Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.77 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
DNEL value:
138.14 mg/m³
Modified dose descriptor starting point:
NOAEC
DNEL value:
69.42 mg/m³
Explanation for the modification of the dose descriptor starting point:

According to ECHA REACH Guidance R.8. methodology, the dose descriptor starting point (NOAEC, rat) is corrected for taking into account:

- Differences in human and experimental exposure conditions (8 hours/day exposure for workers vs 6 hours/day exposure for rat).

- Differences in respiratory volumes between experimental animals (at rest) and workers (light activity)

Corrected NAEC (human) = 138.14 mg/m3 (NOAEC rat) x 6.7 m 3 / 10 m 3 x 6 (h/d) / 8 (h/d) = 69.42 mg/m3

Where:

6.7 m3: respiratory volume during no physical activity

10 m3: respiratory volume during light physical activity

6 h/day: exposure duration rat

8 h/day: exposure duration workers

AF for dose response relationship:
1
Justification:
The starting point is a NOAEC / Data support the confidence in the dose descriptor.
AF for differences in duration of exposure:
2
Justification:
The NOAEC was derived from a sub-chronic test. Default AF according to REACH guidance R.8.4.3.1
AF for interspecies differences (allometric scaling):
1
Justification:
A factor of 1 is appropriate since the adjusted starting point was in mg/m3
AF for other interspecies differences:
2.5
Justification:
Default AF according to REACH guidance R.8.4.3.1
AF for intraspecies differences:
5
Justification:
Default AF for workers according to REACH guidance R.8.4.3.1
AF for the quality of the whole database:
1
Justification:
CTFE was tested by inhalation for subacute and subchronic toxicity in several studies and on several species.
The selected key study was valid and reliable. Results of the key study are supported by consistent findings observed in other subacute and subchronic studies conducted on rat.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
65.62 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12.5
Dose descriptor starting point:
NOAEC
DNEL value:
485.89 mg/m³
Modified dose descriptor starting point:
NOAEC
DNEL value:
820.31 mg/m³
Explanation for the modification of the dose descriptor starting point:

According to ECHA REACH Guidance R.8. methodology, the dose descriptor starting point (NOAEC, rat) is corrected for taking into account differences in respiratory volumes between experimental animals (at rest) and workers (light activity):

NAEC (4h, human) = 485.89 mg / m3 (NOAEC, 4h rat) x 6.7 m3/ 10 m3= 325.54 mg/m3

Where:

6.7 m3: respiratory volume during no physical activity

10 m3: respiratory volume during light physical activity

The corrected dose descriptor for the exposure duration of 15 minutes is extrapolated from the NAEC (4h, human) by the mean of the modified Haber’s equation (ECHA Guidance R.8). The use of the Haber’s equation is considered valid as the acute toxic effects of CTFE are observed to be dose related. Being no data available for CTFE on concentration-time ratio for exposure time shorted than 3 hour, the modified Haber’s law: Cnx t = k is applied with a default n=3 (ECHA Guidance R.8).

 

NAEC (15 min, human) = [NAEC (4h, human)3x 4h / 15 min ] 1/3 = [ 325.543x 4 / 0.25 ] 1/3 = 820.31 mg/m3

AF for dose response relationship:
1
Justification:
The starting point is a NOAEC.
AF for interspecies differences (allometric scaling):
1
Justification:
A factor of 1 is appropriate since the adjusted starting point is in mg/m3
AF for other interspecies differences:
2.5
Justification:
Default AF according to REACH guidance R.8.4.3.1
AF for intraspecies differences:
5
Justification:
Default AF for workers according to REACH guidance R.8.4.3.1
AF for the quality of the whole database:
1
Justification:
Several acute toxicity studies (K2 or K4) through the inhalation route are available, performed on several species (rat, mouse, guinea pig, rabbit, dog).
The dose descriptor starting point derives form a reliable study (K2) conducted on the preferred species (rat).
Key and supporting studies provide consistent information.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.

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

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.69 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
DNEL value:
138.14 mg/m³
Modified dose descriptor starting point:
NOAEC
DNEL value:
34.535 mg/m³
Explanation for the modification of the dose descriptor starting point:

According to ECHA REACH Guidance R.8. methodology, the dose descriptor starting point (NOAEC, rat) is corrected for taking into account: differences in human and experimental exposure conditions (24 hours/day exposure for general population vs 6 hours/day exposure for rat).

Corrected NAEC (human) = 138.14 mg/m3 (NOAEC rat) x 6 h/d / 24 h/d = 34.535 mg/m3

AF for dose response relationship:
1
Justification:
The starting point is a NOAEC / Data support the confidence in the dose descriptor.
AF for differences in duration of exposure:
2
Justification:
The NOAEC was derived from a sub-chronic test. Default AF according to REACH guidance R.8.4.3.1
AF for interspecies differences (allometric scaling):
1
Justification:
A factor of 1 is appropriate since the adjusted starting point was in mg/m3
AF for other interspecies differences:
2.5
Justification:
Default AF for workers according to REACH guidance R.8.4.3.1
AF for intraspecies differences:
10
Justification:
Default AF for workers according to REACH guidance R.8.4.3.1
AF for the quality of the whole database:
1
Justification:
CTFE was tested by inhalation for subacute and subchronic toxicity in several studies and on several
species.
The selected key study was valid and reliable. Results of the key study are supported by consistent findings observed in other subacute and subchronic studies conducted on rat.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
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