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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12.5
Dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
61.25 mg/m³
Explanation for the modification of the dose descriptor starting point:

No long-term exposure data are available for the inhalation route, therefore the NOAEL identified in an in vivo chronic study where the substance was given in feed.

Route-to-route extrapolation is needed from the oral to the inhalation route:

The NOAEL rat is converted to NOAEL human by dividing with the allometric scaling factor 4 for interspecies differences. By multiplying the NOAEL human with the default human body weight (70 kg) and dividing the default human breathing volume referring to workers (10 m3 in 8h and light activity), this dose is then translated into an air concentration. The absorption rate for human via inhalation is not known for the substance.

NOAEL oral= 50 mg/kg b.w.

Standard human body weight = 70 kg.

Default human breathing volume for workers in 8 hours (light activity) = 10 m3.

Due to the difference between human (workers) and experimental exposure conditions, a correction factor of 1.4 is applied. Furthermore, a correction factor of 0.5 is used due to differences in bioavailability.

Resulting NOAEC Inhalation = (50/4)* (70/10)* (1.4*0.5) = 61.25 mg/m3.

AF for dose response relationship:
1
Justification:
The starting point for the DNEL derivation is a NOAEL; default factor is 1.
AF for differences in duration of exposure:
1
Justification:
For the extrapolation of the DNEL, a chronic study with a reproductive/developmental phase is used which includes exposure to the test chemical throughout the post-fertilisation pre-implantation phase, the entire period of gestation (including both organogenesis and foetal growth phases), parturition, and the first period of postnatal life. Therefore, assessment factor for exposure duration is not to be used (Guidance on Assessment Factors
to Derive a DNEL, Technical Report No. 110, 2010).
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scalling is already taken into consideration during the route-to-route extrapolation.
AF for other interspecies differences:
2.5
Justification:
Default factor of 2.5 is applied for other interspecies differences (toxicokinetic differences not related to metabolic rate and toxicodynamic differences).
AF for intraspecies differences:
5
Justification:
Default factor for workers is applied.
AF for the quality of the whole database:
1
Justification:
Standard quality of database.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
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:
14 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):
50
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 exposure data are available for the dermal route for the substance. Therefore, the NOAEL obtained from a chronic study on rats where the substance was administered via the oral route is used. No route-to-route extrapolation is needed as it is assumed that dermal absorption will not be higher than oral absorption; default factor is 1.

Due to the difference between human (workers) and experimental exposure conditions, a correction factor of 1.4 is applied.

The modified NOAEL is 50 mg/kg bw/day * 1.4 = 70 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
The starting point for the DNEL derivation is a NOAEL; default factor is 1.
AF for differences in duration of exposure:
1
Justification:
For the extrapolation of the DNEL, a chronic study with a reproductive/developmental phase is used which includes exposure to the test chemical throughout the post-fertilisation pre-implantation phase, the entire period of gestation (including both organogenesis and foetal growth phases), parturition, and the first period of postnatal life. Therefore, assessment factor for exposure duration is not to be used (Guidance on Assessment Factors to Derive a DNEL, Technical Report No. 110, 2010).
AF for interspecies differences (allometric scaling):
4
Justification:
Extrapolation from rats to humans
AF for other interspecies differences:
2.5
Justification:
Default factor of 2.5 is applied for other interspecies differences (toxicokinetic differences not related to metabolic rate and toxicodynamic differences).
AF for intraspecies differences:
5
Justification:
Default factor for workers is applied.
AF for the quality of the whole database:
1
Justification:
Standard quality of database.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

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:
0.88 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):
25
Dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
21.88 mg/m³
Explanation for the modification of the dose descriptor starting point:

No long-term exposure data are available for the substance via the inhalation route. Therefore, the NOAEL obtained from a chronic toxicity study on rats via the oral route was used and route-to-route extrapolation is needed.

