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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
32.4 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:
1 610 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
809 mg/m³
Explanation for the modification of the dose descriptor starting point:

Conversion of an rat NOAECinhalatory; rep. dosefrom 90 day rat inhalativ repeated dose toxicity study into an corrected NOAECinhalatory; rep. dose (derived from figure R.8-2; Chapter R 8.4.2 of TGD “Chapter R.8: Characterisation of dose [concentration]-response for human health”):

 

For workers:

assumptions:

8 h exposure/day

Inhalation absorption rat = inhalation absorption human

 

corrected NOAECinhalatory; rep.dose        = rat NOAECinhalatory; rep. dose* ((6 h/d) / (8 h/d)) * ((6.7 m3 (8h)) / 10 m3 (8h))

                                                                               = 1610 mg/m3* 0.75 * 0.67

                                                                               = 809 mg/m3

AF for dose response relationship:
1
Justification:
default assessment factor 1, because the starting point is a NOAEC, Chapter R 8.4.3.1 of ECHA REACH Guidance
AF for differences in duration of exposure:
2
Justification:
According to Chapter R.8 of ECHA REACH Guidance, Table 8-5 the default assessment factor for subchronic to chronic duration is 2.
AF for interspecies differences (allometric scaling):
1
Justification:
For an inhalation study already scaled according to the allometric principle, Chapter R 8.4.3.1 of ECHA REACH Guidance
AF for other interspecies differences:
2.5
Justification:
default assessment factor for remaining interspecies differences in case for systemic effects, Chapter R 8.4.3.1 of ECHA REACH Guidance
AF for intraspecies differences:
5
Justification:
default assessment factor for workers, Chapter 8.4.3.1 of ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
default assessment factor for good quality of the database, Chapter 8.4.3.1 of ECHA REACG Guidance
AF for remaining uncertainties:
1
Justification:
No further assessment factors are considered necessary.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
32.4 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL extrapolated from long term DNEL

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:
repeated dose toxicity
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.1 mg/kg bw/day
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):
100
Dose descriptor starting point:
NOAEL
Value:
809 mg/m³
Modified dose descriptor starting point:
NOAEL
Value:
307 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Converting the inhalatory NOAEL rat into a dermal NOAEL is necessary to derive the correct starting point for the

dermal route for which no long term study was carried out.

Conversion of an rat NOAELinhal; rep. dosefrom 90 day rat inhalative repeated dose toxicity study into an corrected NOAELderm; rep.dose (derived from examples B.4 and B.5; Appendix R 8-2 of TGD “Chapter R.8: Characterisation of dose [concentration]-response for human health”):

 

For worker:

assumptions:

- No default factor for absorption should be introduced (i.e. factor 1) in case of inhalation-to-oral extrapolation according to Chapter R.8.4.2 of TGD)

- On the assumption that, in general, dermal absorption will not be higher than oral absorption, no default factor for absorption should be introduced when performing oral-to-dermal extrapolation according to Chapter R.8.4.2 of TGD).

 

corrected NOAELoral; rep. dose = corrNOAELinhal; rep.dose * sRVrat * (ABSinhal-rat/ABSoral-human)

= 809 mg/m3 * 0.38 m3/kg bw * 1

= 307 mg/kg bw

corrected NOAELderm; rep.dose= corrNOAELoral; rep. dose* (ABSoral/ ABSderm)

                                                                              

                                               = 307 mg/kg bw day * 1

 

                                               = 307 mg/kg bw day

AF for dose response relationship:
1
Justification:
Starting point for the DNEL calculation is a NOAEL. Thus standard assessment factor 1 is used as described in chapter R 8.4.3.1 of TGD (ECHA, Nov. 2012).
AF for differences in duration of exposure:
2
Justification:
A assessment factor 2 is suggested by the ECHA TGD for exposure duration from subchronic to chronic (see section R 8.4.3.1, Table R.8-5) (ECHA, Nov. 2012).
AF for interspecies differences (allometric scaling):
4
Justification:
An allometric scaling factor of 4 is suggested by the ECHA TGD (see section 8.4.3.1 of TGD; ECHA, Nov. 2012) for interspecies differences.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is suggested by the ECHA TGD (ECHA, Nov. 2012) for remaining interspecies differences.
AF for intraspecies differences:
5
Justification:
For intraspecies variability, the default assessment factor for worker for systemic effects is 5 (ECHA, Nov. 2012).
AF for the quality of the whole database:
1
Justification:
Because of good/standard quality of the database the standard assessment factor 1 is used as described in chapter R 8.4.3.1 of TGD (ECHA, Nov. 2012).
AF for remaining uncertainties:
1
Justification:
No further assessment factors are considered necessary.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
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

