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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
0.31 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):
50
Dose descriptor starting point:
other: LOAEL in F0 generation of OECD 443, NOAEL in F1 adult generation of OECD 443
Value:
18 mg/kg bw/day
Value:
15.5 mg/m³
Explanation for the modification of the dose descriptor starting point:




















Step 1) Relevant dose-descriptor



LOAEL/NOAEL: 18 mg/kg bw/day



as determined in OECD 443 study in rats (based on increased ALP and decreased albumin in F1 animals)



Step 2) Modification of starting point



39%/80%


 


0.38 m3/kg bw


 


6.7 m3/10 m3


 



Ratio of oral to inhalation absorption


 


Respiratory volume of a rat, corrected for 8 h exposure


 


Correction for activity driven differences of respiratory volumes in workers compared to workers in rest



Modified dose-descriptor



NOAEC corrected = 18 * (39/80) * (1/0.38) * (6.7/10) = 15.5 mg/m3



 



for details on absorption estimation, please refer to IUCLID section 7.1 (toxicokinetics)


AF for dose response relationship:
2
Justification:
point of departure for DNEL derivation was LOAEL in F0 generation of OECD 443 and NOAEL in adult F1 rats of same study. The effects in the F0 generation were limited and weak, therefore an assessment factor of 2 was chosen since the POD did not correspond to a NOAEL in all animals, but only very mild toxicity was observed in some of the animals.
AF for differences in duration of exposure:
2
Justification:
Treatment period was 17-19 weeks in OECD 443 for F0 generation and 18 weeks in OECD 443 for F1 generation. This is very closely corresponding to the 12 weeks standard exposure time of a subchronic toxicity study (OECD 408), for which a factor of 2 is the recommended assessment factor for duration of exposure in ECHA guidance R.8.
AF for interspecies differences (allometric scaling):
1
Justification:
not required (according to ECHA guidance document R.8)
AF for other interspecies differences:
2.5
Justification:
default factor for interspecies differences (according to ECHA guidance document R.8)
AF for intraspecies differences:
5
Justification:
default factor for intraspecies differences (according to ECHA guidance document R.8)
AF for the quality of the whole database:
1
Justification:
GLP and Guideline study
AF for remaining uncertainties:
1
Justification:
covered by interspecies factor
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:
0.44 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):
200
Dose descriptor starting point:
other: LOAEL in F0 generation of OECD 443, NOAEL in F1 adult generation of OECD 443
Value:
18 mg/kg bw/day
Value:
87.75 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:




















Step 1) Relevant dose-descriptor



LOAEL/NOAEL: 18 mg/kg bw/day



as determined in OECD 443 study in rats (based on increased ALP and decreased albumin in F1 animals)



Step 2) Modification of starting point



39%/8%


 


 



Ratio of oral to dermal absorption



Modified dose-descriptor



NOAEC corrected = 18 * (39/8) = 87.75 mg/kg bw/d



 



for details on absorption estimation, please refer to IUCLID section 7.1 (toxicokinetics)


AF for dose response relationship:
2
Justification:
point of departure for DNEL derivation was LOAEL in F0 generation of OECD 443 and NOAEL in adult F1 rats of same study. The effects in the F0 generation were limited and weak, therefore an assessment factor of 2 was chosen since the POD did not correspond to a NOAEL in all animals, but only very mild toxicity was observed in some of the animals.
AF for differences in duration of exposure:
2
Justification:
Treatment period was 17-19 weeks in OECD 443 for F0 generation and 18 weeks in OECD 443 for F1 generation. This is very closely corresponding to the 12 weeks standard exposure time of a subchronic toxicity study (OECD 408), for which a factor of 2 is the recommended assessment factor for duration of exposure in ECHA guidance R.8.
AF for interspecies differences (allometric scaling):
4
Justification:
default (according to ECHA Guidance R.8)
AF for other interspecies differences:
2.5
Justification:
default factor for interspecies differences (according to ECHA guidance document R.8)
AF for intraspecies differences:
5
Justification:
default factor for intraspecies differences (according to ECHA guidance document R.8)
AF for the quality of the whole database:
1
Justification:
Guideline and GLP study
AF for remaining uncertainties:
1
Justification:
not 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

