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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
4.9 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):
50
Dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
246.8 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 200 mg/kg bw/day in a 90-day repeated dose toxicity study in rat.


An additional factor of 1.4 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.



Corrected NOAEL(inhalation) = NOAEL(oral, rat) x 1/sRVratxABS(oral-rat)/ABS(inh-human)  x sRVhuman/wRV x 1.4
           = 200 mg/kg x 1/0.38 m3/kg/d x 50%/100% x 6.7 m3/10 m3 x 1.4 = 246.8 mg/m3


with sRV: standard respiratory volume (8h); ABS: Absorption; wRV: worker respiratory volume


ABSoral /ABSinhal= 50%/100%= 0.5

AF for dose response relationship:
1
Justification:
Value is NOAEL
AF for differences in duration of exposure:
2
Justification:
extrapolation from sub-chronic study to chronic exposure
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:
Factor to correct for toxicokinetic differences not related to metabolic
rate (small part) and toxicodynamic differences (larger part). No substance-specific information is available to address this aspect more specifically.
AF for intraspecies differences:
5
Justification:
Difference in sensitivity among workers
AF for the quality of the whole database:
1
Justification:
Reliable studies used
AF for remaining uncertainties:
2
Justification:
Factor to account for the use of substance-tailored exposure based waiving as required by Annex XI 3.2
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:
294.1 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):
200
Dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
58 823 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

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


Correction dermal NOAEL: 200 mg/kg bw/day x 50/0.17a = 58,824 mg/kg bw/day


(a % oral/dermal absorption)

AF for dose response relationship:
1
Justification:
Value is NOAEL
AF for differences in duration of exposure:
2
Justification:
extrapolation from subchronic study to chronic exposure worker
AF for interspecies differences (allometric scaling):
4
Justification:
Correction for caloric demand from rat to human
AF for other interspecies differences:
2.5
Justification:
Factor to correct for toxicokinetic differences not related to metabolic
rate (small part) and toxicodynamic differences (larger part). No substance-specific information is available to address this aspect more specifically.
AF for intraspecies differences:
5
Justification:
Difference in sensitivity among workers
AF for the quality of the whole database:
1
Justification:
Reliable data used
AF for remaining uncertainties:
2
Justification:
Factor to account for the use of substance-tailored exposure based waiving as required by Annex XI 3.2
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

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):
100
Dose descriptor starting point:
NOAEL
Value:
200 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
87 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


 


            = 200 mg/kg bw/day * 1/1.15 m3/kg * ABSoral-rat /ABSinhal-human


 


            = 200 mg/kg bw/day * 1/1.15 m3/kg  * 0.5 =  87.0 mg/m3


 


With ABS: Absorption, sRV: Standard Respiratory Volume;


ABSoral /ABSinhal= 50/100= 0.5

AF for dose response relationship:
1
Justification:
Value is NOAEL
AF for differences in duration of exposure:
2
Justification:
extrapolation from sub-chronic study to chronic exposure
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:
Factor to correct for toxicokinetic differences not related to metabolic
rate (small part) and toxicodynamic differences (larger part). No substance-specific information is available to address this aspect more specifically.
AF for intraspecies differences:
10
Justification:
Difference in sensitivity within general population
AF for the quality of the whole database:
1
Justification:
Reliable data used
AF for remaining uncertainties:
2
Justification:
Factor to account for the use of substance-tailored exposure based waiving as required by Annex XI 3.2
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:
147.1 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):
400
Dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
58 824 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Kinetics (metabolism, distribution and excretion) are considered to be similar for oral and dermal intake in the absence of evidence of the opposite.
Correction dermal NOAEL: 200 mg/kg bw/day x 50/0.17a = 58,824 mg/kg bw/day
(a % oral/dermal absorption)

AF for dose response relationship:
1
Justification:
Value is NOAEL
AF for differences in duration of exposure:
2
Justification:
extrapolation from subchronic study to chronic exposure worker
AF for interspecies differences (allometric scaling):
4
Justification:
Correction for caloric demand from rat to human
AF for other interspecies differences:
2.5
Justification:
Factor to correct for toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part). No substance-specific information is available to address this aspect more specifically.
AF for intraspecies differences:
10
Justification:
Difference in sensitivity within the human population
AF for the quality of the whole database:
1
Justification:
Reliable data used
AF for remaining uncertainties:
2
Justification:
Factor to account for the use of substance-tailored exposure based waiving as required by Annex XI 3.2
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:
0.5 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):
400
Dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No modification needed, repeated dose study via the oral route is available.

AF for dose response relationship:
1
Justification:
Value is NOAEL
AF for differences in duration of exposure:
2
Justification:
extrapolation from subchronic study to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Correction for caloric demand from rat to human
AF for other interspecies differences:
2.5
Justification:
Factor to correct for toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part). No substance-specific information is available to address this aspect more specifically.
AF for intraspecies differences:
10
Justification:
Difference in sensitivity among general population

AF for the quality of the whole database:
1
Justification:
No remaining differences
AF for remaining uncertainties:
2
Justification:
Factor to account for the use of substance-tailored exposure based waiving as required by Annex XI 3.2
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