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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
0.71 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:
15 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
52.9 mg/m³
Explanation for the modification of the dose descriptor starting point:

Modification of the dose descriptors is necessary, because the routes of exposure are different between animals (oral) and humans (inhalation). For this purpose the default respiratory volume for the rat corresponding to the daily duration of human exposure is considered in the first step, followed by a correction for the difference between respiratory rates of workers under standard conditions and under light activity in the second step, followed by a correction for the difference in oral absorption in the rat and inhalation absorption in humans.

In accordance with ECHA Guidance Chapter R.8: Characterisation of dose [concentration]-response for human health, Example B.3, the following equation is used for workers to convert the oral NOAEL rat (15 mg/kg bw/day - the lowest NOAEL value, obtained in the 28 day study as a worst case) into the inhalatory NOAEC rat:

NAECcorr_inh = oral NOAEL x (1/sRVrat) x (ABSoral-rat/ABSinhalation-human) x (sRVhuman/wRV)

Where:

ABS: Absorption;

sRVrat: standard Respiratory Volume (rat) = 0.38 m3/kg bw/day (8 hours);

sRVhuman: standard Respiratory Volume (human) = 6.7 m3

wRV: worker Respiratory Volume = 10 m3

Therefore NAECcorr_inh = 15 x (1/0.38) x (ABSoral-rat/ABSinhalation-human) x (6.7/10)

Oral absorption in rats/humans is assumed to be 100% and inhalation absorption in rats/humans is assumed to be 100% (see IUCLID Chapter 7.1, Toxicokinetics), however, in compliance with ECHA guidance, for the purposes of extrapolation from the oral to the inhalation route, it is assumed that oral absorption in rats is 100% and inhalation absorption in humans is 50% as a worst case.

NAECcorr_inh = 15 x (1/0.38) x (100/50) x (6.7/10) = 52.9 mg/m3.

AF for dose response relationship:
1
Justification:
Default factor when a NOAEL value is available, in accordance with REACH Guidance R.8
AF for differences in duration of exposure:
6
Justification:
Default assessment factor for extrapolation from subacute to chronic
Justification:
No allometric scaling required for inhalation route.
AF for other interspecies differences:
2.5
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for intraspecies differences:
5
Justification:
Default factor for workers, in accordance with REACH Guidance R.8
AF for the quality of the whole database:
1
Justification:
Default factor for good quality database (Klimisch 1 study), in accordance with REACH Guidance R.8
AF for remaining uncertainties:
1
Justification:
Default factor, in accordance with REACH Guidance R.8
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:
0.125 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:
15 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
37.5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

In accordance with ECHA Guidance Chapter R.8: Characterisation of dose [concentration]-response for human health, Example B.5, the following equation is used to convert the oral NOAEL rat (15 mg/kg bw/day - the lowest NOAEL value, obtained in the 28 day study as a worst case) into the dermal NOAEL rat:

corrected dermal NOAEL = oral NOAEL x ABSoral-rat/ABSdermal-human

Where:

ABS: Absorption

The oral absorption in rats is assumed to be 100% and the dermal absorption in humans is assumed to be 40% - see IUCLID Chapter 7.1, Toxicokinetics.

Therefore, the corrected dermal NOAEL = 15 x 100/40 = 37.5 mg/kg bw/day

AF for dose response relationship:
1
Justification:
Default factor when a NOAEL value is available, in accordance with REACH Guidance R.8
AF for differences in duration of exposure:
6
Justification:
Default assessment factor for extrapolation from subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor (rat to human), in accordance with REACH Guidance R.8
AF for other interspecies differences:
2.5
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for intraspecies differences:
5
Justification:
Default factor for workers, in accordance with REACH Guidance R.8
AF for the quality of the whole database:
1
Justification:
Default factor for good quality database (Klimisch 1 study), in accordance with REACH Guidance R.8
AF for remaining uncertainties:
1
Justification:
Default factor, in accordance with REACH Guidance R.8
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

The lowest NOAEL for this substance was obtained in the 28 day oral repeated dose toxicity study (15 mg/kg bw/day); as a worst case, this NOAEL was selected as the starting point for deriving the long-term systemic inhalation DNEL and the long-term systemic dermal DNEL. Acute systemic dermal/inhalation DNELs and local inhalation DNELs were not derived because the substance is not classified for acute dermal or inhalation toxicity and it is considered that derivation from long term systemic effects provides a suitable margin for safety of use.

The substance is classified as a Skin Irritant Category 2, however, no dose response data are available therefore a qualitative risk assessment has been conducted for local dermal effects.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.17 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:
15 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
26.1 mg/m³
Explanation for the modification of the dose descriptor starting point:

Modification of the dose descriptors is necessary, because the routes of exposure are different between animals (oral) and humans (inhalation). For this purpose the default respiratory volume for the rat corresponding to the daily duration of human exposure is considered in the first step, followed by a correction for the difference in oral absorption in the rat and inhalation absorption in humans.