DNEL inhalation, long-term, systemic (worker):








































































Description



Value



Remark



Step 1) Relevant dose-descriptor



LOAEL/NOAEL: 18 mg/kg bw/day



as determined in OECD 443 study in rats (based on increased ALP and decreased albumin in F1 animals)



Step 2) Modification of starting point



39%/80%


 


0.38 m3/kg bw


 


6.7 m3/10 m3


 



Ratio of oral to inhalation absorption


 


Respiratory volume of a rat, corrected for 8 h exposure


 


Correction for activity driven differences of respiratory volumes in workers compared to workers in rest



Modified dose-descriptor



NOAEC corrected = 18 * (39/80) * (1/0.38) * (6.7/10) = 15.5 mg/m3



 



Step 3) Assessment factors



 



 



Allometric scaling



1



not required (according to ECHA guidance document R.8)



Remaining differences



2.5



accounting for interspecies differences (according to ECHA guidance document R.8)



Intraspecies



5



Accounting for differences in worker population



Exposure duration



2



OECD 443 with 18 weeks treatment as starting point



Dose response



2



LOAEL in F0 parental animals is used as starting point, but is considered NOAEL in F1 adult rats



Quality of database



1



Guideline and GLP study



DNEL



Value



 



 



15.5 / (1 x 2.5 x 5 x 2 x 2 x 1) = 0.31 mg/m3



 



 


 


DNEL dermal, long-term, systemic (worker):








































































Description



Value



Remark



Step 1) Relevant dose-descriptor



LOAEL/NOAEL: 18 mg/kg bw/day



as determined in OECD 443 study in rats (based on increased ALP and decreased albumin in F1 animals)



Step 2) Modification of starting point



39%/8%


 


 



Ratio of oral to dermal absorption



Modified dose-descriptor



NOAEC corrected = 18 * (39/8) = 87.75 mg/kg bw/d



 



Step 3) Assessment factors



 



 



Allometric scaling



4



Default allometric scaling factor for rat to human (according to ECHA guidance document R.8)



Remaining differences



2.5



accounting for interspecies differences (according to ECHA guidance document R.8)



Intraspecies



5



Accounting for differences in worker population



Exposure duration



2



OECD 443 with 18 weeks treatment as starting point



Dose response



2



LOAEL in F0 parental animals is used as starting point, but is considered NOAEL in F1 adult rats



Quality of database



1



Guideline and GLP study



DNEL



Value



 



 



87.75 / (4 x 2.5 x 5 x 2 x 2 x 1) = 0.44 mg/kg bw/d



 




 


 


General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.08 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):
100
Dose descriptor starting point:
other: LOAEL in F0 generation of OECD 443, NOAEL in F1 adult generation of OECD 443
Value:
18 mg/kg bw/day
Value:
7.63 mg/m³
Explanation for the modification of the dose descriptor starting point:




















Step 1) Relevant dose-descriptor



LOAEL/NOAEL: 18 mg/kg bw/day



as determined in OECD 443 study in rats (based on increased ALP and decreased albumin in F1 animals)



Step 2) Modification of starting point



39%/80%


 


1.15 m3/kg bw



Ratio of oral to inhalation absorption (default according to ECHA guidance R.8)


Respiratory volume of a rat, corrected for 24 h exposure



Modified dose-descriptor



NOAEC corrected = 18 * (39/80) * (1/1.15) = 7.63 mg/m3



 



for details on absorption estimation, please refer to IUCLID section 7.1 (toxicokinetics)


