Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
13.2 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):
10
Dose descriptor starting point:
NOAEL
Modified dose descriptor starting point:
NOAEC
Value:
132.2 mg/m³
Explanation for the modification of the dose descriptor starting point:
The original study is reliable without restrictions. The route to route extrapolation was performed by applying the equation as cited in Guidance on information requirements and chemical safety assessment, Chapter R.8 (by ECHA) with all recommended assessment factors.
AF for dose response relationship:
1
Justification:
NOAEL is the starting point for DNEL derivation. According to Guidance on information Chapter R.8, p. 30, the assessment factor is 1.
AF for differences in duration of exposure:
2
Justification:
according to Guidance on information Chapter R.8, Table 8-5, p. 29
AF for interspecies differences (allometric scaling):
1
Justification:
interspecies difference is included in the calculation by correcting the respiratory volumes of rat and man (for details refer to "justification and comments")
AF for other interspecies differences:
1
Justification:
interspecies difference is included in the calculation by correcting the respiratory volumes of rat and man (for details refer to "justification and comments")
AF for intraspecies differences:
5
Justification:
according to Guidance on information Chapter R.8, Table 8-6, p. 32
AF for the quality of the whole database:
1
Justification:
Original study is reliable without restriction
AF for remaining uncertainties:
1
Justification:
no further uncertainties assumed
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
948.6 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
5
Modified dose descriptor starting point:
NOAEC
Value:
4 742.9 mg/m³
Explanation for the modification of the dose descriptor starting point:
The original study is reliable. The route to route extrapolation was performed by applying the equation as cited in Guidance on information requirements and chemical safety assessment, Chapter R.8 (by ECHA) with all recommended assessment factors.
AF for dose response relationship:
1
Justification:
ived limit value is the acute DNEL and the starting point for derivation is the acute LD50 an assessment factor of 1 considered to be justified.
AF for interspecies differences (allometric scaling):
1
Justification:
Interspecies difference is included in the calculation by correcting the respiratory volumes of rat and man (for details refer to "justification and comments")
AF for other interspecies differences:
1
Justification:
Interspecies difference is included in the calculation by correcting the respiratory volumes of rat and man (for details refer to "justification and comments")
AF for intraspecies differences:
5
Justification:
according to Guidance on information Chapter R.8, Table 8-6, p. 32
AF for the quality of the whole database:
1
Justification:
Original study is reliable
AF for remaining uncertainties:
1
Justification:
no further uncertainties assumed

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/m³
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information
DNEL derivation method:
other: VCI inhalation DNEL for corrosive substances
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/m³
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information
DNEL derivation method:
other: VCI inhalation DNEL for corrosive substances

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.8 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):
40
Dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The original study is reliable without restrictions. The route to route extrapolation was performed by applying the equation as cited in Guidance on information requirements and chemical safety assessment, Chapter R.8 (by ECHA) with all recommended assessment factors.
AF for dose response relationship:
1
Justification:
NOAEL is the starting point for DNEL derivation. According to Guidance on information Chapter R.8, p. 30, the assessment factor is 1.
AF for differences in duration of exposure:
2
Justification:
according to Guidance on information Chapter R.8, Table 8-5, p. 29
AF for interspecies differences (allometric scaling):
4
Justification:
according to Guidance on information Chapter R.8, Table 8-3, p. 24
AF for other interspecies differences:
1
Justification:
no additional AF for interspecies differences assumed
AF for intraspecies differences:
5
Justification:
according to Guidance on information Chapter R.8, Table 8-6, p. 32
AF for the quality of the whole database:
1
Justification:
Original study is reliable without restriction
AF for remaining uncertainties:
1
Justification:
no further uncertainties assumed
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
134.5 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
20
Modified dose descriptor starting point:
NOAEL
Value:
2 690 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The original study is reliable. The route to route extrapolation was performed by applying the equation as cited in Guidance on information requirements and chemical safety assessment, Chapter R.8 (by ECHA) with all recommended assessment factors.
AF for dose response relationship:
1
Justification:
Since the derived limit value is the acute DNEL and the starting point for derivation is the acute LD50 an assessment factor of 1 considered to be justified.
AF for interspecies differences (allometric scaling):
4
Justification:
according to Guidance on information Chapter R.8, Table 8-3, p. 24
AF for other interspecies differences:
1
Justification:
no additional AF for interspecies differences assumed
AF for intraspecies differences:
5
Justification:
according to Guidance on information Chapter R.8, Table 8-6, p. 32
AF for the quality of the whole database:
1
Justification:
Original study is reliable
AF for remaining uncertainties:
1
Justification:
no further uncertainties assumed

