Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6 074 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):
10
Modified dose descriptor starting point:
NOAEC
Value:
60 737 mg/m³
AF for dose response relationship:
1
Justification:
Not required, starting point is NOAEC.
AF for differences in duration of exposure:
2
Justification:
Extrapolation to chronic exposure based on a sub-chronic toxicity study.
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is not necessary for the inhalation route. Extrapolation is based on toxicological equivalence of a concentration of a chemical in the air of experimental animals and humans; animals and humans breathe at a rate depending on their caloric requirements.
AF for other interspecies differences:
1
Justification:
No additional interspecies factor is applied as:
- regarding toxicokinetics: no metabolic differences between rats and humans are expected for SF6 based on the substance chemical inertness and rapid excretion in unmetabolised form;
- regarding toxicodynamics: no effects were observed up to the relatively very high concentration of 120870 mg/m3. In addition, no differences are expected based on the chemical inertness of SF6.
AF for intraspecies differences:
5
Justification:
Default assessment factor for workers.
AF for the quality of the whole database:
1
Justification:
Database of appropriate quality
AF for remaining uncertainties:
1
Justification:
No remaining uncertainty 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

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

According to the REACH “Guidance on information requirements and chemical safety assessment”, a leading DN(M)EL needs to be derived for every relevant human population and every relevant route, duration and frequency of exposure, if feasible. As sulphur hexafluoride is a gas, oral and dermal routes of exposure are considered to be irrelevant, therefore no DNELs were derived for these routes.

As the substance is not classified for acute toxicity, according to the REACH “Guidance on information requirements and chemical safety assessment” (R.8.4.3.1), no acute / short-term exposure DNELs need to be derived.

For long-term exposure, data from a 90-day repeated dose toxicity study by the inhalation route is available. In this study, no adverse effects were observed in rats at the highest concentration tested (NOAEC of 120870 mg/m3, corresponding to a target limit concentration of 20000 ppm). This value will be used to derive a DNEL for long-term exposure. The substance is not genotoxic, not carcinogenic, and is not a reproductive or developmental toxicant. Therefore, no DNELs will be derived for these endpoints, i.e., the long-term DNEL is also considered sufficient to protect against these effects.

 

The DNEL for long-term exposure - local/systemic effects for workers is derived as follows:

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEC: 120870 mg/m3

The highest concentration in the subchronic toxicity study with rats; no adverse effects were observed.

Step 2) Modification of starting point

6/8

 

 

6.7 m3/10 m3

Correction of exposure duration in study (6 hrs/day, 5 days/week) to default worker exposure (8 hrs/day, 5 days/week);

 

Correction for activity driven differences of respiratory volumes in workers compared to workers in rest (6.7 m3/10 m3).

Step 3) Assessment factors

 

 

Interspecies

1

No additional interspecies factor is applied as:

- regarding toxicokinetics: no metabolic differences between rats and humans are expected for SF6 based on the substance chemical inertness and rapid excretion in unmetabolised form;

- regarding toxicodynamics: no effects were observed up to the relatively very high concentration of 120870 mg/m3. In addition, no differences are expected based on the chemical inertness of SF6.

Intraspecies

5

Default assessment factor

Exposure duration

2

Subchronic to chronic

Dose response

1

 

Quality of database

1

DNEL

Value

For workers

120870 x 6/8 x 6.7/10 / (1 x 5 x 2 x 1 x 1) = 6074 mg/m3 (1008 ppm)

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 511 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):
20
Modified dose descriptor starting point:
NOAEC
Value:
30 218 mg/m³
AF for dose response relationship:
1
Justification:
Not required, starting point is NOAEC.
AF for differences in duration of exposure:
2
Justification:
Extrapolation to chronic exposure based on a sub-chronic toxicity study.
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is not necessary for the inhalation route. Extrapolation is based on toxicological equivalence of a concentration of a chemical in the air of experimental animals and humans; animals and humans breathe at a rate depending on their caloric requirements.
AF for other interspecies differences:
1
Justification:
No additional interspecies factor is applied as:
- regarding toxicokinetics: no metabolic differences between rats and humans are expected for SF6 based on the substance chemical inertness and rapid excretion in unmetabolised form;
- regarding toxicodynamics: no effects were observed up to the relatively very high concentration of 120870 mg/m3. In addition, no differences are expected based on the chemical inertness of SF6.
AF for intraspecies differences:
10
Justification:
Default assessment factor for general population.
AF for the quality of the whole database:
1
Justification:
Database of appropriate quality,
AF for remaining uncertainties:
1
Justification:
No remaining uncertainty 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:
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

The DNEL for long-term exposure - systemic effects for the general population is derived as follows:

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEC: 120870 mg/m3

The highest concentration in the subacute toxicity study with rats; no adverse effects were observed

Step 2) Modification of starting point

6/24

 

 

Correction of exposure duration in study (6 hrs/day, 5 days/week) to default general population exposure (24 hrs/day) [1]

Step 3) Assessment factors

 

 

Interspecies

1

No additional interspecies factor is applied as:

- regarding toxicokinetics: no metabolic differences between rats and humans are expected for SF6 based on the substance chemical inertness and rapid excretion in unmetabolised form;

- regarding toxicodynamics: no effects were observed up to the relatively very high concentration of 120870 mg/m3. In addition, no differences are expected based on the chemical inertness of SF6.

Intraspecies

10

Default assessment factor for general population

Exposure duration

2

Subchronic to chronic

Dose response

1

 

Quality of database

1

DNEL

Value

For the general population

120870 x 6/24 / (1 x 10 x 2 x 1 x 1) = 1511 mg/m3 (250 ppm)

 [1] Exposure duration for humans indirect exposed via the environment is assumed 24 hours per day, for consumers the exposure duration is assumed 1-24 hours per day (depending on the exposure scenario).