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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.53 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
30
Dose descriptor starting point:
NOAEL
Value:
120 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
105.8 mg/m³
Explanation for the modification of the dose descriptor starting point:

Strating point: NOAEL for reproductive and developmental toxicity in female rats given THFMA by oral gavage in an OECD 422 protocol

Modification of starting point involves conversion of rat oral exposure to human inhalation exposure using ECHA Ch R8, Fig. 8.3. Human NOAEC = Oral NOAEL X 1/0.38 m³/kg/d X 0.5 absn. Default X 6.7/10 = 105.8 mg/m³

AF for dose response relationship:
1
Justification:
The NOAEC is reliable. No adjustment is required.
AF for differences in duration of exposure:
6
Justification:
The key studies were subacute toxicity studies in animals which require extrapolation to a working lifetime in humans using ECHA Ch R8, Table R. 8-5.
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling factor of 4 is not necessary because conversion is from rat oral to human inhalation (Ch R8. p.30)
AF for other interspecies differences:
1
Justification:
Remaining differences factor of 2.5 (Ch R8 p.29/30) is not required due to rapid metabolism of the parent ester to the alcohol and MAA so no TD differences between rats and humans are expected.
AF for intraspecies differences:
5
Justification:
A combined interspecies and intraspecies assessment factor of 5 is using ECHA Ch R8, Characterisation of dose [concentration]-response for human health - Intraspecies differences, page 36.
AF for the quality of the whole database:
1
Justification:
The key studies were of high quality. No adjustment is required.
AF for remaining uncertainties:
1
Justification:
The duration factor of 6 is sufficient to address the limited sensitivity of the screening study.
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
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
120
Dose descriptor starting point:
NOAEL
Value:
120 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
120 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Starting point: NOAEL for reproductive and developmental toxicity in female rats given THFMA by oral gavage in an OECD 422 protocol

Modification of starting point involves conversion of rat oral exposure to human dermal exposure using ECHA Ch R8, Ex. B5, page 69. Human NOAEL = Oral NOAEL X 1 (Absorption factor for oral to dermal route =1; ECHA Ch R8. page 25.)

AF for dose response relationship:
1
Justification:
The NOAEL is reliable. No adjustment is required.
AF for differences in duration of exposure:
6
Justification:
The key studies were subacute toxicity studies in animals which require extrapolation to a working lifetime in humans using ECHA Ch R8, Table R. 8-5.
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling factor of 4 is applied for conversion from rat oral to human dermal exposure (Ch R8. p.30)
AF for other interspecies differences:
1
Justification:
Remaining differences factor of 2.5 (Ch R8 p.29/30) is not required to rapid metabolism of the parent ester to the alcohol and MAA so no TD differences between rats and humans are expected.
AF for intraspecies differences:
5
Justification:
A combined interspecies and intraspecies assessment factor of 5 is using ECHA Ch R8, Characterisation of dose [concentration]-response for human health - Intraspecies differences, page 36.
AF for the quality of the whole database:
1
Justification:
The key studies were of high quality. No adjustment is required.
AF for remaining uncertainties:
1
Justification:
The duration factor of 6 is sufficient to address the limited sensitivity of the screening study.
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:
0.87 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
60
Dose descriptor starting point:
NOAEL
Value:
120 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
52.17 mg/m³
Explanation for the modification of the dose descriptor starting point:

Modification of starting point involves conversion of rat oral exposure to human inhalation exposure using ECHA Ch R8, Fig. 8.3. Human NOAEC = Oral NOAEL X 1/1.15 m³/kg/d X 0.5 absn. = 52.17 mg/m³

AF for dose response relationship:
1
Justification:
The NOAEC is reliable. No adjustment is required.
AF for differences in duration of exposure:
6
Justification:
The key studies were subacute toxicity studies in animals which require extrapolation to a working lifetime in humans using ECHA Ch R8, Table R. 8-5.
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling factor of 4 is not necessary because conversion is from rat oral to human inhalation (Ch R8. p.30)
AF for other interspecies differences:
1
Justification:
Remaining differences factor of 2.5 (Ch R8 p.29/30) is not required to rapid metabolism of the parent ester to the alcohol and MAA so no TD differences between rats and humans are expected.
AF for intraspecies differences:
10
Justification:
A combined interspecies and intraspecies assessment factor of 5 is using ECHA Ch R8, Characterisation of dose [concentration]-response for human health - Intraspecies differences, page 36.
AF for the quality of the whole database:
1
Justification:
The key studies were of high quality. No adjustment is required.
AF for remaining uncertainties:
1
Justification:
The duration factor of 6 is sufficient to address the limited sensitivity of the screening study.
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
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.5 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
240
Dose descriptor starting point:
NOAEL
Value:
120 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
120 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Starting point: NOAEL for reproductive and developmental toxicity in female rats given THFMA by oral gavage in an OECD 422 protocol.

Modification of starting point involves conversion of rat oral exposure to human dermal exposure using ECHA Ch R8, Ex. B5, page 69. Human NOAEC = Oral NOAEL X 1 (Absorption factor for oral to dermal route =1; ECHA Ch R8. page 25.)

AF for dose response relationship:
1
Justification:
The NOAEC is reliable. No adjustment is required.
AF for differences in duration of exposure:
6
Justification:
The key studies were subacute toxicity studies in animals which require extrapolation to a working lifetime in humans using ECHA Ch R8, Table R. 8-5.
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling factor of 4 is necessary due to conversion from rat oral to human dermal exposure (Ch R8. p.30)
AF for other interspecies differences:
1
Justification:
Remaining differences factor of 2.5 (Ch R8 p.29/30) is not required to rapid metabolism of the parent ester to the alcohol and MAA so no TD differences between rats and humans are expected.
AF for intraspecies differences:
10
Justification:
A combined interspecies and intraspecies assessment factor of 5 is using ECHA Ch R8, Characterisation of dose [concentration]-response for human health - Intraspecies differences, page 36.
AF for the quality of the whole database:
1
Justification:
The key studies were of high quality. No adjustment is required.
AF for remaining uncertainties:
1
Justification:
The duration factor of 6 is sufficient to address the limited sensitivity of the screening study.
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:
DNEL (Derived No Effect Level)
Value:
0.5 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
240
Dose descriptor starting point:
NOAEL
Value:
120 mg/kg bw/day
AF for dose response relationship:
1
Justification:
The NOAEL is reliable. No adjustment is required.
AF for differences in duration of exposure:
6
Justification:
The key studies were subacute toxicity studies in animals which require extrapolation to a working lifetime in humans using ECHA Ch R8, Table R. 8-5.
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling factor of 4 is necessary due to conversion from rat oral to human oral exposure (Ch R8. p.30)
AF for other interspecies differences:
1
Justification:
Remaining differences factor of 2.5 (Ch R8 p.29/30) is not required to rapid metabolism of the parent ester to the alcohol and MAA so no TD differences between rats and humans are expected.
AF for intraspecies differences:
10
Justification:
A combined interspecies and intraspecies assessment factor of 5 is using ECHA Ch R8, Characterisation of dose [concentration]-response for human health - Intraspecies differences, page 36.
AF for the quality of the whole database:
1
Justification:
The key studies were of high quality. No adjustment is required.
AF for remaining uncertainties:
1
Justification:
The duration factor of 6 is sufficient to address the limited sensitivity of the screening study
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