Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.62 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
Modified dose descriptor starting point:
NOAEC
Value:
61.4 mg/m³
Explanation for the modification of the dose descriptor starting point:
The NOAEC is the concentration where no significant adverse effects were seen in a subchronic toxicity inhalation study in mice. Adjustments were applied for animal exposure as compared to worker exposure time (6 hr/8 hr), and to account for the increased respiratory volumes in active workers as compared to individuals at rest (6.7 m3/10 m3) per REACH guidance R.8.4.2. A factor of 1 was applied to route-to route extrapolation since the animal exposure was via inhalation.
AF for dose response relationship:
1
Justification:
The robust database supports the confidence in the dose descriptor.
AF for differences in duration of exposure:
2
Justification:
A factor to account for subchronic to chronic exposure was applied. Value adopted per REACH guidance R.8.4.3.1.
AF for interspecies differences (allometric scaling):
1
Justification:
A factor of 1 is appropriate since the adjusted start point was via mg/m3.
AF for other interspecies differences:
2.5
Justification:
A default factor of 2.5 is appropriate per REACH guidance R.8.4.3.1.
AF for intraspecies differences:
5
Justification:
This is a default assessment factor for workers per REACH Guidance R.8.4.3.1.
AF for the quality of the whole database:
2
Justification:
A high quality, reasonably robust toxicity database exists for this substance. However, to account for the lack of a carcinogenicity test, a factor of 2 was applied.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
46 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
Modified dose descriptor starting point:
NOAEC
Value:
859 mg/m³
Explanation for the modification of the dose descriptor starting point:
The NOAEC is the concentration where no significant adverse effects were seen in an acute toxicity inhalation study in rats. Adjustment was applied to account for the increased respiratory volumes in active workers as compared to individuals at rest (6.7 m3/10 m3) per REACH guidance R.8.4.2. A factor of 1 was applied to route-to route extrapolation since the animal exposure was via inhalation.
AF for dose response relationship:
1
Justification:
The robust database supports the confidence in the dose descriptor.
AF for interspecies differences (allometric scaling):
1
Justification:
A factor of 1 is appropriate since the adjusted start point was via mg/m3.
AF for other interspecies differences:
2.5
Justification:
A default factor of 2.5 is appropriate per REACH guidance R.8.4.3.1.
AF for intraspecies differences:
5
Justification:
This is a default assessment factor for workers per REACH Guidance R.8.4.3.1.
AF for the quality of the whole database:
1
Justification:
High quality acute inhalation data exists for this substance.
AF for remaining uncertainties:
1
Justification:
Exposure duration: A factor of 1 is appropriate since the acute inhalation study exceeded the exposure time associated with the acute inhalation worker DNEL.

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:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
hazard unknown (no further information necessary)

Additional information - workers

This is a volatile substance and potential worker exposure would likely occur via the inhalation route. Therefore, no worker oral or dermal route DNELs were derived.

 

No local effects were observed in acute or repeated exposure studies; therefore no DNEL for local effects was derived.

Worker Long-Term Inhalation:

The substance is classified as Acute Toxicity Category 4 (Harmful if inhaled) and Specific Target Organ Toxicity – Single Exposure Category 2 (May cause damage to kidneys if inhaled), Specific Target Organ Toxicity – Single Exposure Category 3 (may cause respiratory irritation) and Specific Target Organ Toxicity Repeated Exposure Category 2 (Kidney) according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

The rat 4-hr inhalation LC50 is 3060 ppm (18776 mg/m3). The NOAEL for systemic toxicity effects after 90 days of inhalation exposure in mice is 10 ppm (61.4 mg/m3). At concentrations of approximately 50 ppm and greater, adverse kidney effects were observed. The substance was not mutagenic and did not produce damage to genetic material. Based on this information, the NOAEL for significant effects was determined to be 10 ppm (61.4 mg/m3).

