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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:
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
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
Route of original study:
Dermal
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Route of original study:
Dermal
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/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/m3 that 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/m3 for 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/m3 can be applied.

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

Reference 

Messinger, H.: An approach for the delineation of a generic cut-off value for local respiratory tract irritation by irritating or corrosive substances, 2013 (manuscript submitted for publication).

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:
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):
100
Modified dose descriptor starting point:
NOAEL
DNEL value:
50 mg/kg bw/day
AF for dose response relationship:
1
Justification:
no deficencies
AF for differences in duration of exposure:
1
Justification:
chronic study
AF for interspecies differences (allometric scaling):
4
Justification:
study performed with rats
AF for other interspecies differences:
2.5
Justification:
study performed with rats
AF for intraspecies differences:
10
Justification:
standard factor
AF for the quality of the whole database:
1
Justification:
no deficencies
AF for remaining uncertainties:
1
Justification:
no uncertainties
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

General population DNEL: Long-term for oral route, systemic effects

The DNEL long-term, oral exposure, systemic effects is derived from a toxicity study with oral exposure. The most sensitive NOAEL for this category was the NOAEL of 50 mg/kg bw/day identified in a chronic toxicity study with rats.

DNEL derivation:

Basis NOAEL: 50 mg/kg bw/day from a 2 -year oral toxicity study in rats

No specific values on oral absorption available, therefore default assumption for oral absorption: 100 %

Assessment factors:

·        Interspecies differences: 4 (allometric scaling), 2.5 (remaining differences)

·        Intraspecies differences: 10

·        Differences in duration of exposure: 1 (chronic study available)

·        Issues related to dose-response: 1 (none)

·        Quality of whole database: 1 (no deficiencies)

--> Overall assessment factor: 100

DNEL = 50 mg/kg bw/day / 100

DNEL = 0.5 mg/kg bw/day

An existing European evaluation is available. The European Food Safety Authority (EFSA), using the same experimental study in rats as the basis, derived a TDI for C12-20 -DMA (described by EFSA as "Alkyl, linear with even number of carbon atoms (C12 -C20) dimethylamines") that is identical to the DNEL derived here (0.5 mg/kg bw/d).

Reference

EFSA, European Food Safety Authority (2007): Scientific Opinion of the Panel on food additives, flavourings, processing aids and materials in contact with food (AFC) on a request related to a 16th list of substances for food contact materials, The EFSA Journal, 555-563, 1-31