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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:
25.55 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
34.5
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
668 mg/m³
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.33 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
60
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
100 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEL

Local effects

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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

The substance is not acutely toxic following oral and dermal routes of exposure at any dose tested. Inhalation exposure is unlikely to occur because the substance only exists in liquid form and it will not be aerosolised in its normal use pattern. In addition, no toxicity was observed in an acute inhalation study at the highest exposure concentration technically feasible. On this basis, derivation of Acute systemic DNELs is not required as no acute toxicity has been identified by any route of exposure.

The substance is not irritating either to the skin and eye. However, the substance was shown to cause skin sensitisation in well conducted animal studies. No threshold can be established based on available data. On this basis, derivation of Acute DN(M)ELs for local effects is not possible. A qualitative assessment of the hazard indicates the need to manage potential skin contact including avoiding contact with substance or products that contain it at >/= 1.0 wt%.

The long-term dermal DNEL has been derived based on the fully compliant OECD 415 One Generation Reproductive Toxicity gavage study in which no systemic effects were noted. The NOAEL of 500 mg/kg bw/day for systemic effects has been used, considering 100% dermal absorption as a worst-case assumption. The long-term inhalation DNEL for systemic effects has been extrapolated from the same study with the same absorption assumption.

Setting a dermal DN(M)EL for long-term local effects was not considered appropriate because the substance was shown to cause skin sensitization but no eye or skin irritation under acute exposure conditions. Sufficient data are not available to extrapolate a DMEL. A qualitative assessment indicates that dermal exposure should be managed and avoided for the substance and products containing it at >/= 1.0wt%.

All assessment factors used for the derivation of the DNEL values were taken from the ECHA guidance document "Guidance on information requirements and chemical safety assessment; Chapter R.8: Characterisation of dose [concentration]-response for human health.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
11.8 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
75
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
267.2 mg/m³
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
25
Modified dose descriptor starting point:
NOAEC

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:
DNEL (Derived No Effect Level)
Value:
4.17 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
120
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
50 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL

Local effects

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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.7 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
300
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Value:
50 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

The same end points have been used to derive DNELs for the general population. The increased AF of 10 for intraspecies sensitivity is considered to be sufficiently protective.

All assessment factors use for the derivation of the DNEL values were taken from the ECHA guidance document "Guidance on information requirements and chemical safety assessment; Chapter R.8: Characterisation of dose [concentration]-response for human health.

Dermal Route:

Physicochemical properties have a decisive influence on the penetration of molecules through the skin. EC# 271-877-7 has Log Kow 5.8 and mean molecular weight from 774- 886. According to [Guidance Document on Dermal Absorption, European Commission; 2004], maximal absorption occurs when Log Kow is between 1 and 2 and absorption decreases as MW >500. Based on these criteria, chemical parameters are not favorable for EC 271-877-7 to be absorbed when in contact with skin.

This assumption can be confirmed by QSAR assay which calculates dermal penetration coefficient (Kp) or Pd (the permeability of the skin) by using empirical formulas.