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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
6.3 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:
128 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
112.8 mg/m³
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 ECHA guidance R7.5-7.7 (2016) for assessing long-term systemic toxicity. The substance does not need to be classified and labelled for systemic toxicity but adverse effects were seen in the repeated dose toxicity study. In absence of inhalation toxicity data the NOAEL from the 28-day repeated-dose oral toxicity study with reproduction/developmental toxicity screening is used for derivation of the DNEL-long-term for the inhalation route. Route-to route extrapolation can be done because there is adequate oral toxicity data; the critical effect is systemic rather than the site of contact. Also there is no evidence that the compound is subject to ‘first pass’ metabolism which would lead to higher inhalation toxicity compared to oral toxicity. To account for any uncertainties considering the toxicity potential via the oral and the inhalation route, the absorption via the inhalation route is chosen twice as high as the oral route (IGHRC, 2006 as mentioned in the ECHA guidance, R.8.4.2, November, 2012). Route-to-route extrapolation was applied in accordance with ECHA’s Guidance R.8. In the route to route extrapolation for the inhalation route a correction for respiratory volume is applied. The respiratory volume of rats (0.38 m3/kg bw) is multiplied by the respiratory volume of human (6.7 m3/person) and corrected for the respiratory volume for light activity to address the workers (10 m3/person).

AF for dose response relationship:
1
Justification:
Starting point is NOAEL.
AF for differences in duration of exposure:
6
Justification:
An assessment factor of 6 has been applied to extrapolate the NOAEL from a subacute study to a chronic study as presented in R.8.4.3.1 and table R.8-5 (ECHA's guidance, November, 2012).
AF for interspecies differences (allometric scaling):
1
Justification:
No correction for caloric demand for inhalation; is included in dose descriptor starting point.
AF for other interspecies differences:
1
Justification:
No remaining differences.
AF for intraspecies differences:
3
Justification:
An assessment factor of 3 has been used to account for the intraspecies differences. This factor has been retrieved by ECETOC (TR110, 2010). The ECETOC analysis has been based on a comparison between animal and actual human data that per se includes intraspecies variability in humans. In addition, the human population under investigation comprised cancer patients, this represents a very sensitive subpopulation. 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. Thus, this standard deviation represented by the GSD of 2.5-2.6 is probably due to potential differences in biological sensitivity between species, and includes intraspecies differences.
AF for the quality of the whole database:
1
Justification:
Reliable studies used.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
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:
1.8 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:
128 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
128 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 withR 7.5-7.7 (2016) for assessing long-term systemic toxicity. The substances is not classified and labelled for this endpoint but adverse effects are seen in the repeated dose toxicity study. The NOAEL from the 28-day repeated-dose oral toxicity study with reproduction/developmental toxicity screening is used for derivation of the DNEL long-term for the dermal route. No repeated dose dermal toxicity data are available. Route-to route extrapolation can be done because there is adequate oral toxicity data; the critical effect is systemic rather than at the site of contact. Also there is no evidence that the compound is subject to ‘first-pass’ metabolism which would lead to higher dermal toxicity compared to oral toxicity. To account for any uncertainties considering the toxicity potential via the oral and the dermal route, the absorption via the dermal route is the same as for the oral route, though some higher absorption is expected for the oral route (IGHRC, 2006 as mentioned in the ECHA guidance, R.8.4.2, November, 2012). In absence of dermal absorption information a factor of 1 for oral versus dermal absorption is applicable as proposed in ECHA guidance, Chapter R.8.4.2 (November, 2012).