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.05 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:
1 610 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
402.5 mg/m³
Explanation for the modification of the dose descriptor starting point:

No route-to-route-extrapolation is needed

Conversion of an rat NOAECinhalatory; rep. dosefrom 90 day rat inhalativ repeated dose toxicity study into an corrected NOAECinhalatory; rep. dose  for general population (derived from figure R.8-2; Chapter R 8.4.2 of TGD “Chapter R.8: Characterisation of dose [concentration]-response for human health”):

 

For general population:

assumptions:

24 h exposure/day

Inhalation absorption rat = inhalation absorption human

 

corrected NOAECinhalatory; rep.dose        = rat NOAECinhalatory; rep. dose* ((6 h/d) / (24 h/d))

                                                                               = 1610 mg/m3* 0.25

                                                                               = 402.5 mg/m3

AF for dose response relationship:
1
Justification:
Starting point is a NOAEC. Thus standard assessment factor 1 is used as described in chapter R 8.4.3.1 of ECHA TGD (ECHA, Nov. 2012).
AF for differences in duration of exposure:
2
Justification:
According to Chapter R.8 of ECHA REACH Guidance, Table 8-5 the default assessment factor for subchronic to chronic duration is 2.
AF for interspecies differences (allometric scaling):
1
Justification:
According to ECHA TGD (ECHA, Nov. 2012) an allometric scaling factor is not applicable when setting an inhalation DNEL based on an inhalation animal study (see Appendix R.8-2), therefore AF 1 is chosen.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is suggested by the ECHA TGD (ECHA, Nov. 2012) for remaining interspecies differences.
AF for intraspecies differences:
10
Justification:
For intraspecies variability, the default assessment factor for general population for systemic effects is 10 (ECHA, Nov. 2012).
AF for the quality of the whole database:
1
Justification:
Because of good/standard quality of the database the standard assessment factor 1 is used as described in chapter R 8.4.3.1 of ECHA TGD (ECHA, Nov. 2012).
AF for remaining uncertainties:
1
Justification:
No further assessment factors are considered necessary.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.05 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL extrapolated from long term DNEL

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:
0.5 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No route-to-route-extrapolation needed

Conversion of an rat NOAELoral; rep. dosefrom developmental toxicity study into an humanNOAELoral; rep. dose (derived from example A.1; Appendix R 8-2 of TGD “Chapter R.8: Characterisation of dose [concentration]-response for human health”):

 

For general population:

assumptions:

absorptionoral-rat= absorptionoral-human

 

human NOAELoral; rep.dose= rat NOAELoral; rep. dose  = 300 mg/kg bw day

AF for dose response relationship:
1
Justification:
Starting point for the DNEL calculation is a NOAEC. Thus standard assessment factor 1 is used as described in chapter R 8.4.3.1 of TGD (ECHA, Nov. 2012).
AF for differences in duration of exposure:
6
Justification:
A assessment factor 6 is suggested by the ECHA TGD for exposure duration from subacute to chronic (see section R 8.4.3.1, Table R.8-5) (ECHA, Nov. 2012).
AF for interspecies differences (allometric scaling):
4
Justification:
An allometric scaling factor of 4 is suggested by the ECHA TGD (see section 8.4.3.1 of TGD; ECHA, Nov. 2012) for interspecies differences.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is suggested by the ECHA TGD (ECHA, Nov. 2012) for remaining interspecies differences.
AF for intraspecies differences:
10
Justification:
For intraspecies variability, the default assessment factor for the general population is 10 (ECHA, Nov. 2012).
AF for the quality of the whole database:
1
Justification:
Because of good/standard quality of the database the standard assessment factor 1 is used as described in chapter R 8.4.3.1 of TGD (ECHA, Nov. 2012).
AF for remaining uncertainties:
1
Justification:
No further assessment factors are considered necessary.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.5 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL extrapolated from long term DNEL

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population