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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
4.92 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):
25
Dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
123 mg/m³
Explanation for the modification of the dose descriptor starting point:

Kinetics (metabolism, distribution and excretion) are considered to be similar for oral and inhalation intake in the absence of evidence of the opposite.


Starting point:


NOAEL of 50 mg/kg bw/day in a repeated dose toxicity study in rat.


An additional factor was included in the modification calculation to take into account correction for differences between human and experimental exposure conditions. When correcting an oral NOAEL to inhalation NOAEC the correction factor for worker population would be: 7 day/week (experimental animal exposure, check study) / 5 days/week (worker exposure conditions) = 1.4.


 


Conversion of an oral NOAEL into a corrected NOAEC:


For workers (8h exposure/day), the corrected inhalatory NOAEC = oral NOAEL * 1/sRVrat * ABSoral-rat /ABSinhal-human * sRVhuman/wRV


= 50 mg/kg bw/day * 1/0.38 m3/kg/8h * ABSoral-rat /ABSinhal-human * 6.7 m3 (8h)/10 m3 (8h) *1.4


= 50 mg/kg bw/day * 1/0.38 m3/kg/8h * 1 * 6.7 m3 (8h)/10 m3 (8h) *1.4


= 50 /0.38 * 1* (6.7/10) *1.4 = 123 mg/m3.

AF for dose response relationship:
1
Justification:
Value is a NOAEL
AF for differences in duration of exposure:
2
Justification:
semi-chronic studies (EOGRTS and 90-day toxicity)
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:
2.5
Justification:
default
AF for intraspecies differences:
5
Justification:
worker exposure
AF for the quality of the whole database:
1
Justification:
reliable studies used
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.5 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):
100
Dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Route to route extrapolation based on low absorption via the oral route (mainly absorption of hydrolysis products) and low dermal absorption based on physico-chemical properties. Both absorption rates are set at 10% (default).


The NOAEL is based on a weight of evidence approach taking into account the data on repeated dose and reproduction toxicity.

AF for dose response relationship:
1
Justification:
value is a NOAEL
AF for differences in duration of exposure:
2
Justification:
semi-chronic studies (EOGRTS and 90-day toxicity)
AF for interspecies differences (allometric scaling):
4
Justification:
study in rat
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
5
Justification:
worker exposure
AF for the quality of the whole database:
1
Justification:
reliable studies used
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









































































































































Dose mg/kg bw



6.5$



10



50



65$



100



250



350



650$



1000



Dose mg/kg bw



6.5$



10



50



65$



100



250



350



650$



1000



BW



M ↓6%



 



 



M ↓8%



 



M ↓6% (F0)


 



 



M ↓11%


F ↓7%



M ↓5%


M(BWG)


↓11%



Effects on white blood cells



 



 



 



F  WBC↑ ns



WBC↑ >25 %*



 



WBC↑ >35 %*



WBC↑>80%*



WBC↑ >35 %*


(mainly LYMPH)



Lymph nodes histiocytosis/macrophage infiltrate



 



 



(F#)



M+F



M+F



(M+F#)



M+F



M+F



M+F



Kidneys inflammatory cell infiltrate



 



 



 



F



 



M+F (minimal)



M+F ?



F



M+F ?



Liver inflammatory cell infiltrate



 



 



 



 



F



 



M+F



M+F



M+F



Adrenals inflammatory cell infiltrate



 



 



 



 



 



F



 



M+F



 



Study type



90 day diet



OECD 443


Gavage



OECD 443 gavage



90-day diet



OECD 422 gavage



OECD 433 gavage



OECD 422 gavage



90-day diet (once)



OECD 422 Gavage



Study duration



13 wks



10 wks



10 wks



13 wks



Ca 4 wks



10 wks



Ca 4 wks



13 wks



Ca 4 wks



Vehicle



Corn oil



CMC



CMC



Corn oil



Corn oil



CMC



Corn oil



Corn oil



Corn oil



$ females never been pregnant


*effect in females much stronger


# effect in F1, considered non adverse


 


 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.87 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:
NOAEL
Value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
43.5 mg/m³
Explanation for the modification of the dose descriptor starting point:

Kinetics (metabolism, distribution and excretion) are considered to be similar for oral and inhalation intake in the absence of evidence of the opposite.


For the general population (24h exposure/day), the corrected inhalatory NOAEC = oral NOAEL * 1/sRVrat * ABSoral-rat /ABSinhal-human


 


            = 50 mg/kg bw/day * 1/1.15 m3/kg * ABSoral-rat /ABSinhal-human


 


            = 50 mg/kg bw/day * 1/1.15 m3/kg * 1 =  43.5 mg/m3


 


With ABS: Absorption, sRV: Standard Respiratory Volume;


ABSoral-rat /ABSinhal-human= 10/10= 1, assuming no differences in inhalation absorption between rats and humans.

AF for dose response relationship:
1
Justification:
Value is a NOAEL
AF for differences in duration of exposure:
2
Justification:
semi-chronic studies (EOGRTS and 90-day toxicity)
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:
2.5
Justification:
default
AF for intraspecies differences:
10
Justification:
consumers
AF for the quality of the whole database:
1
Justification:
reliable studies used
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.25 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:
NOAEL
Value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Route to route extrapolation based on low absorption via the oral route (mainly absorption of hydrolysis products) and low dermal absorptionbased on physico-chemical properties. Both absorption rates are set at 10% (default).


The NOAEL is based on a weight of evidence approach taking into account the data on repeated dose and reproduction toxicity.

AF for dose response relationship:
1
Justification:
value is a NOAEL
AF for differences in duration of exposure:
2
Justification:
based on sub-chronic studies (EOGRTS and 90-day toxicity)
AF for interspecies differences (allometric scaling):
4
Justification:
study in rat
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
10
Justification:
consumers
AF for the quality of the whole database:
1
Justification:
reliable studies used
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:
0.25 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:
NOAEL
Value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
0.25 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No modification necesary as the critical study is via the oral route

AF for dose response relationship:
1
Justification:
value is a NOAEL
AF for differences in duration of exposure:
2
Justification:
based on sub-chronic studies (EOGRTS and 90-day toxicity)
AF for interspecies differences (allometric scaling):
4
Justification:
study in the rat
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
10
Justification:
consumers
AF for the quality of the whole database:
1
Justification:
reliable studies used
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

see under worker exposure for overview of the studies