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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
16.33 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):
75
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
1 225 mg/m³
Explanation for the modification of the dose descriptor starting point:

No long-term exposure data is available for the inhalation route therefore the NOAEL resulted from an animal study where the substance was orally administered for 29 and 44 -50 days to male and female rats respectively, is used.

Route-to-route extrapolation is therefore 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. It is assumed that absorption rate via inhalation route is similar to absorption rate via oral route.

NOAELoral= 1000 mg/kg b.w

Standard human body weight = 70 kg

Default human breathing volume for workers in 8 hours = 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.

Therefore, NOAECinh= (1000/4)* (70/10)* (1.4*0.5) = 1225 mg/m3

AF for dose response relationship:
1
Justification:
The starting point for the DNEL derivation is a NOAEL; default factor AF=1 is used.
AF for differences in duration of exposure:
6
Justification:
The duration of the animal study is 29 days. Extrapolation needed from subacute to chronic.
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling 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:
Good/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

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:
acute toxicity
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.67 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):
300
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 400 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No long-term exposure data is available for the dermal route therefore the NOAEL resulted from an animal study where the substance was orally administered for 29 days to male rats and 44 -50 days to female rats, is used.

No route-to-route extrapolation needed. 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.

Therefore, the NOAEL = 1000 mg/kg bw/day * 1.4 = 1400 mg/m3

AF for dose response relationship:
1
Justification:
NOAEL was used; default AF is 1.
AF for differences in duration of exposure:
6
Justification:
Adjustment from subacute to chronic duration
AF for interspecies differences (allometric scaling):
4
Justification:
Extrapolation from rats to humans
AF for other interspecies differences:
2.5
Justification:
No substance-specific data are available; the additional factor of 2.5 is applied for other interspecies differences (toxicokinetic differences not related to metabolic rate - small part- and toxicodynamic differences - larger part).
AF for intraspecies differences:
5
Justification:
Default factor for workers is applied.
AF for the quality of the whole database:
1
Justification:
Good/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:
Dermal
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:
acute toxicity

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

The DNEL values for inhalation and dermal route, were calculated using as starting point a NOAEL of 1000 mg/kg bw day. This value was found in the study carried out according to the OECD guideline 422 on the Similar Substance 01. However, for repeated dose toxicity and reproductive toxicity, data coming from sub-chronic and chronic studies are available for other similar substances (Read Across Hypothesis and Justification attached in section 13). The NOAEL values found for these substances are always above 1000 mg/kg bw day.

The selection of the NOAEL value deriving from a sub-acute study was done following a conservative approach as higher assessment factors were applied in the calculation of DNELs.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.5 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):
150
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
375 mg/m³
Explanation for the modification of the dose descriptor starting point:

No long-term exposure data is available for the inhalation route therefore the NOAEL resulted from an animal study where the substance was orally administered for 29 and 44 -50 days to male and female rats, respectively, is used.

Route-to-route extrapolation is therefore 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 (60 kg) and dividing the default human breathing volume referring to general population (20 m3in 24 hours and basal caloric demand) this dose is then translated into an air concentration.

The absorption rate for human via inhalation is not known for the substance. It is assumed that absorption rate via inhalation route is similar to absorption rate via oral route.

NOAELoral= 1000 mg/kg b.w

Standard human body weight = 60 kg

Default human breathing volume for general population for 24 hours = 20 m3

A correction factor of 0.5 is used due to differences in bioavailability.

Therefore, NOAECinh= (1000/4)* (60/20)* 0.5 = 375 mg/m3

AF for dose response relationship:
1
Justification:
The starting point for the DNEL derivation is a NOAEL; default factor AF=1 is used.
AF for differences in duration of exposure:
6
Justification:
The duration of the animal study is 29-50 days. Extrapolation needed from subacute to chronic.
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling 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:
Good/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

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:
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:
1.67 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):
600
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No long-term exposure data is available for the dermal route therefore the NOAEL resulted from an animal study where the substance was orally administered for 29 days to male rats and 44 -50 days to female rats, is used.

No route-to-route extrapolation needed. It is assumed that dermal absorption will not be higher than oral absorption; default factor is 1.

AF for dose response relationship:
1
Justification:
NOAEL was used; default AF is 1.
AF for differences in duration of exposure:
6
Justification:
Extrapolation for sub-acute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
No adjustment for direct chemical reactivity with membrane
AF for other interspecies differences:
2.5
Justification:
No adjustment for direct chemical reactivity with membrane
AF for intraspecies differences:
10
Justification:
Default value for general population
AF for the quality of the whole database:
1
Justification:
Good/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:
Dermal
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:
acute toxicity

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.67 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):
600
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The NOAEL resulted from an animal study where the substance was orally administered for 29 days to male rats and 44 -50 days to female rats, is used.

AF for dose response relationship:
1
Justification:
The starting point for the DNEL derivation is a NOAEL; default factor AF=1 is used.
AF for differences in duration of exposure:
6
Justification:
Extrapolation for sub-acute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling from rat 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:
Good/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:
low hazard (no threshold derived)

Additional information - General Population

The DNEL values for inhalation, dermal and oral route, were calculated using as starting point a NOAEL of 1000 mg/kg bw day. This value was found in the study carried out according to the OECD guideline 422 on the Similar Substance 01. However, for repeated dose toxicity and reproductive toxicity, data coming from sub-chronic and chronic studies are available for other similar substances (Read Across Hypothesis and Justification attached in section 13). The NOAEL values found for these substances are always above 1000 mg/kg bw day.

The selection of the NOAEL value deriving from a sub-acute study was done following a conservative approach as higher assessment factors were applied in the calculation of DNELs.