Registration Dossier

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 260 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
Modified dose descriptor starting point:
NOAEC
Value:
1 260 mg/m³
Explanation for the modification of the dose descriptor starting point:

Corrected NOAEC = 62,671 x 6/8 x 6.7/10 = 31,492 mg/m3

Overall, the DNEL for long-term occupational exposure by inhalation is calculated by dividing the corrected NOAEC by the assessment factors (AF):

DNEL (long-term effects in workers) = 31,492 / (2.5 x 5 x 2 x 1 x 1) =1,260 mg/m3=207 ppm

AF for dose response relationship:
1
Justification:
A factor of 1 addresses dose response.
AF for differences in duration of exposure:
2
Justification:
A factor of 2 is considered appropriate for exposure duration as the starting point is the NOAEC from a 90-day study.
AF for interspecies differences (allometric scaling):
2.5
Justification:
2.5 was used to address the interspecies extrapolation (toxicodynamic differences)
AF for intraspecies differences:
5
Justification:
5 was considered appropriate to address the intraspecies extrapolation (worker sub-population).
AF for the quality of the whole database:
1
Justification:
A factor of 1 is considered appropriate for the quality of the database.
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
69 365 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:
69 365 mg/m³
Explanation for the modification of the dose descriptor starting point:

Corrected NOAEC = 1,294,114 x 6.7/10 = 867,056 mg/m3

Overall, the DNEL for systemic effects following acute occupational exposure by inhalation is calculated by dividing the corrected NOAEC by the assessment factors (AF):

DNEL (long-term effects in workers) =867,056 /(2.5 x 5 x 1 x 1 x 1) =69,365 mg/m³ = 11,422 ppm

AF for dose response relationship:
1
Justification:
A factor of 1 addresses dose response.
AF for interspecies differences (allometric scaling):
2.5
Justification:
2.5 was used to address the interspecies extrapolation (toxicodynamic differences)
AF for other interspecies differences:
1
AF for intraspecies differences:
5
Justification:
5 was considered appropriate to address the intraspecies extrapolation (worker sub-population).
AF for the quality of the whole database:
1
Justification:
A factor of 1 is considered appropriate for the quality of the database.
AF for remaining uncertainties:
1

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 HCFO 1224(yd)Z is a gas, the oral and dermal routes of exposure are considered to be not relevant, therefore no DNELs were derived for these routes.

Inhalation studies have shown HCFO 1224yd(Z) to be of an extremely low order of acute toxicity, with the 4 hour LC50 in the rat found to be in excess of 213,100ppm (1,294,114 mg/m3). However, symptoms of CNS depression were seen in rats exposed at this concentration for 4 hours. The substance is classified as STOT SE3 (H336 May cause drowsiness and dizziness). A DNEL has been derived to take account of this hazard.

 

Exposure of male rats to HCFO 1224yd(Z)at 20,720 ppm (125,828 mg/m3) for 90 days resulted in lower weights of the epididymides and histological alterations in the testes (atrophy of seminiferous tubule). The NOAEC for the effects was 10,320 ppm(62,671 mg/m3). A DNEL has been derived to take account of this hazard.

As no local effects were observed in either acute or long-term exposure studies, no DNELs for local effects were derived.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
224 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:
224 mg/m³
Explanation for the modification of the dose descriptor starting point:

Corrected NOAEC = 62,671 x 6/24 x 5/7 = 11,191 mg/m3

Overall, the DNEL for long-term occupational exposure by inhalation is calculated by dividing the corrected NOAEC by the assessment factors (AF):

DNEL (long-term effects in the general population) = 11,191 / (2.5 x 10 x 2 x 1 x 1) =224 mg/m3=37 ppm

AF for dose response relationship:
1
Justification:
A factor of 1 addresses dose response.
AF for differences in duration of exposure:
2
Justification:
A factor of 2 is considered appropriate for exposure duration as the starting point is the NOAEC from a 90-day study.
AF for interspecies differences (allometric scaling):
2.5
Justification:
2.5 was used to address the interspecies extrapolation (toxicodynamic differences)
AF for other interspecies differences:
1
AF for intraspecies differences:
10
Justification:
10 was considered appropriate to address the intraspecies extrapolation (general population)
AF for the quality of the whole database:
1
Justification:
A factor of 1 is considered appropriate for the quality of the database.
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
51 765 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
Modified dose descriptor starting point:
NOAEC
Value:
51 765 mg/m³
Explanation for the modification of the dose descriptor starting point:

No correction to the NOAEC is required to take account of differences in activity.

Overall, the DNEL for systemic effects following acute occupational exposure by inhalation is calculated by dividing the corrected NOAEC by the assessment factors (AF):

DNEL (long-term effects in the general population) = 1,294,114 /(2.5 x 10 x 1 x 1 x 1) =51,765 mg/m³ = 8,524 ppm

AF for dose response relationship:
1
Justification:
A factor of 1 addresses dose response.
AF for interspecies differences (allometric scaling):
2.5
Justification:
2.5 was used to address the interspecies extrapolation (toxicodynamic differences)
AF for other interspecies differences:
1
AF for intraspecies differences:
10
Justification:
10 was considered appropriate to address the intraspecies extrapolation (general population).
AF for the quality of the whole database:
1
Justification:
A factor of 1 is considered appropriate for the quality of the database.
AF for remaining uncertainties:
1

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

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 HCFO 1224(yd)Z is a gas, the oral and dermal routes of exposure are considered to be not relevant, therefore no DNELs were derived for these routes.

Inhalation studies have shown HCFO 1224yd(Z) to be of an extremely low order of acute toxicity, with the 4 hour LC50 in the rat found to be in excess of 213,100ppm (1,294,114 mg/m3). However, symptoms of CNS depression were seen in rats exposed at this concentration for 4 hours. The substance is classified as STOT SE3 (H336 May cause drowsiness and dizziness). A DNEL has been derived to take account of this hazard.

 

Exposure of male rats to HCFO 1224yd(Z)at 20,720 ppm (125,828 mg/m3)for 90 days resulted in lower weights of the epididymides and histological alterations in the testes (atrophy of seminiferous tubule). The NOAEC for the effects was 10,320 ppm(62,671 mg/m3). A DNEL has been derived to take account of this hazard.

As no local effects were observed in either acute or long-term exposure studies, no DNELs for local effects were derived.