Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
13.05 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:
1 110 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
978.55 mg/m³
Explanation for the modification of the dose descriptor starting point:

According to the ECHA Guidance on IR&CSA, Chapter R.8, the standard respiratory volume (sRV) for the rat was calculated from the sRV for humans (per kg bw; average human bodyweight 70 kg) and applying the corresponding allometric scaling factor for the rat of 4. The modified NOAEC was then further calculated according to the guidance.

sRV(rat, 8h) = sRV(human, 8h) x allometric scaling factor = (6.7m³/70kg bw) x 4 = 0.38 m³/kg bw/d

NOAEC,modified (worker, 8h) = NOAEL,oral * [1/sRV(rat)] * [absorption (ABS),oral-rat / ABS(inh-human)] * [sRV(human) / worker Respiratory Volume (wRV)]

NOAEC,modified (worker, 8h) = 1110 mg/kg bw/d * [1/0.38 m³/kg bw/d] * [0.5 / 1] * [6.7 m³ (8h) / 10 m³ (8h)]

NOAEC,modified = 978.55 mg/m³

AF for dose response relationship:
1
Justification:
The starting point for the DNEL calculation is a NOAEL. Therefore, the default assessment factor 1 is chosen.
AF for differences in duration of exposure:
6
Justification:
The default AF of 6 for time extrapolation between sub-acute (28d) to chronic study duration is set in line with the REACH guidance R.8.
AF for interspecies differences (allometric scaling):
1
Justification:
The AF has already been handled within the correction of the modification of the dose descriptor.
Therefore, no additional factor has to be applied.
AF for other interspecies differences:
2.5
Justification:
The default AF of 2.5 for other interspecies differences, i.e. toxicokinetic/-dynamic differences is used.
AF for intraspecies differences:
5
Justification:
The default factor of 5 for workers is set in line with the REACH guidance.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3 mg/m³
DNEL related information
DNEL derivation method:
other: dust limit value (as in ECHA Guidance R8)
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:
3.7 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:
1 110 mg/m³
Modified dose descriptor starting point:
NOAEL
Value:
1 110 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

There are no substance-specific information relating to differences in bioavailability available. Following guideline R.8, it is assumed that in general, dermal absorption will not be higher than oral absorption. Therefore, no factor (i.e. factor 1) is introduced for the extrapolation of oral-to-dermal route.

AF for dose response relationship:
1
Justification:
The starting point for the DNEL calculation is a NOAEL. Therefore, the default assessment factor 1 is chosen.
AF for differences in duration of exposure:
6
Justification:
The default AF of 6 for time extrapolation between sub-acute (28d) to chronic study duration is set in line with the REACH guidance R.8.
AF for interspecies differences (allometric scaling):
4
Justification:
The default AF of 4 for rats for interspecies differences is used.
AF for other interspecies differences:
2.5
Justification:
The default AF of 2.5 for other interspecies differences, i.e. toxicokinetic/-dynamic differences is used.
AF for intraspecies differences:
5
Justification:
The default factor of 5 for workers is set in line with the REACH guidance R.8.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
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

1. Identification of relevant dose descriptor

In an OECD 422 study performed in rats, the structural analogue did not cause mortalities, signs of toxicity or any other changes or abnormalities. The NOEL is considered to be 1110 mg/kg bw/d.

2. Mode of action

No non-threshold mode of action is associated with the test substance. In particular, the test substance has no genotoxic potential.

3. Application of assessment factors

Allometric scaling: rat to human = 4

Interspecies factor (remaining differences): 2.5

Intraspecies factor: worker = 5, general population = 10

Exposure duration subacute to chronic: 6

Quality of data base: 1

Dose response: 1

4. Daily exposure

Worker: exposed for 8h

General population: exposed for 24h

Calculation of DNEL bases upon Guidance Document on Dermal Absorption, European Commission, 2004 and Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health, may 2008

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.74 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:
1 110 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
411.11 mg/m³
Explanation for the modification of the dose descriptor starting point:

According to the ECHA Guidance on IR&CSA, Chapter R.8, the standard respiratory volume (sRV) for the rat was calculated from the sRV for humans (per kg bw; average human bodyweight 60 kg) and applying the corresponding allometric scaling factor for the rat of 4. The modified NOAEC was then further calculated according to the guidance.

