Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.4 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):
37.5
Modified dose descriptor starting point:
NOAEC
Value:
52.9 mg/m³
Explanation for the modification of the dose descriptor starting point:
for route extrapolation conditional decline (bw loss, decreased body weight gain and food consumption) is taken as systemic toxicity.
AF for dose response relationship:
1
Justification:
starting point is mid-dose NOAEL in a subacute (gavage) study + DRF study.
AF for differences in duration of exposure:
3
Justification:
The extrapolation factor from short term toxicity to the long-term scenario for a substance causing primary local toxicity is reduced by factor 2. For local irritation the concentration is in most cases the relevant parameter, and prolongation of exposure is expected to influence the severity of effect and morphology of changes, but not the NOAEL/NOAEC.
AF for interspecies differences (allometric scaling):
1
Justification:
allometric scaling is not applicable for inhalation
AF for other interspecies differences:
2.5
Justification:
default (not justified for local tox.)
AF for intraspecies differences:
5
Justification:
worker population
AF for the quality of the whole database:
1
Justification:
GLP compliant study data
AF for remaining uncertainties:
1
Justification:
No AF(2) for oral to inhalation extrapolation is applied as there is no scientific rational that the substance absorption by the oral route is less efficient than pullmonary absorption. Equal absorption for oral ingestion and inhalation has been assessed from physico-chemical properties of the substance.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.2 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12.5
DNEL extrapolated from long term DNEL
Modified dose descriptor starting point:
NOAEC
Value:
52.9 mg/m³
Explanation for the modification of the dose descriptor starting point:
for route extrapolation conditional decline (decreased body weight gain and decreased food consumption) is taken as systemic toxicity.
AF for dose response relationship:
1
Justification:
starting point is mid-dose NOAEL in a subacute (gavage) study
AF for interspecies differences (allometric scaling):
1
Justification:
not applicable for inhalation
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
5
Justification:
worker population
AF for the quality of the whole database:
1
Justification:
GLP compliant study data
AF for remaining uncertainties:
1
Justification:
No AF(2) for oral to inhalation extrapolation is applied as there is no scientific rational that the substance absorption by the oral route is less efficient than pullmonary absorption. Equal absorption for oral ingestion and inhalation has been assessed from physico-chemical properties of the substance.

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
irritation (respiratory tract)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.25 mg/kg bw/day
Most sensitive endpoint:
skin irritation/corrosion
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
1 800
Modified dose descriptor starting point:
LOAEL
Value:
450 mg/kg bw/day
AF for dose response relationship:
3
Justification:
starting point is low-dose LOAEL (conditional decline: bw loss, death) in a subacute dermal study
AF for differences in duration of exposure:
6
Justification:
The extrapolation factor from short term toxicity to the long-term scenario for a substance causing primary local toxicity is reduced by factor 2. For local irritation the concentration is in most cases the relevant parameter, and prolongation of exposure is expected to influence the severity of effect and morphology of changes, but not the NOAEL/NOAEC.
AF for interspecies differences (allometric scaling):
4
Justification:
rat
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
5
Justification:
worker population
AF for the quality of the whole database:
2
Justification:
non GLP, pre-guideline test without NOAEL, but CPSC-reviewed data in rats and rabbits
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties; no AF for read-across is necessary (see read across justification)
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:
0.05 mg/cm²
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
5
Dose descriptor:
other: NOAEL
AF for dose response relationship:
1
Justification:
MTD taken from chronic painting study in mice
AF for differences in duration of exposure:
1
Justification:
chronic NOAEL
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling to adjust for physiological based species differences is widely accepted for systemic toxic substances, but this does not apply to direct local effects.
AF for other interspecies differences:
1
Justification:
There is no evidence for differences in the general mode of action or kinetics, so there is no rational for an additional factor of 2.5 for remaining differences. This factor has no scientific basis, as the mode of action is direct chemical reactivity.
AF for intraspecies differences:
5
Justification:
worker population
AF for the quality of the whole database:
1
Justification:
MTD is considered reliable even if from non GLP, pre-guideline test; CPSC-reviewed data in mice
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties; no AF for read-across fromTHPC is necessary (see read across justification)
Acute/short term exposure
Hazard assessment conclusion:
no DNEL required: short term exposure controlled by conditions for long-term
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

The substance is characterised by primary local toxicity (irritation or corrosion) depending on the concentration applied. No significant inhalation exposure is expected. Systemic toxicity was seen after repeated oral and dermal (read-across) exposure to high doses. In order to perform a quantitative risk assessment, a dermal long-term systemic DNEL was calculated based on the sub-acute LOAEL (THPC: conditional decline, death) in rats. The dermal long-term local DNEL was calculated based on the NOAEL (THPC) from a chronic mice study. The inhalation DNELs were extrapolated from an maternal NOAEL (conditional decline) with the substance. The latter were found to be close to the TLV-TWA (US-ACGIH) for THPC, a closely related, precursor 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:
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:
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