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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
5.3 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:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
264.47 mg/m³
Explanation for the modification of the dose descriptor starting point:

The NOAEL of 300 mg/kg bw/day was used for the DNEL assessments based on the results from a 90 day repeated dose study and a one-generation reproductive toxicity study (OECD 415). The OECD 415 study concluded that the NOAEL was 200 mg/kg based on adverse effects observed at 500 mg/kg (and so 200 mg/kg was selected as it is the next highest dose level). The substance was not tested at 300 mg/kg in the OECD 415 study, and so it cannot refute the findings of the 90 day study that concluded a NOAEL of 300 mg/kg bw/day. Therefore the overall NOAEL is considered to be 300 mg/kg bw/day.

A modification of the dose descriptor starting point (oral to inhalation) was conducted. It is assumed as a worst case assumption that the oral absorption rate is 50% of that of the inhalation absorption.

The corrected dose descriptor (NOAEC) for inhalation was calculated in accordance with the ECHA Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health.

The conversion of an oral rat NOAEL into a corrected inhalatory NOAEC to assess human inhalatory exposure was performed using the modification of starting point equation as given in Figure R. 8-3 (see below) for workers (in the case of 8 hour exposure/day).

Default parameters for rats and humans (for 8 hour exposure) were used for the modification of starting point under the allometric scaling principle as given in Table R. 8-2 of the above ECHA guidance.

Conversion of an oral rate N(L)OAEL into a correct inhalatory N(L)OAEC to assess human inhalatory exposure:

For workers (in case of 8h exposure/day):

Corrected inhalatory N(L)OAEC = oral N(L)OAEL x (1 / sRVrat) x (ABSoral-rat / ABSinh-human) x (sRVhuman / wRV)

Corrected inhalatory N(L)OAEC= 300 mg/kg bw/day x (1 / 0.38 m3/kg/d) x (0.5) x (6.7 m3(8h) / 10 m3(8h)) = 264.47 mg/m3

Where:

ABS: Absorption

sRV: standard Respiratory Volume

wRV: worker Respiratory Volume (light activity)

Default parametrs:

sRVrat (8 h): 0.38m3/kg bw

sRVhuman (8 h): 6.7 m3/ person

wRV (8 h): 10 m3/ person

AF for dose response relationship:
1
Justification:
When the starting point for the DNEL calculation is a NOAEL the default assessment factor is 1.
AF for differences in duration of exposure:
2
Justification:
Default for subchronic to chronic studies (OECD 408 study)
AF for interspecies differences (allometric scaling):
1
Justification:
AF for allometric scaling not required as the differences in allometry (respiration rate and rate to human body sizes) were considered in the conversion from oral to inhalation starting point.
AF for other interspecies differences:
2.5
Justification:
Default AF for remaining interspecies differences.
AF for intraspecies differences:
5
Justification:
Default AF for worker population
AF for the quality of the whole database:
1
Justification:
Quality of data considered to be reliable.
AF for remaining uncertainties:
2
Justification:
An additional AF of 2 has been applied as the OECD 408 90-day repeat dose toxicity study has been read-across from a structurally similar analogue substance where the only difference between target and source molecules is the enantiomeric ratio. In the chiral environment of living organisms the enantiomers may possess different toxicities. Therefore, an additional AF has been considered applicable based on any minor potential differences between the enantiomers.
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:
0.94 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:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
187.5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

A skin absorption model (Shen et al., 2014) was used to predict a skin absorption of ≤ 80 % for the substance.

Absorption via the inhalation route is assumed to be 100% as a worst case assumption, whereas absorption via the oral route is assumed to be 50%. Therefore, an additional factor of 0.625 (50/80) is used for correction, assuming 50% absorption via the oral route of the original study.

Modified dose dsecriptor starting point = 300 x (50/80) = 187.5 mg/kg bw/day

AF for dose response relationship:
1
Justification:
When the starting point for the DNEL calculation is a NOAEL the default assessment factor is 1.
AF for differences in duration of exposure:
2
Justification:
Default for subchronic to chronic studies (OECD 408 study).
AF for interspecies differences (allometric scaling):
4
Justification:
Default AF for allometric scaling based on rats
AF for other interspecies differences:
2.5
Justification:
Default AF for remaining interspecies differences.
AF for intraspecies differences:
5
Justification:
Default AF for worker population
AF for the quality of the whole database:
1
Justification:
Quality of data considered to be reliable
AF for remaining uncertainties:
2
Justification:
An additional AF of 2 has been applied as the OECD 408 90-day repeat dose toxicity study has been read-across from a structurally similar analogue substance where the only difference between target and source molecules is the enantiomeric ratio. In the chiral environment of living organisms the enantiomers may possess different toxicities. Therefore, an additional AF has been considered applicable based on any minor potential differences between the enantiomers.
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

DNEL for long-term systemic effects have been derived for both inhalation and dermal routes, based on the results of an OECD 408 study. The NOAEL in this study was 300 mg/kg bw/day but DNELs have been derived as a worst case assessment.

The substance is not classified for human health or the environment, so exposure scenario's with risk characterisation are not required. These DNELs have therefore been provided for reference only and to further show the low inherent toxicity of the substance.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.3 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:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
130.43 mg/m³
Explanation for the modification of the dose descriptor starting point:

The NOAEL of 300 mg/kg bw/day was used for the DNEL assessments based on the results from a 90 day repeated dose study and a one-generation reproductive toxicity study (OECD 415). The OECD 415 study concluded that the NOAEL was 200 mg/kg based on adverse effects observed at 500 mg/kg (and so 200 mg/kg was selected as it is the next highest dose level). The substance was not tested at 300 mg/kg in the OECD 415 study, and so it cannot refute the findings of the 90 day study that concluded a NOAEL of 300 mg/kg bw/day. Therefore the overall NOAEL is considered to be 300 mg/kg bw/day.

