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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
0.82 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
61.71 mg/m³
Explanation for the modification of the dose descriptor starting point:

As no long-term study on inhalation is available, route-to-route extrapolation has been performed. Data generated with the related substance DEAPA was used to cover the higher tier toxicity endpoints. The NOAEL observed in the prenatal development study in rat of 50 mg/kg bw/d was used to derive a DNEL long-term, systemic effects via the inhalation route. For the route-to-route extrapolation from oral to inhalation, the dose descriptor starting point = 61.71 mg/m³ (50 mg/kg bw/d x 1/(0.38 m³/kg bw/d) x 6.7 m³/10 m³ x 0.5 x 7/5). The oral dose for rats was converted to the corresponding air concentration using a standard breathing volume for the rat (0.38 m³/kg for 8 hours exposure of workers). For workers the resulting air concentration needs to be additionally corrected for the difference between basal caloric demand and caloric demand under light activity. This correction factor is derived from the inhaled volumes in 8 hours under the respective conditions (6.7 m³ for base level, 10 m³ for light activity). In addition, the NOAEL needed to be divided by 2 as the bioavailability via the inhalation route is considered as 100%, while for oral exposure this is only 50%). A correction factor 7/5 for difference in exposure duration and frequency was added (7 days/week dosing in the animal study, 5 days / week exposure of the workers).


No long term toxicity studies are available for the test substance. Data from a read-across oral prenatal development study with the structurally related substance DEAPA could be used as starting point for extrapolation to the dermal route.


A prenatal development toxicity study in rats was performed according to OECD 414, via oral gavage at dose levels 0, 50, 250 and 750 mg/kg bw/day. The potential toxic effects of DEAPA on the pregnant female rats and on embryonic and fetal development was evaluated and the study reports multiple treatment related effects, observed in the early treatment days of the animals, that have an impact on maternal animals and fetus' chances of survival. At 250 mg/kg bw/d, test item-related clinical signs observed on maternal animals consisted of round back, emaciated appearance, piloerection, loud breathing, and/or reddish vaginal discharge. These clinical signs had dose-related increased incidence and were adverse. Other effects observed at 250 mg/kg bw/d included slightly lower mean gravid uterus weight, higher mean post-implantation loss , lower mean number of live fetuses, litter losses by resorption. Since the developmental toxicity study shows that the test item has an impact on fetus survival, it is recommended to choose a conservative approach, with NOAEL at 50 mg/kg bw/d.

AF for dose response relationship:
1
Justification:
NOAEL is used as starting point; no additional assessment factor required
AF for differences in duration of exposure:
6
Justification:
Difference in duration, subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Covered by calculation for route-to-route extrapolation
AF for other interspecies differences:
2.5
Justification:
default assessment factor
AF for intraspecies differences:
5
Justification:
worker population
AF for the quality of the whole database:
1
Justification:
default assessment factor
AF for remaining uncertainties:
1
Justification:
default assessment factor
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.23 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
70 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No long term toxicity studies are available for the test substance. Data from a read-across oral preclinical development toxicity study with the structurally related substance DEAPA could be used as starting point for extrapolation to the dermal route.


A prenatal development toxicity study in rats was performed according to OECD 414, via oral gavage at dose levels 0, 50, 250 and 750 mg/kg bw/day. The potential toxic effects of DEAPA on the pregnant female rats and on embryonic and fetal development was evaluated and the study reports multiple treatment related effects, observed in the early treatment days of the animals, that have an impact on maternal animals and fetus' chances of survival. At 250 mg/kg bw/d, test item-related clinical signs observed on maternal animals consisted of round back, emaciated appearance, piloerection, loud breathing, and/or reddish vaginal discharge. These clinical signs had dose-related increased incidence and were adverse. Other effects observed at 250 mg/kg bw/d included slightly lower mean gravid uterus weight, higher mean post-implantation loss , lower mean number of live fetuses, litter losses by resorption. Since the developmental toxicity study shows that the test item has an impact on fetus survival, it is recommended to choose a conservative approach, with NOAEL at 50 mg/kg bw/d.


For route-to-route extrapolation (oral to dermal), no default factor (i.e. factor 1) should be applied as part of the overall assessment factor, as it is assumed that dermal absorption will not be higher than oral absorption. A correction factor of 7/5 is applied to correct for difference in exposure duration and frequency (7 days / week for the animal study, 5 days/week for the workers).

AF for dose response relationship:
1
Justification:
NOAEL is used as starting point; no additional assessment factor is required.
AF for differences in duration of exposure:
6
Justification:
Difference in duration, subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
from rat to human
AF for other interspecies differences:
2.5
Justification:
default assessment factor
AF for intraspecies differences:
5
Justification:
worker population
AF for the quality of the whole database:
1
Justification:
default assessment factor
AF for remaining uncertainties:
1
Justification:
default assessment factor
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.434 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
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:
21.7 mg/m³
Explanation for the modification of the dose descriptor starting point:

As no long-term study on inhalation is available, route-to-route extrapolation has been performed. Data generated with the related substance DEAPA was used to cover the higher tier toxicity endpoints. The NOAEL observed in the prenatal development study in rat of 50 mg/kg bw was used to derive a DNEL long-term, systemic effects via the inhalation route. For the route-to-route extrapolation from oral to inhalation, the dose descriptor starting point = 21.7 mg/m³ (50 mg/kg bw/d x 1/(1.15 m³/kg bw/d) x 50%/100%). The NOAEL needed to be divided by 2 as the bioavailability via the inhalation route is considered as 100%, while for oral exposure this is only 50%). No long term toxicity studies are available for the test substance. Data from a read-across oral prenatal development study with the structurally related substance DEAPA could be used as starting point for extrapolation to the inhalation route route. A prenatal development toxicity study in rats was performed according to OECD 414, via oral gavage at dose levels 0, 50, 250 and 750 mg/kg bw/day. The potential toxic effects of DEAPA on the pregnant female rats and on embryonic and fetal development was evaluated and the study reports multiple treatment related effects, observed in the early treatment days of the animals, that have an impact on maternal animals and fetus' chances of survival. At 250 mg/kg bw/d, test item-related clinical signs observed on maternal animals consisted of round back, emaciated appearance, piloerection, loud breathing, and/or reddish vaginal discharge. These clinical signs had dose-related increased incidence and were adverse. Other effects observed at 250 mg/kg bw/d included slightly lower mean gravid uterus weight, higher mean post-implantation loss , lower mean number of live fetuses, litter losses by resorption. Since the developmental toxicity study shows that the test item has an impact on fetus survival, it is recommended to choose a conservative approach, with NOAEL at 50 mg/kg bw/d.

AF for dose response relationship:
1
Justification:
NOAEL is used as starting point; no additional assessment factor required
AF for differences in duration of exposure:
2
Justification:
difference in duration, sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
is included in the route-to-route extrapolation
AF for other interspecies differences:
2.5
Justification:
default assessment factor
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
Justification:
default assessment factor
AF for remaining uncertainties:
1
Justification:
default assessment factor
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
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:
developmental toxicity / teratogenicity
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
Explanation for the modification of the dose descriptor starting point:

No long term toxicity studies are available for the test substance. Data from a read-across oral preclinical development toxicity study with the structurally related substance DEAPA could be used as starting point for extrapolation to the dermal route.


A prenatal development toxicity study in rats was performed according to OECD 414, via oral gavage at dose levels 0, 50, 250 and 750 mg/kg bw/day. The potential toxic effects of DEAPA on the pregnant female rats and on embryonic and fetal development was evaluated and the study reports multiple treatment related effects, observed in the early treatment days of the animals, that have an impact on maternal animals and fetus' chances of survival. At 250 mg/kg bw/d, test item-related clinical signs observed on maternal animals consisted of round back, emaciated appearance, piloerection, loud breathing, and/or reddish vaginal discharge. These clinical signs had dose-related increased incidence and were adverse. Other effects observed at 250 mg/kg bw/d included slightly lower mean gravid uterus weight, higher mean post-implantation loss , lower mean number of live fetuses, litter losses by resorption. Since the developmental toxicity study shows that the test item has an impact on fetus survival, it is recommended to choose a conservative approach, with NOAEL at 50 mg/kg bw/d.


For route-to-route extrapolation (oral to dermal), no default factor (i.e. factor 1) should be applied as part of the overall assessment factor, as it is assumed that dermal absorption will not be higher than oral absorption.

AF for dose response relationship:
1
Justification:
NOAEL is used as starting point; no additional assessment factor is required.
AF for differences in duration of exposure:
2
Justification:
Difference in duration, sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
from rat to human
AF for other interspecies differences:
2.5
Justification:
default assessment factor
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
Justification:
default assessment factor
AF for remaining uncertainties:
1
Justification:
default assessment factor
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

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:
developmental toxicity / teratogenicity
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
Explanation for the modification of the dose descriptor starting point:

No long term toxicity studies are available for the test substance. Data from a read-across oral preclinical development toxicity study with the structurally related substance DEAPA could be used as starting point for extrapolation to the oral route.


A prenatal development toxicity study in rats was performed according to OECD 414, via oral gavage at dose levels 0, 50, 250 and 750 mg/kg bw/day. The potential toxic effects of DEAPA on the pregnant female rats and on embryonic and fetal development was evaluated and the study reports multiple treatment related effects, observed in the early treatment days of the animals, that have an impact on maternal animals and fetus' chances of survival. At 250 mg/kg bw/d, test item-related clinical signs observed on maternal animals consisted of round back, emaciated appearance, piloerection, loud breathing, and/or reddish vaginal discharge. These clinical signs had dose-related increased incidence and were adverse. Other effects observed at 250 mg/kg bw/d included slightly lower mean gravid uterus weight, higher mean post-implantation loss , lower mean number of live fetuses, litter losses by resorption. Since the developmental toxicity study shows that the test item has an impact on fetus survival, it is recommended to choose a conservative approach, with NOAEL at 50 mg/kg bw/d.


 

AF for dose response relationship:
1
Justification:
NOAEL is used as starting point; no additional assessment factor is required.
AF for differences in duration of exposure:
2
Justification:
Difference in duration, sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
from rat to human
AF for other interspecies differences:
2.5
Justification:
default assessment factor
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
Justification:
default assessment factor
AF for remaining uncertainties:
1
Justification:
default assessment factor
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