AF for dose response relationship:
1
Justification:
Starting point is NOAEL.
AF for differences in duration of exposure:
6
Justification:
An assessment factor of 6 has been applied to extrapolate the NOAEL from a subacute study to a chronic study as presented in R.8.4.3.1 and table R.8-5 (ECHA's guidance, November, 2012).
AF for interspecies differences (allometric scaling):
4
Justification:
For allometric scaling a factor of 4 is applicable to convers 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:
No remaining differences.
AF for intraspecies differences:
3
Justification:
An assessment factor of 3 has been used to account for the intraspecies differences. This factor has been retrieved by ECETOC (TR110, 2010). The ECETOC analysis has been based on a comparison between animal and actual human data that per se includes intraspecies variability in humans. In addition, the human population under investigation comprised cancer patients, this represents a very sensitive subpopulation. A Geomatric Standard Deviation (GSD) of 2.5-2.6 suggests the likelihood of some variability or additional uncertainty around the predicted NOAEL in humans. Thus, this standard deviation represented by the GSD of 2.5-2.6 is probably due to potential differences in biological sensitivity between species, and includes intraspecies differences.
AF for the quality of the whole database:
1
Justification:
Reliable studies used.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
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:
medium hazard (no threshold derived)

Additional information - workers

In deriving the DNELs for hazard identification for inhalation and the dermal route of exposure mostly ECHA's guidance is used, which is generally conservative by using default values in absence of data outside the requirements of REACH regulation Annex VII to Annex XI. In addition, the used assessment factors used have been adequately documented. For inter and intraspecies assessment factors have been used which were conducted to be scientifically sound by ECETOC (TR 110, 2010) and which are based on a thorough review of the scientific literature. Therefore the DNELs for all human health endpoints relevant for workers are considered sufficiently conservative to be used in risk characterization.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.9 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:
128 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
55.7 mg/m³
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 ECHA guidance with R 7.5-7.7 (2016) for assessing long-term systemic toxicity. The substance does not need to be classified and labelled but adverse effects are seen in the repeated dose toxicity study. In absence of inhalation toxicity data the NOAEL from the 28-day repeated-dose oral toxicity study with reproduction/developmental toxicity screening is used for derivation of the DNEL-long-term for the inhalation route. Route-to route extrapolation can be done because there is adequate oral toxicity data, the critical effect is systemic rather than at the site of contact and there is no evidence that the compound is subject to ‘first pass’ metabolism which would lead to higher inhalation toxicity compared to oral toxicity. To account for any uncertainties considering the toxicity potential via the oral and the inhalation route, the absorption via the inhalation route is chosen twice as high as the oral route (IGHRC, 2006 as mentioned in the ECHA guidance, R.8.4.2, November, 2012) Route-to-route extrapolation was applied in accordance with ECHA’s Guidance R.8 (November, 2012). In the route to route extrapolation via the inhalation route a correction for respiratory volume is applied by using 1.15 m3/kg bw (ECHA’s guidance R.8, November, 2012).

AF for dose response relationship:
1
Justification:
Starting point is NOAEL.
AF for differences in duration of exposure:
6
Justification:
An assessment factor of 6 has been applied to extrapolate the NOAEL from a subacute study to a chronic study as presented in R.8.4.3.1 and table R.8-5 (ECHA's guidance, November, 2012).
AF for interspecies differences (allometric scaling):
1
Justification:
No correction for caloric demand for inhalation; is included in dose descriptor starting point.
AF for other interspecies differences:
1
Justification:
No remaining differences.
AF for intraspecies differences:
5
Justification:
An assessment factor of 5 has been used to account for the intraspecies differences as has been derived by ECETOC (TR110, 2010) based on a review of the scientific literature. The ECETOC analysis has been based on a comparison between animal and actual human data that per se includes intraspecies variability in humans. In addition, the human population under investigation comprised cancer patients, this represents a very sensitive subpopulation. 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. Thus, this standard deviation represented by the GSD of 2.5-2.6 is probably due to potential differences in biological sensitivity between species, and includes intraspecies differences.
AF for the quality of the whole database:
1
Justification:
Reliable studies used.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
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:
1.1 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:
128 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
128 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 ECHA guidance R.7.5-7.7. The substance does not need to be classified and labelled for systemic toxicity but adverse effects were seen in the repeated dose toxicity study. The NOAEL from the 28-day repeated-dose oral toxicity study with reproduction/developmental toxicity screening is used for derivation of the DNEL long-term for the dermal route because no long-term dermal information is available. Route-to route extrapolation can be done because there is adequate oral toxicity data; the critical effect is systemic rather than at the site of contact. There here is no evidence that the compound is subject to ‘first-pass’ metabolism which would lead to higher dermal toxicity compared to oral toxicity. To account for any uncertainties considering the toxicity potential via the oral and the dermal route, the absorption via the dermal route is the same as for the oral route, though some higher absorption is expected for the oral route (IGHRC, 2006 as mentioned in the ECHA guidance, R.8.4.2, November, 2012). In absence of dermal absorption information a factor of 1 for oral versus dermal absorption is applicable as proposed in ECHA guidance, Chapter R.8.4.2 (November, 2012).

