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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
14.69 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):
18
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
264.47 mg/m³
Explanation for the modification of the dose descriptor starting point:

Starting point us the oral NOAEL of 300 mg/kg bw. A factor of 2 is applied for route to route extrapolation: oral to inhalation. For animal versus human exposure the following formula is applied: 150*(1/0.38)*6.7/10) = 264.47 mg/m3.

AF for dose response relationship:
1
Justification:
No additional assessment factor for dose response is needed because the dosing was well spaced in the study and a NOAEL in the OECD TG 422 study was derived (ECHA’s guidance, R.8.4.3.1, November, 2012).
AF for differences in duration of exposure:
6
Justification:
Since the dose descriptor is derived from an oral OECD TG 422 feeding study, an additional assessment factor of 6 is used to take the extrapolation of subacute data to chronic exposure into account (ECHA 2012, Chapter R8, p 29)
AF for interspecies differences (allometric scaling):
1
Justification:
An assessment factor of 1 has been used because the difference in metabolic rate between rat and humans has been accounted for in the conversion of NOAEL in mg/kg bw to the NOEC mg/m3, as presented in ECHA’s guidance R.8, figure R. 8-2 (November, 2012).
AF for other interspecies differences:
1
Justification:
An assessment factor of 1 has been applied because besides allometric differences no other interspecies differences need to be accounted for which has been shown by ECETOC TR 110 (2010) after a review of the scientific literature. ECETOC concludes that adjusting animal dose by allometric scaling predicts reasonably well the appropriate dose in humans. The application the ‘remaining’ AF of 2.5 for interspecies variability would mean an unjustified complication of AF. The ‘residual’ interspecies variability may remain following allometric scaling, but this is largely accounted for in the default AF proposed for intraspecies variability, i.e. reflecting the interdependency of inter- and intraspecies AF.
AF for intraspecies differences:
3
Justification:
ECETOC TR No. 110 (2010) the intraspecies variation in humans is greater than that in the more homogenous experimental animal population. Based on an evaluation of the scientific literature by ECETOC, an AF of 3 (for workers) and of 5 (for the general population is advised, after a detailed review of the literature.
AF for the quality of the whole database:
1
Justification:
An assessment factor of 1 is applicable because the information fulfils the REACH requirements: an OECD TG 422 study according to OECD guideline (and GLP) (ECHA’s Guidance, R.8.4.3.1, November, 2012).
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties were 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
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.17 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):
72
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Based on the toxico-kinetic information it can be anticipated that dermal absorption is expected to be lower than dermal absorption and will not exceed oral absorption. Therefore the starting dose descriptor is the same: 300 mg/kg bw.

AF for dose response relationship:
1
Justification:
No additional assessment factor for dose response is needed because the dosing was well spaced in the study and a NOAEL in the OECD TG 422 study was derived (ECHA’s guidance, R.8.4.3.1, November, 2012).
AF for differences in duration of exposure:
6
Justification:
Since the dose descriptor is derived from an OECD TG 422 study, an additional assessment factor of 6 to take account of extrapolation of sub-acute data to chronic exposure (ECHA 2012, Chapter R8, p 29).
AF for interspecies differences (allometric scaling):
4
Justification:
For allometric scaling a factor of 4 is applicable to convert rat to human data, as determined by ECHA 2012, Chapter 8 (Table R.8-3).
AF for other interspecies differences:
1
Justification:
Additional assessment factors for interspecies differences are not needed as has been derived in the ECETOC report (TR 110, 2010) based on a review of the scientific literature. The concept of adjusting animal dose by allometric scaling predicts reasonably well the appropriate dose in humans. A Geometric Standard Deviation (GSD) of 2.5-2.6 suggests the likelihood of some variability or additional uncertainty around the predicted NOAEL in humans. This analysis is based on a comparison of animal to actual human data that per se includes intraspecies variability in humans (see below at intraspecies differences).
AF for intraspecies differences:
3
Justification:
ECETOC TR No. 110 (2010) the intraspecies variation in humans is greater than that in the more homogenous experimental animal population. Based on an evaluation of the scientific literature by ECETOC, an AF of 3 (for workers) and of 5 (for the general population is advised, after a detailed review of the literature.
AF for the quality of the whole database:
1
Justification:
An assessment factor of 1 is applicable because the information fulfils the REACH requirements: an OECD TG 422 study according to OECD guideline (and GLP) (ECHA’s Guidance, R.8.4.3.1, November, 2012).
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties were identified.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.35 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):
30
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
130.43 mg/m³
Explanation for the modification of the dose descriptor starting point:

Starting point is the NOAEL of 300 mg/kg bw. A factor of 2 is applied for route-to-route extrapolation: oral to inhalation. In addition, for rat to human extrapolation the following formula is used: 150 mg/kg bw /1.15 = 130.43 mg/m3.