In accordance with ECHA Guidance Chapter R.8: Characterisation of dose [concentration]-response for human health, Figure R. 8-3, the following equation is used for the general population to convert the oral NOAEL rat (15 mg/kg bw/day - the lowest NOAEL value, obtained in the 28 day study as a worst case) into the inhalatory NOAEC rat:

NAECcorr_inh = oral NOAEL x (1/sRVrat) x (ABSoral-rat/ABSinhalation-human)

Where:

ABS: Absorption;

sRVrat: standard Respiratory Volume (rat) = 1.15 m3/kg bw/day (24 hours)

Therefore NAECcorr_inh = 15 x (1/1.15) x (ABSoral-rat/ABSinhalation-human)

Oral absorption in rats/humans is assumed to be 100% and inhalation absorption in rats/humans is assumed to be 100% (see IUCLID Chapter 7.1, Toxicokinetics), however, in compliance with ECHA guidance, for the purposes of extrapolation from the oral to the inhalation route, it is assumed that oral absorption in rats is 100% and inhalation absorption in humans is 50% as a worst case.

NAECcorr_inh = 15 x (1/1.15) x (100/50) = 26.1 mg/m3.

AF for dose response relationship:
1
Justification:
Default factor when a NOAEL value is available, in accordance with REACH Guidance R.8
AF for differences in duration of exposure:
6
Justification:
Default assessment factor for extrapolation from subacute to chronic
Justification:
No allometric scaling required for inhalation route.
AF for other interspecies differences:
2.5
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for intraspecies differences:
10
Justification:
Default factor for general population, in accordance with REACH Guidance R.8
AF for the quality of the whole database:
1
Justification:
Default factor for good quality database (Klimisch 1 study), in accordance with REACH Guidance R.8
AF for remaining uncertainties:
1
Justification:
Default factor, in accordance with REACH Guidance R.8
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:
0.062 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:
15 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
37.5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

In accordance with ECHA Guidance Chapter R.8: Characterisation of dose [concentration]-response for human health, Example B.5, the following equation is used to convert the oral NOAEL rat (15 mg/kg bw/day - the lowest NOAEL value, obtained in the 28 day study as a worst case) into the dermal NOAEL rat:

corrected dermal NOAEL = oral NOAEL x ABSoral-rat/ABSdermal-human

Where:

ABS: Absorption

The oral absorption in rats is assumed to be 100% and the dermal absorption in humans is assumed to be 40% - see IUCLID Chapter 7.1, Toxicokinetics.

Therefore, the corrected dermal NOAEL = 15 x 100/40 = 37.5 mg/kg bw/day

AF for dose response relationship:
1
Justification:
Default factor, when a NOAEL is available, in accordance with REACH Guidance R.8
AF for differences in duration of exposure:
6
Justification:
Default assessment factor for extrapolation from subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor (rat to human), in accordance with REACH Guidance R.8
AF for other interspecies differences:
2.5
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for intraspecies differences:
10
Justification:
Default factor for general population, in accordance with REACH Guidance R.8
AF for the quality of the whole database:
1
Justification:
Default factor for good quality database (Klimisch 1 study), in accordance with REACH Guidance R.8
AF for remaining uncertainties:
1
Justification:
Default factor, in accordance with REACH Guidance R.8
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
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:
0.03 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:
15 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
15 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Assuming that oral absorption in rats is 100% and that oral absorption in humans is 100% as a worst case (see IUCLID Chapter 7.1 Toxicokinetics), modification of the dose descriptor starting point is not required.

AF for dose response relationship:
1
Justification:
Default factor, when NOAEL is available, in accordance with REACH Guidance R.8
AF for differences in duration of exposure:
6
Justification:
Default assessment factor for extrapolation from subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor (rat to human), in accordance with REACH Guidance R.8
AF for other interspecies differences:
2.5
Justification:
Default factor, in accordance with REACH Guidance R.8
AF for intraspecies differences:
10
Justification:
Default factor for general population, in accordance with REACH Guidance R.8
AF for the quality of the whole database:
1
Justification:
Default factor for good quality database (Klimisch 1 study), in accordance with REACH Guidance R.8
AF for remaining uncertainties:
1
Justification:
Default factor, in accordance with REACH Guidance R.8
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

The lowest NOAEL for this substance was obtained in the 28 day oral repeated dose toxicity study (15 mg/kg bw/day); as a worst case, this NOAEL was selected as the starting point for deriving the long-term systemic oral DNEL, the long-term systemic inhalation DNEL and the long-term systemic dermal DNEL. Acute systemic dermal/inhalation/oral DNELs and local inhalation DNELs were not derived because the substance is not classified for acute oral, dermal or inhalation toxicity and it is considered that derivation from long term systemic effects provides a suitable margin for safety of use.

The substance is classified as a Skin Irritant Category 2, however, no dose response data are available therefore a qualitative risk assessment has been conducted for local dermal effects.