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

Worker DNEL: Long-term/short term for inhalation route, local effects

The German VCI ("Verband der chemischen Industrie") established an inhalation DNEL for local effects for corrosive substances of 1 mg/m3that should be applied for long- and short-term exposure equally. The derivation of this value is fully described in Messinger (2014). Briefly, the DNEL is a generic cut-off value based on an extensive analysis of the German occupational exposure limit (OEL) values as published in TRGS 900 (“Technnische Regeln für Gefahrstoffe”) for substances that are legally classified as corrosive. Substances identified as corrosive in self-classifications only were not considered, since they lack a peer review of the classification assigned. After exclusion of some (groups of) substances, such as CMR substances, the evaluation retrieved 40 corrosive substances with OEL values effective in Germany. In addition to the dermal effects, corrosive substances often display pronounced acute toxicity when administered by other pathways, especially via inhalation. When all very toxic (R26 or R27 or R28) and all sensitising (R42 or R43) substances were removed from the set of 40 corrosive substances, only 2/24 (8%) substances had an OEL below 1 mg/m3. The two substances are 1) sulfuric acid, a very strong acid vigorously reacting with water and b) barium hydroxide, for which the low OEL was derived on the basis of systemic effects (Messinger, 2014).

Overall, the applicability domain of the DNEL of 1 mg/m3for corrosive substances is defined as follows (Messinger, 2014):

- The substance is not a CMR substance, a heavy metal derivative, a sensitiser and does not hydrolyse to strong acids/bases

- The substance is not very toxic by ingestion, dermal contact or inhalation.

The submission substance fulfils these criteria and the DNEL of 1 mg/m3can be applied.

Reference 

Messinger, H. (2014): An approach for the delineation of a generic cut-off value for local respiratory tract irritation by irritating or corrosive substances as a pragmatic tool to fulfill REACH requirements, Regulatory Toxicology and Pharmacology, 3, 317-324

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.3 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):
20
Dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
65.2 mg/m³
Explanation for the modification of the dose descriptor starting point:
The original study is reliable without restrictions. The route to route extrapolation was performed by applying the equation as cited in Guidance on information requirements and chemical safety assessment, Chapter R.8 (by ECHA) with all recommended assessment factors.
AF for dose response relationship:
1
Justification:
NOAEL is the starting point for DNEL derivation. According to Guidance on information Chapter R.8, p. 30, the assessment factor is 1.
AF for differences in duration of exposure:
2
Justification:
according to Guidance on information Chapter R.8, Table 8-5, p. 29
AF for interspecies differences (allometric scaling):
1
Justification:
interspecies difference is included in the calculation by correcting the respiratory volumes of rat and man (for details refer to "justification and comments")
AF for other interspecies differences:
1
Justification:
interspecies difference is included in the calculation by correcting the respiratory volumes of rat and man (for details refer to "justification and comments")
AF for intraspecies differences:
10
Justification:
according to Guidance on information Chapter R.8, Table 8-6, p. 32
AF for the quality of the whole database:
1
Justification:
Original study is reliable without restriction
AF for remaining uncertainties:
1
Justification:
no further uncertainties assumed
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
233.9 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC
Value:
2 339.1 mg/m³
Explanation for the modification of the dose descriptor starting point:
The original study is reliable. The route to route extrapolation was performed by applying the equation as cited in Guidance on information requirements and chemical safety assessment, Chapter R.8 (by ECHA) with all recommended assessment factors.
AF for dose response relationship:
1
Justification:
Since the derived limit value is the acute DNEL and the starting point for derivation is the acute LD50 an assessment factor of 1 considered to be justified.
AF for interspecies differences (allometric scaling):
1
Justification:
Interspecies difference is included in the calculation by correcting the respiratory volumes of rat and man (for details refer to "justification and comments")
AF for other interspecies differences:
1
Justification:
Interspecies difference is included in the calculation by correcting the respiratory volumes of rat and man (for details refer to "justification and comments")
AF for intraspecies differences:
10
Justification:
according to Guidance on information Chapter R.8, Table 8-6, p. 32
AF for the quality of the whole database:
1
Justification:
Original study is reliable
AF for remaining uncertainties:
1
Justification:
no further uncertainties assumed

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/m³
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information
DNEL derivation method:
other: VCI inhalation DNEL for corrosive substances.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/m³
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information
DNEL derivation method:
other: VCI inhalation DNEL for corrosive substances.