A modification of the dose descriptor starting point (oral to inhalation) was conducted. It is assumed as a worst case assumption that the oral absorption rate is 50% of that of the inhalation absorption.

The corrected dose descriptor (NOAEC) for inhalation was calculated in accordance with the ECHA Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health.

The conversion of an oral rat NOAEL into a corrected inhalatory NOAEC to assess human inhalatory exposure was performed using the modification of starting point equation as given in Figure R. 8-3 (see below) for general population (in the case of 24 hour exposure/day).

Default parameters for rats and humans (for 24 hour exposure) were used for the modification of starting point under the allometric scaling principle as given in Table R. 8-2 of the above ECHA guidance.

Conversion of an oral rate N(L)OAEL into a correct inhalatory N(L)OAEC to assess human inhalatory exposure:

For general population (in case of 24h exposure/day):

Corrected inhalatory N(L)OAEC = oral N(L)OAEL x (1 / sRVrat) x (ABSoral-rat / ABSinh-human)

Corrected inhalatory N(L)OAEC= 300 mg/kg bw/day x (1 / 1.15 m3/kg/d) x (0.5) = 130.43 mg/m3

Where:

ABS: Absorption

sRV: standard Respiratory Volume

wRV: worker Respiratory Volume (light activity)

Default parametrs:

sRVrat (24 h): 1.15m3/kg bw

AF for dose response relationship:
1
Justification:
When the starting point for the DNEL calculation is a NOAEL the default assessment factor is 1.
AF for differences in duration of exposure:
2
Justification:
Default for subchronic to chronic studies (OECD 408 study)
AF for interspecies differences (allometric scaling):
1
Justification:
AF for allometric scaling not required as the differences in allometry (respiration rate and rate to human body sizes) were considered in the conversion from oral to inhalation starting point.
AF for other interspecies differences:
2.5
Justification:
Default AF for remaining interspecies differences.
AF for intraspecies differences:
10
Justification:
Default AF for general population
AF for the quality of the whole database:
1
Justification:
Quality of data considered to be reliable.
AF for remaining uncertainties:
2
Justification:
An additional AF of 2 has been applied as the OECD 408 90-day repeat dose toxicity study has been read-across from a structurally similar analogue substance where the only difference between target and source molecules is the enantiomeric ratio. In the chiral environment of living organisms the enantiomers may possess different toxicities. Therefore, an additional AF has been considered applicable based on any minor potential differences between the enantiomers.
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:
0.47 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:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
187.5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

A skin absorption model (Shen et al., 2014) was used to predict a skin absorption of ≤ 80 % for the substance.

Absorption via the inhalation route is assumed to be 100% as a worst case assumption, whereas absorption via the oral route is assumed to be 50%. Therefore, an additional factor of 0.625 (50/80) is used for correction, assuming 50% absorption via the oral route of the original study.

Modified dose dsecriptor starting point = 300 x (50/80) = 187.5 mg/kg bw/day

AF for dose response relationship:
1
Justification:
When the starting point for the DNEL calculation is a NOAEL the default assessment factor is 1.
AF for differences in duration of exposure:
2
Justification:
Default for subchronic to chronic studies (OECD 408 study).
AF for interspecies differences (allometric scaling):
4
Justification:
Default AF for allometric scaling based on rats
AF for other interspecies differences:
2.5
Justification:
Default AF for remaining interspecies differences
AF for intraspecies differences:
10
Justification:
Default AF for general population.
AF for the quality of the whole database:
1
Justification:
Quality of data considered to be reliable
AF for remaining uncertainties:
2
Justification:
An additional AF of 2 has been applied as the OECD 408 90-day repeat dose toxicity study has been read-across from a structurally similar analogue substance where the only difference between target and source molecules is the enantiomeric ratio. In the chiral environment of living organisms the enantiomers may possess different toxicities. Therefore, an additional AF has been considered applicable based on any minor potential differences between the enantiomers.
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:
0.75 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:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Route of exposure is the same as route of original study.

AF for dose response relationship:
1
Justification:
When the starting point for the DNEL calculation is a NOAEL the default assessment factor is 1.
AF for differences in duration of exposure:
2
Justification:
Default for subchronic to chronic studies (OECD 408 study).
AF for interspecies differences (allometric scaling):
4
Justification:
Default AF for allometric scaling based on rats
AF for other interspecies differences:
2.5
Justification:
Default AF for remaining interspecies differences
AF for intraspecies differences:
10
Justification:
Default AF for general population.
AF for the quality of the whole database:
1
Justification:
Quality of data considered to be reliable
AF for remaining uncertainties:
2
Justification:
An additional AF of 2 has been applied as the OECD 408 90-day repeat dose toxicity study has been read-across from a structurally similar analogue substance where the only difference between target and source molecules is the enantiomeric ratio. In the chiral environment of living organisms the enantiomers may possess different toxicities. Therefore, an additional AF has been considered applicable based on any minor potential differences between the enantiomers.
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

DNEL for long-term systemic effects have been derived for both inhalation and dermal routes, based on the results of an OECD 408 study. The NOAEL in this study was 300 mg/kg bw/day but DNELs have been derived as a worst case assessment.

The substance is not classified for human health or the environment, so exposure scenarios with risk characterisation are not required. These DNELs have therefore been provided for reference only and to further show the low inherent toxicity of the substance.