AF for dose response relationship:
1
Justification:
No additional assessment factor for dose response is needed because the dosing was well spaced in the study and a NOAEL in the OECD TG 422 study was derived (ECHA’s guidance, R.8.4.3.1, November, 2012).
AF for differences in duration of exposure:
6
Justification:
Since the dose descriptor is derived from a OECD TG 422 study, an additional assessment factor of 6 to take account of extrapolation of sub-acute data to chronic exposure (ECHA 2012, Chapter R8, p 29).
AF for interspecies differences (allometric scaling):
1
Justification:
An assessment factor of 1 has been used because the difference in metabolic rate between rat and humans has been accounted for in the conversion of NOAEL in mg/kg bw to the NOAEC in mg/m3, as presented in ECHA’s guidance R.8, figure R. 8-2 (November, 2012).
AF for other interspecies differences:
1
Justification:
An assessment factor of 1 has been applied because besides allometric differences no other interspecies differences need to be accounted for which has been shown by ECETOC TR 110 (2010) after a review of the scientific literature. ECETOC concludes that adjusting animal dose by allometric scaling predicts reasonably well the appropriate dose in humans. The application the ‘remaining’ AF of 2.5 for interspecies variability would mean an unjustified compilation of AF. The ‘residual’ interspecies variability may remain following allometric scaling, but this is largely accounted for in the default AF proposed for intraspecies variability, i.e. reflecting the interdependency of inter- and intraspecies AF.
AF for intraspecies differences:
5
Justification:
ECETOC TR No. 110 (2010) The intraspecies variation in humans is greater than that in the more homogenous experimental animal population. Based on an evaluation of the scientific literature by ECETOC, an AF of 3 (for workers) and of 5 (for the general population is advised, after a detailed review of the literature.
AF for the quality of the whole database:
1
Justification:
An assessment factor of 1 is applicable because the information fulfils the REACH requirements: a 28-day study according to OECD guideline (and GLP) (ECHA’s Guidance, R.8.4.3.1, November, 2012).
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties were 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
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.5 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):
120
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Based on the toxico-kinetic information it can be anticipated that dermal absorption is expected to be lower than dermal absorption and will not exceed oral absorption. Therefore the starting dose descriptor is the same: 300 mg/kg bw.

AF for dose response relationship:
1
Justification:
No additional assessment factor for dose response is needed because the dosing was well spaced in the study and a NOAEL was derived from the OECD TG 422 study (ECHA’s guidance, R.8.4.3.1, November, 2012).
AF for differences in duration of exposure:
6
Justification:
Since the dose descriptor is derived from a OECD TG 422 study, an additional assessment factor of 6 to take account of extrapolation of sub-acute data to chronic exposure (ECHA 2012, Chapter R8, p 29)
AF for interspecies differences (allometric scaling):
4
Justification:
For allometric scaling a factor of 4 is applicable to convert rat to human data, as determined by ECHA 2012, Chapter 8 (Table R.8-3)
AF for other interspecies differences:
1
Justification:
Additional assessment factors for interspecies differences are not needed as has been derived in the ECETOC report (TR 110, 2010) based on a review of the scientific literature. The concept of adjusting animal dose by allometric scaling predicts reasonably well the appropriate dose in humans. A Geometric Standard Deviation (GSD) of 2.5-2.6 suggests the likelihood of some variability or additional uncertainty around the predicted NOAEL in humans. This analysis is based on a comparison of animal to actual human data that per se includes intraspecies variability in humans (see below at intraspecies differences).
AF for intraspecies differences:
5
Justification:
ECETOC TR No. 110 (2010). The intraspecies variation in humans is greater than that in the more homogenous experimental animal population. Based on an evaluation of the scientific literature by ECETOC, an AF of 3 (for workers) and of 5 (for the general population) is advised.
AF for the quality of the whole database:
1
Justification:
An assessment factor of 1 is applicable because the information fulfils the REACH requirements: a 28-day study according to OECD guideline (and GLP) (ECHA’s Guidance, R.8.4.3.1, November, 2012).
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties were identified.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.5 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):
120
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The substance fulfils the REACH Annex VII to Annex XI information requirements in accordance with R.7.5-7.7 for assessing long-term systemic toxicity. The NOAEL from a >28-day repeated dose /reproscreen toxicity study is used to derive a DNEL. A DNEL derivation for the oral route is considered necessary, because oral exposure via the environment cannot be excluded.

AF for dose response relationship:
1
Justification:
No additional assessment factor for dose response is needed because the dosing was well spaced in the study and a NOAEL was derived from the OECD TG 422 study (ECHA’s guidance, R.8.4.3.1, November, 2012).
AF for differences in duration of exposure:
6
Justification:
Since the dose descriptor is derived from a OECD TG 422 study, an additional assessment factor of 6 to take account of extrapolation of sub-acute data to chronic exposure (ECHA 2012, Chapter R8, p 29)
AF for interspecies differences (allometric scaling):
4
Justification:
For allometric scaling a factor of 4 is applicable to convert rat to human data. ECETOC (TR110, 2010) after a review of the scientific literature. ECETOC concludes that adjusting animal dose by allometric scaling predicts reasonably well the appropriate dose in humans.
AF for other interspecies differences:
1
Justification:
Additional assessment factors for interspecies differences are not needed as has been derived in the ECETOC report (TR 110, 2010) based on a review of the scientific literature. The concept of adjusting animal dose by allometric scaling predicts reasonably well the appropriate dose in humans. A Geometric Standard Deviation (GSD) of 2.5-2.6 suggests the likelihood of some variability or additional uncertainty around the predicted NOAEL in humans. This analysis is based on a comparison of animal to actual human data that per se includes intraspecies variability in humans (see below at intraspecies differences).
AF for intraspecies differences:
5
Justification:
ECETOC TR No. 110 (2010) the intraspecies variation in humans is greater than that in the more homogenous experimental animal population. Based on an evaluation of the scientific literature by ECETOC, an AF of 3 (for workers) and of 5 (for the general population is advised, after a detailed review of the literature.
AF for the quality of the whole database:
1
Justification:
An assessment factor of 1 is applicable because the information fulfils the REACH requirements: a 28-day study according to OECD guideline (and GLP) (ECHA’s Guidance, R.8.4.3.1, November, 2012).
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties were identified.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population