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.9 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):
80
Dose descriptor starting point:
NOAEL
Value:
150 mg/m³
Modified dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The original study is reliable without restrictions. The route to route extrapolation was performed by applying the equation as cited in Guidance on information requirements and chemical safety assessment, Chapter R.8 (by ECHA) with all recommended assessment factors
AF for dose response relationship:
1
Justification:
NOAEL is the starting point for DNEL derivation. According to Guidance on information Chapter R.8, p. 30, the assessment factor is 1.
AF for differences in duration of exposure:
2
Justification:
according to Guidance on information Chapter R.8, Table 8-5, p. 29
AF for interspecies differences (allometric scaling):
4
Justification:
according to Guidance on information Chapter R.8, Table 8-3, p. 24
AF for other interspecies differences:
1
Justification:
no additional AF for interspecies differences assumed
AF for intraspecies differences:
10
Justification:
according to Guidance on information Chapter R.8, Table 8-6, p. 32
AF for the quality of the whole database:
1
Justification:
Original study is reliable without restriction
AF for remaining uncertainties:
1
Justification:
no further uncertainties assumed
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
67.3 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
Value:
2 690 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The original study is reliable. The route to route extrapolation was performed by applying the equation as cited in Guidance on information requirements and chemical safety assessment, Chapter R.8 (by ECHA) with all recommended assessment factors.
AF for dose response relationship:
1
Justification:
Since the derived limit value is the acute DNEL and the starting point for derivation is the acute LD50 an assessment factor of 1 considered to be justified.
AF for interspecies differences (allometric scaling):
4
Justification:
according to Guidance on information Chapter R.8, Table 8-3, p. 24
AF for other interspecies differences:
1
Justification:
no additional AF for interspecies differences assumed
AF for intraspecies differences:
10
Justification:
according to Guidance on information Chapter R.8, Table 8-6, p. 32
AF for the quality of the whole database:
1
Justification:
Original study is reliable
AF for remaining uncertainties:
1
Justification:
no further uncertainties assumed

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.9 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):
80
Modified dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
n.a.; most sensitive endpoint study is repeated dose oral toxicity study
AF for dose response relationship:
1
Justification:
NOAEL is the starting point for DNEL derivation. According to Guidance on information Chapter R.8, p. 30, the assessment factor is 1.
AF for differences in duration of exposure:
2
Justification:
according to Guidance on information Chapter R.8, Table 8-5, p. 29
AF for interspecies differences (allometric scaling):
4
Justification:
according to Guidance on information Chapter R.8, Table 8-3, p. 24
AF for other interspecies differences:
1
Justification:
no additional AF for interspecies differences assumed
AF for intraspecies differences:
10
Justification:
according to Guidance on information Chapter R.8, Table 8-6, p. 32
AF for the quality of the whole database:
1
Justification:
Original study is reliable without restriction
AF for remaining uncertainties:
1
Justification:
no further uncertainties assumed
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
67.3 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
Value:
2 690 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
n.a.; most sensitive endpoint study is acute oral toxicity study
AF for dose response relationship:
1
Justification:
Since the derived limit value is the acute DNEL and the starting point for derivation is the acute LD50 an assessment factor of 1 considered to be justified
AF for interspecies differences (allometric scaling):
4
Justification:
according to Guidance on information Chapter R.8, Table 8-3, p. 24
AF for other interspecies differences:
1
Justification:
no additional AF for interspecies differences assumed
AF for intraspecies differences:
10
Justification:
according to Guidance on information Chapter R.8, Table 8-6, p. 32
AF for the quality of the whole database:
1
Justification:
Original study is reliable
AF for remaining uncertainties:
1
Justification:
no further uncertainties assumed

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

please refer to "justification and comments" of each hazard point