sRV(rat, 8h) = sRV(human, 8h) x allometric scaling factor = (6.7m³/60kg bw) x 4 = 1.35 m³/kg bw/8h

NOAEC,modified (general pop., 8h) = NOAEL,oral * [1/sRV(rat)] * [absorption (ABS),oral-rat / ABS(inh-human)] * [sRV(human) / general pop. Respiratory Volume (wRV)]

NOAEC,modified (general pop., 8h) = 1110 mg/kg bw/d * [1/1.35 m³/kg bw/8h] * [0.5 / 1]

NOAEC,modified = 411.11 mg/m³

AF for dose response relationship:
1
Justification:
The starting point for the DNEL calculation is a NOAEL. Therefore, the default assessment factor 1 is chosen.
AF for differences in duration of exposure:
6
Justification:
The default AF of 6 for time extrapolation between sub-acute (28d) to chronic study duration is set in line with the REACH guidance R.8.
AF for interspecies differences (allometric scaling):
1
Justification:
The AF has already been handled within the correction of the modification of the dose descriptor.
Therefore, no additional factor has to be applied.
AF for other interspecies differences:
2.5
Justification:
The default AF of 2.5 for other interspecies differences, i.e. toxicokinetic/-dynamic differences is used.
AF for intraspecies differences:
10
Justification:
The default factor of 10 for the general population is set in line with the REACH guidance R.8.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
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:
1.85 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:
1 110 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 110 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

There are no substance-specific information relating to differences in bioavailability available. Following guideline R.8, it is assumed that in general, dermal absorption will not be higher than oral absorption. Therefore, no factor (i.e. factor 1) is introduced for the extrapolation of oral-to-dermal route.

AF for dose response relationship:
1
Justification:
The starting point for the DNEL calculation is a NOAEL. Therefore, the default assessment factor 1 is chosen.
AF for differences in duration of exposure:
6
Justification:
The default AF of 6 for time extrapolation between sub-acute (28d) to chronic study duration is set in line with the REACH guidance R.8.
AF for interspecies differences (allometric scaling):
4
Justification:
The default AF of 4 for rats for interspecies differences is used.
AF for other interspecies differences:
2.5
Justification:
The default AF of 2.5 for other interspecies differences, i.e. toxicokinetic/-dynamic differences is used.
AF for intraspecies differences:
10
Justification:
The default factor of 10 for the general population is set in line with the REACH guidance R.8.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
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:
1.85 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:
1 110 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 110 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

There is no extrapolation for rout-to-route necessary.

AF for dose response relationship:
1
Justification:
The starting point for the DNEL calculation is a NOAEL. Therefore, the default assessment factor 1 is chosen.
AF for differences in duration of exposure:
6
Justification:
The default AF of 6 for time extrapolation between sub-acute (28d) to chronic study duration is set in line with the REACH guidance R.8.
AF for interspecies differences (allometric scaling):
4
Justification:
The default AF of 4 for rats for interspecies differences is used.
AF for other interspecies differences:
2.5
Justification:
The default AF of 2.5 for other interspecies differences, i.e. toxicokinetic/-dynamic differences is used.
AF for intraspecies differences:
10
Justification:
The default factor of 10 for the general population is set in line with the REACH guidance R.8.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
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

1. Identification of relevant dose descriptor

In an OECD 422 study performed in rats, the structural analogue did not cause mortalities, signs of toxicity or any other changes or abnormalities. The NOEL is considered to be 1110 mg/kg bw/d.

2. Mode of action

No non-threshold mode of action is associated with the test substance. In particular, the test substance has no genotoxic potential.

3. Application of assessment factors

Allometric scaling: rat to human = 4

Interspecies factor (remaining differences): 2.5

Intraspecies factor: worker = 5, general population = 10

Exposure duration subacute to chronic: 6

Quality of data base: 1

Dose response: 1

4. Daily exposure

Worker: exposed for 8h

General population: exposed for 24h

Calculation of DNEL bases upon Guidance Document on Dermal Absorption, European Commission, 2004 and Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health, may 2008