated exposure investigations via the inhalation route. This route is considered of minor concern due to the vapour pressure of the substance.

The total assessment factor for the worker population, long term DNEL inhalation, systemic = 6*2.5*5*1*1 = 75 when the subacute to chronic factor is included.

 

The total assessment factor for the general population, long term DNEL inhalation, systemic = 6*2.5*10*1*1 = 150 when the subacute to chronic factor is included.

 

Differences in respiration volumes were assessed for converting the oral dose to an inhalation concentration:

 

Worker Population - NOAEL of 996 mg/kg/d /0.38m3/kg = 2621 * [6.7 m3/ 10 m3] = 1756 mg/m3.

General Population - NOAEL of 996 mg/kg/d /1.15m3/kg = 866 mg/m3

 

Applying the above explained AF:

 

DNEL inhalation, systemic, chronic worker population = 1756 / 75 = 23.4 mg/m3

DNEL inhalation, systemic, chronic general population = 866 / 150 = 5.77 mg/m3 

The default absorption percentage 100%, for inhalation has also been used in the calculations.