AF for dose response relationship:
2
Justification:
point of departure for DNEL derivation was LOAEL in F0 generation of OECD 443 and NOAEL in adult F1 rats of same study. The effects in the F0 generation were limited and weak, therefore an assessment factor of 2 was chosen since the POD did not correspond to a NOAEL in all animals, but only very mild toxicity was observed in some of the animals.
AF for differences in duration of exposure:
2
Justification:
Treatment period was 17-19 weeks in OECD 443 for F0 generation and 18 weeks in OECD 443 for F1 generation. This is very closely corresponding to the 12 weeks standard exposure time of a subchronic toxicity study (OECD 408), for which a factor of 2 is the recommended assessment factor for duration of exposure in ECHA guidance R.8.
AF for interspecies differences (allometric scaling):
1
Justification:
not required (according to ECHA guidance document R.8)
AF for other interspecies differences:
2.5
Justification:
default factor for interspecies differences (according to ECHA guidance document R.8)
AF for intraspecies differences:
10
Justification:
default factor for intraspecies differences (according to ECHA guidance document R.8)
AF for the quality of the whole database:
1
Justification:
Guideline and GLP study
AF for remaining uncertainties:
1
Justification:
not 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:
0.22 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):
400
Dose descriptor starting point:
other: LOAEL in F0 generation of OECD 443, NOAEL in F1 adult generation of OECD 443
Value:
18 mg/kg bw/day
Value:
87.75 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:




















Step 1) Relevant dose-descriptor



LOAEL/NOAEL: 18 mg/kg bw/day



as determined in OECD 443 study in rats (based on increased ALP and decreased albumin in F1 animals)



Step 2) Modification of starting point



39%/8%



Ratio of oral to dermal absorption



Modified dose-descriptor



NOAEC corrected = 18 * (39/8) = 87.75 mg/kg bw/d



 



for details on absorption estimation, please refer to IUCLID section 7.1 (toxicokinetics)


AF for dose response relationship:
2
Justification:
point of departure for DNEL derivation was LOAEL in F0 generation of OECD 443 and NOAEL in adult F1 rats of same study. The effects in the F0 generation were limited and weak, therefore an assessment factor of 2 was chosen since the POD did not correspond to a NOAEL in all animals, but only very mild toxicity was observed in some of the animals.
AF for differences in duration of exposure:
2
Justification:
Treatment period was 17-19 weeks in OECD 443 for F0 generation and 18 weeks in OECD 443 for F1 generation. This is very closely corresponding to the 12 weeks standard exposure time of a subchronic toxicity study (OECD 408), for which a factor of 2 is the recommended assessment factor for duration of exposure in ECHA guidance R.8.
AF for interspecies differences (allometric scaling):
4
Justification:
default (according to ECHA Guidance R.8)
AF for other interspecies differences:
2.5
Justification:
default factor for interspecies differences (according to ECHA guidance document R.8)
AF for intraspecies differences:
10
Justification:
default factor for intraspecies differences (according to ECHA guidance document R.8)
AF for the quality of the whole database:
1
Justification:
Guideline and GLP study
AF for remaining uncertainties:
1
Justification:
not 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:
0.05 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):
400
Dose descriptor starting point:
other: LOAEL in F0 generation of OECD 443, NOAEL in F1 adult generation of OECD 443
Value:
18 mg/kg bw/day
Value:
18 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:




















Step 1) Relevant dose-descriptor



LOAEL/NOAEL: 18 mg/kg bw/day



as determined in OECD 443 study in rats (based on increased ALP and decreased albumin in F1 animals)



Step 2) Modification of starting point



39%/39%



No differences in oral absorption expected between rats and humans


Substance was administered in feed



Modified dose-descriptor



NOAEC corrected = 18 * (39/39) = 18 mg/kg bw/d



 



for details on absorption estimation, please refer to IUCLID section 7.1 (toxicokinetics)


AF for dose response relationship:
2
Justification:
point of departure for DNEL derivation was LOAEL in F0 generation of OECD 443 and NOAEL in adult F1 rats of same study. The effects in the F0 generation were limited and weak, therefore an assessment factor of 2 was chosen since the POD did not correspond to a NOAEL in all animals, but only very mild toxicity was observed in some of the animals.
AF for differences in duration of exposure:
2
Justification:
Treatment period was 17-19 weeks in OECD 443 for F0 generation and 18 weeks in OECD 443 for F1 generation. This is very closely corresponding to the 12 weeks standard exposure time of a subchronic toxicity study (OECD 408), for which a factor of 2 is the recommended assessment factor for duration of exposure in ECHA guidance R.8.
AF for interspecies differences (allometric scaling):
4
Justification:
default (according to ECHA Guidance R.8)
AF for other interspecies differences:
2.5
Justification:
default (according to ECHA Guidance R.8)
AF for intraspecies differences:
10
Justification:
default (according to ECHA Guidance R.8)
AF for the quality of the whole database:
1
Justification:
Guideline and GLP study
AF for remaining uncertainties:
1
Justification:
not 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