The NOAEL rat is divided by the allometric scaling factor 4 for interspecies differences, thus obtaining the NOAEL human. The NOAEL human is then multiplied by the default human body weight (70 kg) and divided by the default human breathing volume for general population (20 m3 in 24 hours and basal caloric demand). The absorption rate for human via inhalation is not known for the substance and a correction factor of 0.5 is used due to differences in bioavailability.

NOAEL oral = 50 mg/kg bw/day

Standard human body weight = 70 kg

Default human breathing volume for general pobulation in 24 hours = 20 m3

Allometric scalling factor for rats as compared to humans = 4

Correction factor for differences in bioavalilability = 0.5

NOAEC Inhalation = (50/4)* (70/20)* 0.5 = 21.88 mg/m3.

AF for dose response relationship:
1
Justification:
The starting point for the DNEL derivation is a NOAEL; default factor is 1.
AF for differences in duration of exposure:
1
Justification:
For the extrapolation of the DNEL, a chronic study with a reproductive/developmental phase is used which includes exposure to the test chemical throughout the post-fertilisation pre-implantation phase, the entire period of gestation (including both organogenesis and foetal growth phases), parturition, and the first period of postnatal life. Therefore, assessment factor for exposure duration is not to be used (Guidance on Assessment Factors
to Derive a DNEL, Technical Report No. 110, 2010).
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scalling is already taken into consideration during the route-to-route extrapolation.
AF for other interspecies differences:
2.5
Justification:
Default factor of 2.5 is applied for other interspecies differences (toxicokinetic differences not related to metabolic rate and toxicodynamic differences).
AF for intraspecies differences:
10
Justification:
Default factor for general population is applied.
AF for the quality of the whole database:
1
Justification:
Standard quality of database.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
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:
5 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):
100
Dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No long-term exposure data are available for the dermal route for the substance. Therefore, the NOAEL obtained from a chronic study on rats where the substance was administered via the oral route is used. No route-to-route extrapolation is needed as it is assumed that dermal absorption will not be higher than oral absorption; default factor is 1.

AF for dose response relationship:
1
Justification:
The starting point for the DNEL derivation is a NOAEL; default factor is 1.
AF for differences in duration of exposure:
1
Justification:
For the extrapolation of the DNEL, a chronic study with a reproductive/developmental phase is used which includes exposure to the test chemical throughout the post-fertilisation pre-implantation phase, the entire period of gestation (including both organogenesis and foetal growth phases), parturition, and the first period of postnatal life. Therefore, assessment factor for exposure duration is not to be used (Guidance on Assessment Factors
to Derive a DNEL, Technical Report No. 110, 2010).
AF for interspecies differences (allometric scaling):
4
Justification:
Extrapolation from rats to humans.
AF for other interspecies differences:
2.5
Justification:
Default factor of 2.5 is applied for other interspecies differences (toxicokinetic differences not related to metabolic rate and toxicodynamic differences).
AF for intraspecies differences:
10
Justification:
Default value for general population
AF for the quality of the whole database:
1
Justification:
Standard quality of database
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

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:
developmental toxicity / teratogenicity
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
AF for dose response relationship:
1
Justification:
The starting point for the DNEL derivation is a NOAEL; default factor is 1.
AF for differences in duration of exposure:
1
Justification:
For the extrapolation of the DNEL, a chronic study with a reproductive/developmental phase is used which includes exposure to the test chemical throughout the post-fertilisation pre-implantation phase, the entire period of gestation (including both organogenesis and foetal growth phases), parturition, and the first period of postnatal life. Therefore, assessment factor for exposure duration is not to be used (Guidance on Assessment Factors
to Derive a DNEL, Technical Report No. 110, 2010).
AF for interspecies differences (allometric scaling):
4
Justification:
Extrapolation from rats to humans.
AF for other interspecies differences:
2.5
Justification:
Default factor of 2.5 is applied for other interspecies differences (toxicokinetic differences not related to metabolic rate and toxicodynamic differences).
AF for intraspecies differences:
10
Justification:
Default factor for general population is applied.
AF for the quality of the whole database:
1
Justification:
Standard quality of database.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population