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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.29 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):
75
Dose descriptor starting point:
NOAEL
DNEL value:
200 mg/kg bw/day
DNEL value:
246.8 mg/m³
Explanation for the modification of the dose descriptor starting point:

DNEL based on NOAEL (OECD 407, oral) in rats:

- NOAEC (inhalation) derived according to “DNEL calculator" included in IUCLID.

corrected NOAEC(inhalation) = NOAEL(oral, rat) x 1/sRVratxABS(oral-rat)/ABS(inh-human) x sRVhuman/wRV

= 200 mg/kg x 1/0.38 m3/kg/d x 50%/100% x 6.7 m3/10 m3

= 176.3 mg/m3

with sRV: standard respiratory volume; ABS: Absorption; wRV: worker respiratory volume

A correction for the differences between human and experimental exposure conditions (EXPCOND) is made in the DNEL calculator:

176.3 mg/m³ x 7/5 = 246.8 mg/m³

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
6
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
5
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
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
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:
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
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:
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/acute 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/m3 that 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. Overall, the applicability domain of the DNEL of 1 mg/m3 for corrosive substances is defined as follows (Messinger, 2014):

- The substance is not a CMR substance, not a heavy metal derivative, not 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/m3 can 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

The substance is classified for human health as corrosive to the skin (and assumed corrosive to the eye). The hazard statement H314: Causes severe skin burns and eye damage, is applicable. No DNEL for systemic effects is derived since the corrosive properties of the substance determine the hazard and risk profile. Otherwise, dermal systemic exposure would have to be calculated, which would then assume (even if gloves are worn) some dermal exposure to the substance. This cannot reflect the real situation since the skin would suffer from the corrosive effects. Rather than calculating some dermal exposure potentially leading to systemic effects and discounting these results afterwards on the basis of the corrosive effects, it is more appropriate to base the dermal assessment entirely on the qualitative risk characterisation for a corrosive substance.

Based on the classification and the hazard statement a moderate hazard band for the qualitative assessment is assumed.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.58 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):
150
Dose descriptor starting point:
NOAEL
DNEL value:
200 mg/kg bw/day
DNEL value:
86.96 mg/m³
Explanation for the modification of the dose descriptor starting point:

DNEL based on NOAEL (OECD 422, oral) in rats:

- NOAEC (inhalation) derived according to “Guidance on information requirements and chemical safety assessment”, Chapter R.8.4.2, Figure R. 8-3 (p. 21).

corrected NOAEC (inhalation) = NOAEL (oral, rat) x 1/sRVrat x ABS(oral-rat)/ABS(inh-human)

= 200 mg/kg x 1/1.15 m3/kg/d x 50%/100%

= 86.96 mg/m3

with sRV: standard respiratory volume; ABS: Absorption

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
6
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
10
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
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
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:
0.333 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):
600
Dose descriptor starting point:
NOAEL
DNEL value:
200 mg/kg bw/day
DNEL value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Default (DNEL calculator)

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
6
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
10
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
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:
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:
0.333 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):
600
Dose descriptor starting point:
NOAEL
DNEL value:
200 mg/kg bw/day
DNEL value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Default (DNEL calculator)

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
6
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
10
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
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

VCI DNELs for inhalation local long-term and acute effects were applied as described ibove for workers.

The substance is classified for human health as corrosive to the skin (and assumed corrosive to the eye). The hazard statement H314: Causes severe skin burns and eye damage, is applicable. No DNEL for systemic effects is derived since the corrosive properties of the substance determine the hazard and risk profile. Otherwise, dermal systemic exposure would have to be calculated, which would then assume (even if gloves are worn) some dermal exposure to the substance. This cannot reflect the real situation since the skin would suffer from the corrosive effects. Rather than calculating some dermal exposure potentially leading to systemic effects and discounting these results afterwards on the basis of the corrosive effects, it is more appropriate to base the dermal assessment entirely on the qualitative risk characterisation for a corrosive substance.

Based on the classification and the hazard statement a moderate hazard band for the qualitative assessment is assumed.