AF for dose response relationship:
1
Justification:
Starting point is NOAEL.
AF for differences in duration of exposure:
6
Justification:
An assessment factor of 6 has been applied to extrapolate the NOAEL from a subacute study to a chronic study as presented in R.8.4.3.1 and table R.8-5 (ECHA's guidance, November, 2012).
AF for interspecies differences (allometric scaling):
4
Justification:
For allometric scaling a factor of 4 is applicable to convers 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. The application of 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 other interspecies differences:
1
Justification:
No remaining differences.
AF for intraspecies differences:
5
Justification:
An assessment factor of 5 has been used to account for the intraspecies differences as has been derived by ECETOC (TR110, 2010) based on a review of the scientific literature. The ECETOC analysis has been based on a comparison between animal and actual human data that per se includes intraspecies variability in humans. In addition, the human population under investigation comprised cancer patients, this represents a very sensitive subpopulation. A Geomatric Standard Deviation (GSD) of 2.5-2.6 suggests the likelihood of some variability or additional uncertainty around the predicted NOAEL in humans. Thus, this standard deviation represented by the GSD of 2.5-2.6 is probably due to potential differences in biological sensitivity between species, and includes intraspecies differences.
AF for the quality of the whole database:
1
Justification:
Reliable studies used.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
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:
1.1 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:
128 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 substance does not need to be classified and labelled for repeated dose effects but adverse effects are seen. The NOAEL from a 28-day repeated dose /reproscreen toxicity study is used to derive a DNEL.

The repeated dose toxicity test has been performed via the oral route and therefore route to route extrapolation is not needed, because there are no indications that rat has a different oral absorption compared to humans.

AF for dose response relationship:
1
Justification:
Starting point is NOAEL.
AF for differences in duration of exposure:
6
Justification:
An assessment factor of 6 has been applied to extrapolate the NOAEL from a subacute study to a chronic study as presented in R.8.4.3.1 and table R.8-5 (ECHA's guidance, November, 2012).
AF for interspecies differences (allometric scaling):
4
Justification:
For allometric scaling a factor of 4 is applicable to convers 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:
No remaining differences.
AF for intraspecies differences:
5
Justification:
An assessment factor of 5 has been used to account for the intraspecies differences as has been derived by ECETOC (TR110, 2010) based on a review of the scientific literature. The ECETOC analysis has been based on a comparison between animal and actual human data that per se includes intraspecies variability in humans. In addition, the human population under investigation comprised cancer patients, this represents a very sensitive subpopulation. A Geomatric Standard Deviation (GSD) of 2.5-2.6 suggests the likelihood of some variability or additional uncertainty around the predicted NOAEL in humans. Thus, this standard deviation represented by the GSD of 2.5-2.6 is probably due to potential differences in biological sensitivity between species, but includes intraspecies differences.
AF for the quality of the whole database:
1
Justification:
Reliable studies used.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

In deriving the DNELs for hazard identification for inhalation, dermal route and oral exposure mostly ECHA's guidance is used, which is generally conservative by using default values in absence of data outside the requirements of REACH regulation Annex VII to Annex XI. In addition, the used assessment factors used have been adequately documented. For inter and intraspecies assessment factors have been used which were conducted to be scientifically sound by ECETOC (TR 110, 2010) and which are based on a thorough review of the scientific literature. Therefore the DNELs for all human health endpoints relevant for the general population are considered sufficiently conservative to be used in risk characterization.