Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/m³
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/m³
DNEL related information

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
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:
0.4 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):
75
Modified dose descriptor starting point:
NOAEL
Value:
30 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
no AF needed from oral to dermal routes
AF for dose response relationship:
1
Justification:
clear dose-responce relation established
AF for differences in duration of exposure:
6
Justification:
defalut; from subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
the NOAEL determining factor was the irritation effect in the gastro-intestinal tract
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
5
Justification:
default
AF for the quality of the whole database:
1
Justification:
studies of Klimish 1; consistent results in all available studies
AF for remaining uncertainties:
1
Justification:
robust and reliable read-across, comparable potencies for the registration substance and the read-across supporting substance demonstrated.
Acute/short term exposure
Hazard assessment conclusion:
no DNEL required: short term exposure controlled by conditions for long-term
DNEL related information

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:
no DNEL required: short term exposure controlled by conditions for long-term

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 (2013). 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, 2013).

Overall, the applicability domain of the DNEL of 1 mg/m3for corrosive substances is defined as follows (Messinger, 2013):

- 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.

With this DNEL for local effects, any potential systemic effects are covered as well.

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

It is reasonable to derive the local respiratory effect as the most sensitive endpoint upon inhalation, which can be derived from the following observations:

- the irritation effect in the gastro-intestinal tract was the NOAEL determing factor in oral repeated dose toxicity studies (OECD 421 on the registration substance and OECD 422 studies on the read-across supporting substance); no effect attributable to systemic exposure could be found.

- the substance is corrosive to skin and eye,

- the substance is highly cytotoxic (in the preliminary cytotoxicity studies in the provided in-vitro genotoxicity studies).

Therefore, the use of DNEL(long-term, local ) is considered to be sufficiently protective for the potential systemic effect.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.5 mg/m³
DNEL related information
DNEL derivation method:
other: The AF of 2 is additionally applied to the corresponding DNEL for workers.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.5 mg/m³
DNEL related information
DNEL derivation method:
other: The AF of 2 is additionally applied to the corresponding DNEL for workers.

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.5 mg/m³
DNEL related information
DNEL derivation method:
other: An AF of 2 is additionally applied to the corresponding DNEL for workers
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.5 mg/m³
DNEL related information
DNEL derivation method:
other: An AF of 2 is additionally applied to the corresponding DNEL for workers.

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.2 mg/kg bw/day
DNEL related information
DNEL derivation method:
other: An AF of 2 is additionally applied to the corresponding DNEL for workers.
Acute/short term exposure
Hazard assessment conclusion:
no DNEL required: short term exposure controlled by conditions for long-term
DNEL related information

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:
no DNEL required: short term exposure controlled by conditions for long-term

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.2 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):
150
Modified dose descriptor starting point:
NOAEL
Value:
30 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
no extrapolation needed
AF for dose response relationship:
1
Justification:
clear dose-response relations observed in all available studies
AF for differences in duration of exposure:
6
Justification:
default; from subacute to subchronic
AF for interspecies differences (allometric scaling):
1
Justification:
the NOAEL determining factor was the irritation effect in the gastro-intestinal tract
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
10
Justification:
default
AF for the quality of the whole database:
1
Justification:
studies of Klimish 1; consistent results in all available studies
AF for remaining uncertainties:
1
Justification:
robust and reliable read-across, comparable potencies for the registration substance and the read-across supporting substance demonstrated.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.2 mg/kg bw/day
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population