Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 656.6 mg/m³
Most sensitive endpoint:
carcinogenicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
5
Modified dose descriptor starting point:
NOAEC
Value:
8 283.2 mg/m³
Explanation for the modification of the dose descriptor starting point:
Inhalation to inhalation
AF for dose response relationship:
1
Justification:
NOAEC available
AF for differences in duration of exposure:
1
Justification:
Chronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling per REACH R.8.4.3.1 (inhalation)
AF for other interspecies differences:
1
Justification:
Mechanistic and comparative metabolism data show that humans likely to be less sensitive to the effects of CFC-12 than rats and mice and are unlikely to be more sensitive.
AF for intraspecies differences:
5
Justification:
A default assesment factor for workers, as proposed in the REACH Guidance (R 8.4.3.1)
AF for the quality of the whole database:
1
Justification:
General assignment, long term studies available.
AF for remaining uncertainties:
1
Justification:
Route to route extrapolation; Inhalation to inhalation
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

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 the substance is a gas, oral and dermal routes of exposure are considered to be irrelevant, therefore no DNELs were derived for these routes. The substance is not classified for acute toxicity, and according to REACH "Guidance on information requirements and chemical safety assessment" (R.8.4.3.1), no acute/short term exposure DNELs need to be derived.

A NOAEC can be derived for carcinogenic effects in the 2 year study in rats and mice since no effects were observed in the study. A DNEL for CFC-12 can be derived using the NOAEC:5000 ppm = 2.4726e+4 mg/m3 in the rat as the starting point and using the default approach proposed in the ECHA Guidance.

Calculation of DNEL for long-term exposure - carcinogenic / systemic effects in workers is derived as follows:

Description

Value

Remark

Relevant dose descriptor

Corrected NOAEC 8283.2 mg/m3 (1675.0 ppm)

NOAEC:5000 ppm = 2.4726e+4 mg/m3

Correct for respiratory volume (from resting rat to active human): 6.7 m3/10m3 = 0.67. Correct for exposure time (from 4 hour rat to 8 hour human): 4/8 = 0.5 Corrected NOAEC =2.4726e+4 x 0.67 x 0.5 = 8283.2 mg/m3 (1675.0 ppm)

Route to route extrapolation

1

Inhalation to inhalation

Scaling factor animal to man

1

No allometric scaling per REACH R.8.4.3.1 (inhalation)

Other interspecies differences

1

Mechanistic and comparative metabolism data show that humans likely to be less sensitive to the effects of CFC-12 than rats and mice and are unlikely to be more sensitive.

Intraspecies variability

5

A default assesment factor for workers, as proposed in the REACH Guidance (R 8.4.3.1)

Exposure duration

1

Chronic to chronic

Dose response

1

NOAEL available

Quality of the database

1

General assignment, long term studies available.

DNEL

Value

For workers

8283.2 / (1 x 1 x 1 x 5 x 1 x 1 x 1) =1656.6 mg/m3 = 334.97 ppm

 

The worker DNEL value derived for chronic exposure would have to be adapted in case of a different shift system (= daily exposure time). In that case the amended DNEL would result in virtually the same value under the condition that the weekly exposure time would be almost identical.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
420.34 mg/m³
Most sensitive endpoint:
carcinogenicity
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:
4 203.42 mg/m³
Explanation for the modification of the dose descriptor starting point:
Inhalation to inhalation.
AF for dose response relationship:
1
Justification:
NOAEC available
AF for differences in duration of exposure:
1
Justification:
Chronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling per REACH R.8.4.3.1 (inhalation)
AF for other interspecies differences:
1
Justification:
Mechanistic and comparative metabolism studies show that humans likely to be less sensitive to the effects of CFC-12 than rats and mice and are unlikely to be more sensitive.
AF for intraspecies differences:
10
Justification:
A default assesment factor for the general population, as proposed in the REACH Guidance (R 8.4.3.1)
AF for the quality of the whole database:
1
Justification:
General assignment, long term studies available.
AF for remaining uncertainties:
1
Justification:
Route to route extrapolation; Inhalation to inhalation
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

General population

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 the substance is a gas, oral and dermal routes of exposure are considered to be irrelevant, therefore no DNELs were derived for these routes. The substance is not classified for acute toxicity, and according to REACH "Guidance on information requirements and chemical safety assessment" (R.8.4.3.1), no acute/short term exposure DNELs need to be derived.

It should be noted that CFC-12 is not available to the general population, due to its ban in accordance with the Montreal Protocol. It is no longer used as a propellant in aerosols, and hence exposure is not relevant. However, this data is included for completeness purposes.

A NOAEC can be derived for carcinogenic effects in the 2 year study in rats and mice since no effects were observed in the study. A DNEL for CFC-12 can be derived using the NOAEC:5000 ppm = 2.4726e+4 mg/m3 in the rat as the starting point and using the default approach proposed in the ECHA Guidance.

Calculation of DNEL for long-term exposure - carcinogenic / systemic effects in the general population is derived as follows:

Description

Value

Remark

Relevant dose descriptor

Corrected NOAEC 4203.42 mg/m3 (850 ppm)

NOAEC:5000 ppm = 2.4726e+4 mg/m3

Correct for exposure time (from 4 hour rat to 24 hour human): 4/24 = 0.17.(ECHA Guidance Chapter R.8 (fig. R.8-2)).

Corrected LOAEL =2.4726e+4x 0.17 = 4203.42 mg/m3 (850 ppm)

Route to route extrapolation

1

Inhalation to inhalation

Scaling factor animal to man

1

No allometric scaling per REACH R.8.4.3.1 (inhalation)

Other interspecies differences

1

Mechanistic and comparative metabolism studies show Mechanistic and comparative metabolism studies show that humans likely to be less sensitive to the effects of CFC-12 than rats and mice and are unlikely to be more sensitive.

Intraspecies variability

10

A default assessment factor for the general population, as proposed in the REACH Guidance (R 8.4.3.1)

Exposure duration

1

Chronic to chronic

Dose response

1

NOAEL available

Quality of the database

1

General assignment, long term studies available.

DNEL

Value

For general population

4203.42/ (1 x 1 x 1 x 10 x 1 x 1 x 1) =420.34 mg/m3 = 84.90 ppm