Registration Dossier

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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3 088 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor starting point:
NOAEC
Value:
115 210 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
77 191 mg/m³
Explanation for the modification of the dose descriptor starting point:

No route to route extrapolation.

The point of departure is a 90-day rat inhalation, rats were exposed 6 h/day, 5 days/week

The effects observed in the available studies of various durations (14, 28 or 90 days, developmental toxicity study) with the analogue substance considered of greater reactivity indicate no increased severity of the effects with time, but more concentration-driven effects (irritation and anaesthetic levels, or liver adaptative effects) that were associated with the highest concentrations.

Thus, no concentration-time correction is applied to the NOAEC in the DNEL derivation.

(NOAEC) 115210 mg/m³ * 6.7 m³ (8h) / 10 m³ (8 h worker light activity) = 77190.7 mg/m³

AF for dose response relationship:
1
Justification:
No adverse effect observed at this concentration
AF for differences in duration of exposure:
2
Justification:
Sub chronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Not applicable when setting an inhalation DNEL based on an inhalation animal study
AF for other interspecies differences:
2.5
Justification:
Default value: Remaining differences
AF for intraspecies differences:
5
Justification:
Worker
AF for the quality of the whole database:
1
Justification:
All studies carried out under GLP, K1
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties, the surrogate is very close to the target substance.
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

Workers - 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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Basing on the analogue approach between GALDEN LMW and H GALDEN, as described in the appropriate sections and attachments of the dossier, it can be concluded that GALDEN LMW is expected to have the same toxicological profile as H GALDEN. The starting point NOAEC = 115210 mg/m³ derived from a 13 week inhalation toxicity study on H GALDEN is even considered a worst case approach because of the greater reactivity of H GALDEN in respect to GALDEN LMW. This consideration allows being on the safe side in regard to the potential hazard of GALDEN LMW following repeated dose exposure by inhalation

The NOThe NOAEC of 115210 mg/m3 is therefore used as the starting point for the derivation of long-term systemic inhalation DNEL value for workers.

The effects observed in the available studies of various durations (14, 28 or 90 days, developmental toxicity study) with the analogue substance considered of greater reactivity indicate no increased severity of the effects with time, but more concentration-driven effects (irritation and anaesthetic levels, or liver adaptative effects) that were associated with the highest concentrations. Thus, no concentration-time correction is applied to the NOAEC in the DNEL derivation.

GALDEN LMW is not classified for acute toxicity; acute systemic inhalation and acute dermal toxicity. Also, the skin sensitization test is negative. DNEL values are therefore not calculated, in the absence of any hazard.

The substance is not a skin or eye irritant; data available from acute inhalation toxicity study indicate that no respiratory irritation occurs. Local inhalation DNEL values are therefore not calculated.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2 304 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Dose descriptor starting point:
NOAEC
Value:
115 210 mg/m³
Explanation for the modification of the dose descriptor starting point:

No route to route extrapolation. In addition, the effects observed in the available studies of various durations (14, 28 or 90 days, developmental toxicity study) with the analogue substance considered of greater reactivity indicate no increased effects with time, but more concentration-driven effects (irritation and anaesthetic levels, or liver adaptative effects) that were associated with the highest concentrations.

Thus, no concentration-time correction is applied to the NOAEC in the DNEL derivation.

AF for dose response relationship:
1
Justification:
No adverse effect observed at this concentration
AF for differences in duration of exposure:
2
Justification:
From sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Not applicable when setting an inhalation DNEL based on an inhalation animal study
AF for other interspecies differences:
2.5
Justification:
Default value: Remaining differences
AF for intraspecies differences:
10
Justification:
General population
AF for the quality of the whole database:
1
Justification:
All studies were conducted following GLP procedures, K1
AF for remaining uncertainties:
1
Justification:
No other remaining differences
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:
no hazard identified
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

Basing on the analogue approach between GALDEN LMW and H GALDEN, as described in the appropriate sections and attachments of the dossier, it can be concluded that GALDEN LMW is expected to have the same toxicological profile as H GALDEN. The starting point NOAEC = 115210 mg/m³ derived from a 13 week inhalation toxicity study on H GALDEN is even considered a worst case approach because of the greater reactivity of H GALDEN in respect to GALDEN LMW. This consideration allows being on the safe side in regard to the potential hazard of GALDEN LMW following repeated dose exposure by inhalation

The NOAEC of 115210 mg/m3 is therefore used as the starting point for the derivation of long-term systemic inhalation DNEL value for the general population. No route to route extrapolation is needed. In addition, the effects observed in the available studies of various durations (14, 28 or 90 days, developmental toxicity study) with the analogue substance considered of greater reactivity indicate no increased effects with time, but more concentration-driven effects (irritation and anaesthetic levels, or liver adaptative effects) that were associated with the highest concentrations.

Thus, no concentration-time correction is applied to the NOAEC in the DNEL derivation.

GALDEN LMW is not classified for acute toxicity; acute systemic inhalation and acute dermal toxicity. Also, the skin sensitization test is negative. DNEL values are therefore not calculated, in the absence of any hazard.

The substance is not a skin or eye irritant; data available from acute inhalation toxicity study indicate that no respiratory irritation occurs. Local inhalation DNEL values are therefore not calculated.

 

There was no adverse effects observed in the 28-day oral toxicity study in rats with GALDEN LMW, at up to the limit dose of 1000 mg/kg/day. In addition, no exposure of the general population is expected by the oral route, and the substance is not classified for human health hazard. Thus no DNEL is necessary for the oral route.

No direct dermal exposure to the substance is expected for the general population. In addition prediction using the IH SkinPerm model indicate a very low absorption through the skin whether upon exposure to the liquid or via vapours.