Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.64 mg/m³
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Modified dose descriptor starting point:
NOAEC
DNEL value:
66.08 mg/m³
Explanation for the modification of the dose descriptor starting point:
Route to route extrapolation required for oral to inhalation route as no long-term inhalation study available.
AF for dose response relationship:
1
Justification:
The starting point for the DNEL calculation is a NOAEL, therefore an assessment factor of 1 is applicable.
AF for differences in duration of exposure:
2
Justification:
AF for subchronic to chronic studies (OECD 422 is considered to resemble a chronic study based on study design).
AF for interspecies differences (allometric scaling):
1
Justification:
AF for allometric scaling not required as the differences in allometry were considered in the conversion of oral to inhalation starting point.
AF for other interspecies differences:
2.5
Justification:
Default AF for remaining differences.
AF for intraspecies differences:
5
Justification:
Default AF for workers
AF for the quality of the whole database:
1
Justification:
All relevant studies conducted to GLP and reliability 1.
AF for remaining uncertainties:
1
Justification:
None identified.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.75 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
DNEL value:
75 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Route to route extrapolation required for oral to dermal route as no long-term dermal study available.
AF for dose response relationship:
1
Justification:
The starting point for the DNEL calculation is a NOAEL, therefore an assessment factor of 1 is applicable.
AF for differences in duration of exposure:
2
Justification:
AF for subchronic to chronic studies (OECD 422 is considered to resemble a chronic study based on study design).
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 differences
AF for intraspecies differences:
5
Justification:
Default AF for workers
AF for the quality of the whole database:
1
Justification:
All relevant studies conducted to GLP and reliability 1
AF for remaining uncertainties:
1
Justification:
None identified.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

The substance is classified for human health as a skin sensitiser.

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 OECD 422 Oral (Gavage) Combined Repeat Dose Toxicity Study With Reproduction / Developmental Toxicity Screening Test in the Rat conducted on the 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 and substance being considered to be essentially non-inhalable.

The corrected dose descriptor (LOAEC) 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 LOAEL into a corrected inhalatory LOAEC to assess human inhalatory exposure was performed using the modification of starting point equation as given in Figure R. 8-3 in ECHA Guidance: Characterisation of dose [concentration] - response for human health (Chapter R.8) (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= 75 mg/kg bw/day x (1 / 0.38 m3/kg/d) x (0.5) x (6.7 m3(8h) / 10 m3(8h))= 66.08 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 25.

Long-term systemic DNEL (inhalation)= 2.64 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. The long-term DNEL shall also cover short-term exposure.

Dermal:

A DNEL has been derived for long-term systemic effects by the dermal route, based on the results obtained OECD 422 Oral (Gavage) Combined Repeat Dose Toxicity Study With Reproduction / Developmental Toxicity Screening Test in the Rat conducted on the substance.

Long-term systemic DNEL (dermal) = 0.75 mg/kg bw/day

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

Although the substance is a moderate skin sensitiser, DNELs for local effects have not been derived as the study did not give adequate data for an accurate DNEL to be determined. It is also considered that a qualitative assessment of risk for local effects to works is sufficient.

General Population - Hazard via inhalation 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
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:
0.38 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
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
DNEL value:
75 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Not required
AF for dose response relationship:
1
Justification:
The starting point for the DNEL calculation is a NOAEL, therefore an assessment factor of 1 is applicable.
AF for differences in duration of exposure:
2
Justification:
AF for subchronic to chronic studies (OECD 422 is considered to resemble a chroic study based on study design).
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 differences.
AF for intraspecies differences:
10
Justification:
Default AF for general population.
AF for the quality of the whole database:
1
Justification:
All relevant studies conducted to GLP and reliability 1.
AF for remaining uncertainties:
1
Justification:
None identified.
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 will be no exposure to the general public/consumers as the substance only has industrial applications.

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.