Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
16 444 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
7.5
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

The DNEL for workers was derived in accordance to the ECHA REACH Guidance on information requirements and chemical safety assessment (R.8).

In view of the toxicological and physicochemical properties of HFC 125, the dermal exposure was considered as not relevant for workers and DNEL derivation was limited to the exposure by inhalation.

In view of the absence of acute toxicity far beyond the threshold criteria for classification, the derivation of an acute DNEL is not deemed as necessary.

As no indication of local effects was observed for HFC-125, the long term exposure DNEL was derived for systemic effects only.

The NOAEC of 245440 mg/m3, derived from a subchronic toxicity study in rats was taken as the most relevant dose descriptors for the derivation of the long term DNEL. The relevant default modification and assessment factors indicated by the REACH guidance were applied to the selected dose descriptor:

Modifying factors

- 6/8 was considered to address the differences in the daily exposure duration (6 h/day in the subchronic study vs 8 h/day of occupational exposure).

- 6.7/10 m3 was considered to address the different respiratory volumes between human in rest and workers under light work activity

Assessment factors:

- 2.5 was taken to address the interspecies extrapolation (toxicodynamic differences).

- 3 was considered to address the intraspecies extrapolation (worker subpopulation). As effects were observed at the highest tested concentration (50000 ppm v/v). An intraspecies AF of 3 is considered as amply sufficient.

- 1 was considered to address the exposure duration extrapolation (from subchronic to chronic exposure). HFC 125 showed no adverse effects at the highest tested concentration (50000 ppm v/v) both in a subacute and subchronic study in rats. No dependence on exposure duration is observable. The AF is not considered necessary.

- 1 was considered to address the dose-response relationship.

- 1 was considered to address the quality of the database.

The corrected NOAEC can be calculated by applying the reported modifying factors: Corrected NOAEC = 245440 x (6/8 x 6.7/10) = 123330 mg/m3 Overall, the DNEL for long term occupational exposure by inhalation is calculated by dividing the corrected NOAEC for the assessment factors:

DNEL = 123330 /(2.5 x 3 x 1 x 1 x 1) = 16444 mg/m3 (3350 ppm v/v)

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 753 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
25
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

The DNEL for general population were derived in accordance to the ECHA REACH Guidance on information requirements and chemical safety assessment (R.8).

In view of the toxicological and physicochemical properties of HFC 125, the dermal and oral routes of exposure were considered as not relevant and DNEL derivation was limited to the exposure by inhalation.

In view of the absence of acute toxicity far beyond the threshold criteria for classification, the derivation of an acute DNEL is not deemed as necessary.

As no indication of local effects was observed for HFC-125, the long term exposure DNEL was derived for systemic effects only.

The NOAEC of 245440 mg/m3, derived from a subchronic toxicity study in rats was taken as the most relevant dose descriptors for the derivation of the long term DNEL. The relevant default modification and assessment factors indicated by the REACH guidance were applied to the selected dose descriptor:

Modifying factors

- 6/24 was considered to address the differences in the daily exposure duration (6 h/day in the subchronic study vs 24 h/day of exposure for general population).

- 5/7 was considered to address the different exposure conditions (5 days/week in the subchronic study, 7 days/week of exposure for general population)

Assessment factors:

- 2.5 was taken to address the interspecies extrapolation (toxicodynamic differences).

- 10 was considered to address the intraspecies extrapolation (General population).

- 1 was considered to address the exposure duration extrapolation (from subchronic to chronic exposure).HFC 125 showed no adverse effects at the highest tested concentration (50000 ppm v/v) both in a subacute and subchronic study in rats. No dependence on exposure duration is observable. The AF is not considered necessary.

- 1 was considered to address the dose-response relationship.

- 1 was considered to address the quality of the database.

The corrected NOAEC can be calculated by applying the reported modifying factors:

Corrected NOAEC = 245440 x (6/24 x 5/7) = 43829 mg/m3

Overall, the DNEL for long term occupational exposure by inhalation is calculated by dividing the corrected NOAEC for the assessment factors:

DNEL = 43,829 /(2.5 x 10 x 1 x 1 x 1) = 1753 mg/m3