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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
17.62 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
Modified dose descriptor starting point:
NOAEC
Value:
881.05 mg/m³
Explanation for the modification of the dose descriptor starting point:
Route to route extrapolation required for oral to inhalation route as no inhalation study available.
AF for dose response relationship:
1
Justification:
When the starting point for the DNEL calculation is a NOAEL, a default assessment factor is 1 considered applicable.
AF for differences in duration of exposure:
2
Justification:
Default AF for subchronic to chronic studies considered applicable as test material administration for 108 days.
AF for interspecies differences (allometric scaling):
1
Justification:
AF for allometric scaling not required as the differences in allometry (respiration rate and rat 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:
Relevant studies conducted to GLP and considered to be of reliability 1.
AF for remaining uncertainties:
2
Justification:
An additional AF of 2 is applied as the repeat dose toxicity result has been read-across from a comparable supporting substance (structural analogue). Therefore an additional AF has been considered appropriate to address the additional uncertainty factor of using read-across data, such as minor potential differences between the absorption and toxicity of the substances.
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:
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):
200
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Route to route extrapolation required for oral to inhalation route as no inhalation study available.
AF for dose response relationship:
1
Justification:
When the starting point for the DNEL calculation is a NOAEL, a default assessment factor is 1 considered applicable.
AF for differences in duration of exposure:
2
Justification:
Default AF for subchronic to chronic studies considered applicable as test material administration for 108 days.
AF for interspecies differences (allometric scaling):
4
Justification:
Default AF for 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:
Relevant studies conducted to GLP and considered to be of reliability 1.
AF for remaining uncertainties:
2
Justification:
An additional AF of 2 is applied as the repeat dose toxicity result has been read-across from a comparable supporting substance (structural analogue). Therefore an additional AF has been considered appropriate to address the additional uncertainty factor of using read-across data, such as minor potential differences between the absorption and toxicity of the substances.
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

Inhalation:

Inhalation is not considered to be a significant route of exposure. However, a long-term DNEL for systemic effects have been derived, based on the results obtained from a one generation reproductive study in the rat with evaluation of subchronic toxicity (OECD 408 and 415) on a structurally similar, comparable substance.

Long-term systemic effects:

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. In practice this is unlikely to be the case based on the particle size distribution.

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= 1000 mg/kg bw/day x (1 / 0.38 m3/kg/d) x (0.5) x (6.7 m3(8h) / 10 m3(8h))= 881.05 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

The appropriate assessment factors were then applied to give an overall assessment factor of 50.

Long-term systemic DNEL (inhalation) = 17.62 mg/m3

This long-term inhalation systemic effect DNEL is used in the quantitative assessment of risk for systemic toxicity to workers via the inhalation route.

Local inhalation effects are not considered to be of concern due to inhalation not being a significant route of exposure.

Dermal:

A DNEL has been derived for long-term systemic effects by the dermal route, based on the results obtained from a one generation reproductive study in the rat with evaluation of subchronic toxicity (OECD 408 and 415) on a structurally similar, comparable substance.

Long-term systemic DNEL (dermal) = 5 mg/kg bw/day

This long-term dermal systemic effect DNEL is used in the quantitative assessment of risk for systemic toxicity to workers via the dermal route.

DNELs for local effects have not been derived but the substance is a skin sensitiser, so has been classed as a medium hazard for local effects. A qualitative assessment is considered sufficient for any possible local effects (sensitisation), taking into account use of PPE and industrial/professional use conditions.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

There is no anticipated exposure to the general public/consumers, as there are no consumer uses of the substance.

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:
no hazard identified
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:
2.5 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
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Not required as NOEAL from an oral study.
AF for dose response relationship:
1
Justification:
When the starting point for the DNEL calculation is a NOAEL, a default assessment factor is 1 considered applicable.
AF for differences in duration of exposure:
2
Justification:
Default AF for subchronic to chronic studies considered applicable as test material administration for 108 days.
AF for interspecies differences (allometric scaling):
4
Justification:
Default AF for 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 public
AF for the quality of the whole database:
1
Justification:
Relevant studies conducted to GLP and considered to be of reliability 1.
AF for remaining uncertainties:
2
Justification:
An additional AF of 2 is applied as the repeat dose toxicity result has been read-across from a comparable supporting substance (structural analogue). Therefore an additional AF has been considered appropriate to address the additional uncertainty factor of using read-across data, such as minor potential differences between the absorbsion and toxicity of the substances.
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

DNELs have not been derived for the general public (apart from via the oral route for systemic effects) as there is no anticipated exposure to the general public/consumers, as there are no consumer uses of the substance. The only uses are industrial and heavy professional use.

A DNEL for long term systemic effects via the oral route has been derived, in order to assess indirect exposure of humans via the environment.