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Workers - Hazard via inhalation route

Systemic effects

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

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
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 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
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low 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:
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:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
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:
0.25 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 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:
defaults
AF for intraspecies differences:
10
Justification:
consumers
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
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 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
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
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