Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.18 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):
35
Dose descriptor starting point:
NOAEL
DNEL value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
44 mg/m³
Explanation for the modification of the dose descriptor starting point:

The Starting point for the DNEL derivation (long term systemic, inhalation) is taken as the NOAEL for systemic effects of 50 mg/kg bw from the 2 - generation reproductive toxicity study.

The critical effects in this study were increases in Kidney weight in the top dose (150 mg/kg bw) in the parent and F1 parent generations.

Starting NOAEL = 50 mg/kg bw/day. Converted to Dose descriptor starting point according to ECHA guidance (practical guide 14). 50/0.38 x 0.67 x 0.5 = 44 mg/m3 ; It is assumed that the oral absorption rate is 50% of that of the inhalation absorption. This is a conservative assessment since the available TK data demonstrate >90% absorption via the oral route.

AF for dose response relationship:
1
Justification:
Clear dose response with minimal toxicological findings up to the highest dose in the key study
AF for differences in duration of exposure:
3
Justification:
A multigeneration study is used as the starting point which is similar in duration of the animals to a 90 day study.
AF for interspecies differences (allometric scaling):
1
Justification:
not required due to route to route extrapolation method
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
5
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
ECHA Default
AF for remaining uncertainties:
1
Justification:
not required
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.45 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
6
Dose descriptor:
NOAEC
AF for dose response relationship:
1
Justification:
ECHA default
AF for differences in duration of exposure:
2
Justification:
The local effects are associated with concentration in the upper respiratory tract rather than the duration of exposure. Experience demonstrates that increasing the duration of exposure does not result in a non-irritating exposure level becoming irritating. Therefore a reduced factor of 2 has been allocated.
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA Default
AF for other interspecies differences:
1
Justification:
human will be less sensitive than rats in inhalation due to the local effect
AF for intraspecies differences:
3
Justification:
Deviation from ECHA default due to lower variability for local effects - this approach is consistent with that adopted by SCOEL when setting OELS based on local irritation effects.
AF for the quality of the whole database:
1
Justification:
ECHA Default
AF for remaining uncertainties:
1
Justification:
not required
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:
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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

Due to the potential for inhalation exposure (volatility is low, but uses involve spraying of the substance as part of a 2 component coating system), DNELs have been derived for local and systemic effects via inhalation (long term only).

The toxicity of this substance is limited to local effects only (Specifically irritation to the skin, eyes, respiratory system, and skin sensitising potential). In repeated dose toxicity studies there were no treatment related systemic effects (refer to repeated dose and reproductive toxicity sections). As such, protecting against local effects will protect against any systemic toxicity.

The local effects DNEL for inhalation (long term) is derived using the 90 -day inhalation study.

The systemic toxicity DNEL for inhalation (long term) is derived using the 2 -gen oral toxicity study in rats. The 90 -day inhalation study is not used as the starting point for the DNEL as the top dose was limited by local effects, and as such, although it was a NOEL for systemic toxicity, it is likely the actual NOEL for systemic toxicity is higher. Therefore the systemic toxicity NOAEL from the 2 -gen study is used with the appropriate assessment factors to account for dose duration.

DNELS for the dermal route of exposure have not been calculated since this substance is a skin sensitiser. Protection against sensitising potential will therefore protect against potential local irritation effects and systemic toxicity. Please refer to Sections 9 and 10 of the chemical safety report, and section 11 of the IUCLID for the personal protective equipment recommendations when handling this substance.

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:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Route of original study:
Dermal
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:
no hazard 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

There are no consumer uses for this substance