 

Worker Acute (15 -Minute) Inhalation:

Rats were exposed via whole-body inhalation to 140, 320, 690, 1090, 1520, 1980, 2220, 2520, 2600, 2870, 3020 or 3440 ppm HFP for 4 hours. The 4-hour inhalation LC50 for rats was found to be 3060 ppm. A pathological exam was conducted at the end of the post-exposure period. Kidney morphology effects (healing nephrosis) and kidney function effects were seen at 320 ppm and higher. The observed effects from 320 ppm to 2600 were predominantly healing (reversible) nephrosis. However, at concentrations of 2870 and higher, kidney effects were identified as nephrosis without evidence of reversibility. The lowest level at which an effect was observed was 320 ppm. At 140 ppm, (859 mg/m3) the rats appeared normal in all respects.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.15 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):
100
Modified dose descriptor starting point:
NOAEC
Value:
61.4 mg/m³
Explanation for the modification of the dose descriptor starting point:
The NOAEC is the concentration where no significant adverse effects were seen in a subchronic toxicity inhalation study in mice. Adjustment was applied for animal exposure as compared to general population exposure time (6 hr/24 hr) per REACH guidance R.8.4.2. A factor of 1 was applied to route-to route extrapolation since the animal exposure was via inhalation.
AF for dose response relationship:
1
Justification:
The robust database supports the confidence in the dose descriptor.
AF for differences in duration of exposure:
2
Justification:
A factor to account for subchronic to chronic inhalation exposure was applied. Value adopted per REACH guidance R.8.4.3.1
AF for interspecies differences (allometric scaling):
1
Justification:
A factor of 1 is appropriate since the adjusted start point was via mg/m3.
AF for other interspecies differences:
2.5
Justification:
A default factor of 2.5 is appropriate per REACH guidance R.8.4.3.1.
AF for intraspecies differences:
10
Justification:
This is a default assessment factor for general population per REACH Guidance R.8.4.3.1.
AF for the quality of the whole database:
2
Justification:
A high quality, reasonably robust toxicity database exists for this substance. However, to account for the lack of a carcinogenicity test, a factor of 2 was applied.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
34 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):
25
Modified dose descriptor starting point:
NOAEC
Value:
859 mg/m³
Explanation for the modification of the dose descriptor starting point:
The NOAEC is the concentration where no significant adverse effects were seen in an acute toxicity inhalation study in rats. A factor of 1 was applied to route-to route extrapolation since the animal exposure was via inhalation.
AF for dose response relationship:
1
Justification:
The robust database supports the confidence in the dose descriptor
AF for interspecies differences (allometric scaling):
1
Justification:
A factor of 1 is appropriate since the adjusted start point was via mg/m3.
AF for other interspecies differences:
2.5
Justification:
A default factor of 2.5 is appropriate per REACH guidance R.8.4.3.1.
AF for intraspecies differences:
10
Justification:
This is a default assessment factor for general population per REACH Guidance R.8.4.3.1.
AF for the quality of the whole database:
1
Justification:
High quality acute inhalation data exists for this substance.
AF for remaining uncertainties:
1
Justification:
Exposure duration:A factor of 1 is appropriate since the acute inhalation study exceeded the exposure time associated with the acute inhalation general population DNEL.

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:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
hazard unknown (no further information necessary)

Additional information - General Population

This is a volatile substance and potential worker exposure would likely occur via the inhalation route. Therefore, no general population oral or dermal route DNELs were derived.

 

No local effects were observed in acute or repeated exposure studies; therefore no DNEL for local effects was derived.

General Population Long-Term Inhalation:

The substance is classified as Acute Toxicity Category 4 (Harmful if inhaled) and Specific Target Organ Toxicity – Single Exposure Category 2 (May cause damage to kidneys if inhaled), Specific Target Organ Toxicity – Single Exposure Category 3 (may cause respiratory irritation) and Specific Target Organ Toxicity Repeated Exposure Category 2 (Kidney) according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

The rat 4-hr inhalation LC50 is 3060 ppm (18776 mg/m3). The NOAEL for systemic toxicity effects after 90 days of inhalation exposure in mice is 10 ppm (61.4 mg/m3). At concentrations of approximately 50 ppm and greater, adverse kidney effects were observed. The substance was not mutagenic and did not produce damage to genetic material. Based on this information, the NOAEL for significant effects was determined to be 10 ppm (61.4 mg/m3).

 

Genera Population Acute (15 -Minute) Inhalation:

Rats were exposed via whole-body inhalation to 140, 320, 690, 1090, 1520, 1980, 2220, 2520, 2600, 2870, 3020 or 3440 ppm HFP for 4 hours. The 4-hour inhalation LC50 for rats was found to be 3060 ppm. A pathological exam was conducted at the end of the post-exposure period. Kidney morphology effects (healing nephrosis) and kidney function effects were seen at 320 ppm and higher. The observed effects from 320 ppm to 2600 were predominantly healing (reversible) nephrosis. However, at concentrations of 2870 and higher, kidney effects were identified as nephrosis without evidence of reversibility. The lowest level at which an effect was observed was 320 ppm. At 140 ppm, (859 mg/m3) the rats appeared normal in all respects.