DNEL inhalation, long-term, systemic (general population):








































































Description



Value



Remark



Step 1) Relevant dose-descriptor



LOAEL/NOAEL: 18 mg/kg bw/day



as determined in OECD 443 study in rats (based on increased ALP and decreased albumin in F1 animals)



Step 2) Modification of starting point



39%/80%


 


1.15 m3/kg bw



Ratio of oral to inhalation absorption (default according to ECHA guidance R.8)


Respiratory volume of a rat, corrected for 24 h exposure



Modified dose-descriptor



NOAEC corrected = 18 * (39/80) * (1/1.15) = 7.63 mg/m3



 



Step 3) Assessment factors



 



 



Allometric scaling



1



not required (according to ECHA guidance document R.8)



Remaining differences



2.5



accounting for interspecies differences (according to ECHA guidance document R.8)



Intraspecies



10



Accounting for differences in general population



Exposure duration



2



OECD 443 with 18 weeks treatment as starting point



Dose response



2



LOAEL in F0 parental animals is used as starting point, but is considered NOAEL in F1 adult rats



Quality of database



1



Guideline and GLP study



DNEL



Value



 



 



7.63 / (1 x 2.5 x 10 x 2 x 2 x 1) = 0.08 mg/m3



 



 


DNEL dermal, long-term, systemic (general population):








































































Description



Value



Remark



Step 1) Relevant dose-descriptor



LOAEL/NOAEL: 18 mg/kg bw/day



as determined in OECD 443 study in rats (based on increased ALP and decreased albumin in F1 animals)



Step 2) Modification of starting point



39%/8%



Ratio of oral to dermal absorption



Modified dose-descriptor



NOAEC corrected = 18 * (39/8) = 87.75 mg/kg bw/d



 



Step 3) Assessment factors



 



 



Allometric scaling



4



Default allometric scaling factor for rat to human (according to ECHA guidance document R.8)



Remaining differences



2.5



accounting for interspecies differences (according to ECHA guidance document R.8)



Intraspecies



10



Accounting for differences in general population



Exposure duration



2



OECD 443 with 18 weeks treatment as starting point



Dose response



2



LOAEL in F0 parental animals is used as starting point, but is considered NOAEL in F1 adult rats



Quality of database



1



Guideline and GLP study



DNEL



Value



 



 



87.75 / (4 x 2.5 x 10 x 2 x 2 x 1) = 0.22 mg/kg bw/d



 



 


DNEL oral, long-term, systemic (general population):








































































Description



Value



Remark



Step 1) Relevant dose-descriptor



LOAEL/NOAEL: 18 mg/kg bw/day



as determined in OECD 443 study in rats (based on increased ALP and decreased albumin in F1 animals)



Step 2) Modification of starting point



39%/39%



No differences in oral absorption expected between rats and humans


Substance was administered in feed



Modified dose-descriptor



NOAEC corrected = 18 * (39/39) = 18 mg/kg bw/d



 



Step 3) Assessment factors



 



 



Allometric scaling



4



Default allometric scaling factor for rat to human (according to ECHA guidance document R.8)



Remaining differences



2.5



accounting for interspecies differences (according to ECHA guidance document R.8)



Intraspecies



10



Accounting for differences in general population



Exposure duration



2



OECD 443 with 18 weeks treatment as starting point



Dose response



2



LOAEL in F0 parental animals is used as starting point, but is considered NOAEL in F1 adult rats



Quality of database



1



Guideline and GLP study



DNEL



Value



 



 



18 / (4 x 2.5 x 10 x 2 x 2 x 1) = 0.05 mg/kg bw/d