Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7.1 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):
25
Dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
176 mg/m³
Explanation for the modification of the dose descriptor starting point:

In the 90-day repeated dose toxicity study (oral gavage), the effects observed were primarily damage to respiratory tract as a result of reflux of test item, and damage to intestinal mucosa. Both effects are local effects considered to be the result of the irritant nature of the test substance. An increased incidence of irregular oestrous cycle and/or acyclic oestrous cycles was observed at 300 and 1000 mg/kg bw/day. These changes could have occurred due to the low and/or reduced body weight of those individual females at the end of the treatment period and are considered to be adverse, however, as a conservative approach the low-dose, 100 mg/kg bw/day, was considered to be the no-observed-adverse-effect level (NOAEL)

and used as the starting point for calculation of the systemic DNEL (inhalation).

The following correction was made to the NOAEL (oral): Correction respiratory volume rat (8 hour) 1/0.38 m³/kg bw/day, Correction for respiratory volume (worker): 6.7 m³/10 m³. Therefore the corrected NOAEC for repeated-dose systemic effects via the inhalation route is: 100*(1/0.38) *(6.7/10) = 176 mg/m³.

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
2
Justification:
Default (subchronic to chronic)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (oral, rat to inhaled, human)
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
5
Justification:
Default (worker)
AF for the quality of the whole database:
1
Justification:
Default (guideline study)
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
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)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 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):
100
Dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

In the 90-day repeated dose toxicity study (oral gavage), the effects observed were primarily damage to respiratory tract as a result of reflux of test item, and damage to intestinal mucosa. Both effects are local effects considered to be the result of the irritant nature of the test substance. An increased incidence of irregular oestrous cycle and/or acyclic oestrous cycles was observed at 300 and 1000 mg/kg bw/day. These changes could have occurred due to the low and/or reduced body weight of those individual females at the end of the treatment period and are considered to be adverse, however, as a conservative approach the low-dose, 100 mg/kg bw/day, was considered to be the no-observed-adverse-effect level (NOAEL).

No modification of dose descriptor is required for oral to dermal extrapolation.

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
2
Justification:
Default (subchronic to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (oral, rat to dermal, human)
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
5
Justification:
Default (worker)
AF for the quality of the whole database:
1
Justification:
Default (guideline study)
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties
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:
medium hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.7 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:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
87 mg/m³
Explanation for the modification of the dose descriptor starting point:

In the 90-day repeated dose toxicity study (oral gavage), the effects observed were primarily damage to respiratory tract as a result of reflux of test item, and damage to intestinal mucosa. Both effects are local effects considered to be the result of the irritant nature of the test substance. An increased incidence of irregular oestrous cycle and/or acyclic oestrous cycles was observed at 300 and 1000 mg/kg bw/day. These changes could have occurred due to the low and/or reduced body weight of those individual females at the end of the treatment period and are considered to be adverse, however, as a conservative approach the low-dose, 100 mg/kg bw/day, was considered to be the no-observed-adverse-effect level (NOAEL) and used as the starting point for calculation of the systemic DNEL (inhalation).

The following correction was made to the NOAEL (oral): Correction respiratory volume rat (24 hour) 1/1.15 m³/kg bw. Therefore the corrected NOAEC for repeated-dose systemic effects via the inhalation route is: 100*(1/1.15) = 87.0 mg/m³

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
2
Justification:
Default (subchronic to chronic)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (rat, oral to human, inhaled)
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default (general population)
AF for the quality of the whole database:
1
Justification:
Default (guideline study)
AF for remaining uncertainties:
1
Justification:
Default (no remaining uncertainties)
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)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.5 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
Dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

In the 90-day repeated dose toxicity study (oral gavage), the effects observed were primarily damage to respiratory tract as a result of reflux of test item, and damage to intestinal mucosa. Both effects are local effects considered to be the result of the irritant nature of the test substance. An increased incidence of irregular oestrous cycle and/or acyclic oestrous cycles was observed at 300 and 1000 mg/kg bw/day. These changes could have occurred due to the low and/or reduced body weight of those individual females at the end of the treatment period and are considered to be adverse, however, as a conservative approach the low-dose, 100 mg/kg bw/day, was considered to be the no-observed-adverse-effect level (NOAEL). For infrequent exposure of consumers, no assessment factor for differences in duration of exposure is required. No modification of dose descriptor is required for oral to dermal extrapolation.

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
2
Justification:
Default (subchronic to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (rat, oral to human, dermal)
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default (general population
AF for the quality of the whole database:
1
Justification:
Default (guideline study)
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
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)

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:
medium hazard (no threshold derived)

Additional information - General Population