Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
67.4 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):
150
Modified dose descriptor starting point:
NOAEC
DNEL value:
10 122 mg/m³
Explanation for the modification of the dose descriptor starting point:
inhalation to inhalation
AF for dose response relationship:
1
Justification:
a NOAEC is observed
AF for differences in duration of exposure:
6
Justification:
Sub-acute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling per REACH
AF for other interspecies differences:
2.5
Justification:
Default toxicodynamic differences REACH Guidance (R 8.4.3.1)
AF for intraspecies differences:
5
Justification:
A default assessment factor for workers proposed in the REACH Guidance (R 8.4.3.1)
AF for the quality of the whole database:
2
Justification:
Developmental toxicity data available but no fertility data. No two-generation reproductive toxicity study.
AF for remaining uncertainties:
1
Justification:
No further assessment factor judged necessary.
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

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. The oral and dermal routes of exposure are considered to be unlikely routes of exposure for PFBE, 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 DNEL for PFBE can be derived using the clear NOAEC of 20123 mg/m3 (2000 ppm) demonstrated in the 28-day repeat dose toxicity study in the rat.

PFBE Table A. Calculation of DNEL for long-term exposure - systemic effects in workers is derived as follows:

 Description

 Value

 Remark

 Relevant dose descriptor

 Corrected NOAEC 10112 mg/m3 (1005 ppm)

Correct for respiratory volume (from resting rat to active human): 6.7 m3/10m3 = 0.67. Correct for exposure time (from 6 hour rat to 8 hour human): 6/8 = 0.75 Corrected NOAEC = 20123 x 0.67 x 0.75 = 10112 mg/m3 (1005 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

 Other interspecies differences

 2.5

Default toxicodynamic differences REACH Guidance R8. Appendix 3

 Intraspecies variability

 5

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

 Exposure duration

 6

 Sub-acute to chronic.

A default assessment factor. REACH Guidance R8. Appendix 3. Also see Reference (a)

 Dose response

 1

 A NOAEC is observed

 Quality of the database

 2

 Developmental toxicity data but no fertility data. No two-generation reproductive toxicity study.

 DNEL

 Value

 

For workers

 

10112/ (1 x 1 x 2.5 x 5 x 6 x 1 x 2) =67.4 mg/m3

PFBE DNEL for workers (based on ECHA Guidance = 67.4 mg/m3 (6.7 ppm)

 

(a) Principles for deriving 'Provisional Workplace Guidance Values' (Arbeitsplatzrichtwerte, ARW) for airborne substances by the German Committee on Hazardous Substances (Ausschuss für Gefahrstoffe). Cited by Kalberlah F et al Ann. occup. Hyg., Vol 46, No.2, pp 175 - 185, 2002.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
16.8 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):
300
Modified dose descriptor starting point:
NOAEC
DNEL value:
5 031 mg/m³
Explanation for the modification of the dose descriptor starting point:
Inhalation to inhalation
AF for dose response relationship:
1
Justification:
A NOAEC is observed
AF for differences in duration of exposure:
6
Justification:
Sub-acute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling per REACH 8.4.3.1
AF for other interspecies differences:
2.5
Justification:
Default toxicodynamic differences REACH Guidance R8. Appendix 3.
AF for intraspecies differences:
10
Justification:
A default assessment factor for the general population, as proposed in the REACH Guidance (R8.4.3.1)
AF for the quality of the whole database:
2
Justification:
Developmental toxicity data but no fertility data. No two-generation reproductive toxicity study.
AF for remaining uncertainties:
1
Justification:
No further assessment factor judged necessary
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

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. The oral and dermal routes of exposure are considered to be unlikely routes of exposure for PFBE, 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 DNEL for PFBE can be derived using the clear NOAEC of 20123 mg/m3 (2000 ppm) demonstrated in the 28-day repeat dose toxicity study in the rat.

PFBE Table B. Calculation of DNEL for long-term exposure - systemic effects in the general population is derived as follows:

 

 Description

 Value

 Remark

 Relevant dose descriptor

 Corrected NOAEC 5031 mg/m3 (500 ppm)

Correct for exposure time (from 6 hour rat to 24 hour human): 6/24 = 0.25.

Corrected NOAEC = 20123 x 0.25 = 5031 mg/m3 (500 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

 Other interspecies differences

 2.5

Default toxicodynamic differences REACH Guidance R8. Appendix 3

 Intraspecies variability

 10

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

 Exposure duration

 6

 Sub-acute to chronic.

A default assessment factor. REACH Guidance R8. Appendix 3. Also see Reference (a)

 Dose response

 1

 A NOAEC is observed

 Quality of the database

 2

 Developmental toxicity data but no fertility data. No two-generation reproductive toxicity study.

 DNEL

 Value

 

For general population

 

5031 / (1 x 1 x 2.5 x 10 x 6 x 1 x 2) =16.8 mg/m3

PFBE DNEL for general population (based on ECHA Guidance = 16.8 mg/m3 (1.7 ppm)

 

(a) Principles for deriving 'Provisional Workplace Guidance Values' (Arbeitsplatzrichtwerte, ARW) for airborne substances by the German Committee on Hazardous Substances (Ausschuss für Gefahrstoffe). Cited by Kalberlah F et al Ann. occup. Hyg., Vol 46, No.2, pp 175 - 185, 2002.