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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
200.196 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
Value:
9 960 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
5 004.9 mg/m³
Explanation for the modification of the dose descriptor starting point:

The selected dose descriptor chose for the DNEL derivation is the NOAEC from a Klimisch 1 study (OECD 413, GLP), 90 days inhalation study on rats.

The DNEL for systemic effects via the inhalation route is deri ved on the NOAEC from the inhalation 90-day study in which the NOAEC was 9960mg/m3. Correction for respiratory rate and volume (rat to human worker): (6.7m3/d/10m3/d). (calculation from the REACH guidance "Chapter R.8: Characterisation of dose [concentration]-response for human health", page 69, example A.2) Correction for differences between human and experimental exposure conditions (worker)=0.75 (by default in DNEL calculator, corresponds to the ratio 6h/d/8h/d - guidance p 30) Therefore the corrected NOAEC for repeated-dose systemic effects via the inhalation route is 9960mg/ m3*(6.7m3/10m3) *0.75 =5004.9mg/m3.

AF for dose response relationship:
1
Justification:
Default (NOAEL highest dose tested)
AF for differences in duration of exposure:
2
Justification:
Default (subchronic to chronic)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (Oral rat to inhaled human)
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
5
Justification:
Default
AF for the quality of the whole database:
1
Justification:
Default (GLP study, following guideline OECD 413 without restriction)
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
200.196 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term 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:
DNEL (Derived No Effect Level)
Value:
30.523 mg/kg bw/day
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
Dose descriptor starting point:
NOAEC
Value:
9 960 mg/m³
Modified dose descriptor starting point:
NOAEL
Value:
3 052.28 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The selected dose descriptor chose for the DNEL derivation is the NOAEC from a Klimisch 1 study (OECD 413, GLP), 90 days inhalation study on rats. One study is available for oral repeated toxicity but it is of very low quality (Klimish 4), with NOAEL = 26mg/kgbw/day (knowing that this is the highest dose tested and that no effects were observed). Therefore the most relevant toxicity descriptor is the NOAEC of 9960mg/m3. The DNEL for systemic effects via the dermal route is then derived on the NOAEC from the inhalation 90-day study in which the NOAEC was 9960 mg/m3. Corrected dermal NOAEL = inhalatory NOAEC x sRVrat x (ABSinh-rat/ABSoral-human) (calculation from the REACH guidance "Chapter R.8: Characterisation of dose [concentration]-response for human health", page 72, example B.4) ABS=absorption rate: ABSinh-rat= 100% (by default) ABSoral-human=93% (toxicokinetics data) sRV rat= standard respiratory volume. For a 8h exposure =0.38m3/kgbw

Corrected dermal NOAEL = 9960mg/m3 x 0.38m3/kgbw x (100/93)=4069.7mg/kgbw/day Correction for differences between human and experimental exposure conditions (worker)=0.75 (by default in DNEL calculator) Therefore the NOAEL rat for repeated-dose systemic effects via the dermal route is =4069.7 X 0.75 = 3052.28 mg/kgbw/day

AF for dose response relationship:
1
Justification:
Default (NOAEL highest dose tested)
AF for differences in duration of exposure:
2
Justification:
Default (subchronic to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (oral rat to dermal human)
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
5
Justification:
Default
AF for the quality of the whole database:
1
Justification:
Default (GLP study, following guideline OECD 413 without restriction)
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
30.523 mg/kg bw/day
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
DNEL extrapolated from long term DNEL

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:
medium hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

There are no consumer uses of methyltetrahydrofuran, therefore DNELs for the dermal and inhalation routes are not required. A DNEL for the oral route is calculated for the purposes of assessment of humans exposed via the environment

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:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

There are no consumer uses of methyltetrahydrofuran, therefore DNELs for the dermal and inhalation routes are not required. A DNEL for the oral route is calculated for the purposes of assessment of humans exposed via the environment

Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

There are no consumer uses of methyltetrahydrofuran, therefore DNELs for the dermal and inhalation routes are not required. A DNEL for the oral route is calculated for the purposes of assessment of humans exposed via the environment

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:
10.996 mg/kg bw/day
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):
200
Dose descriptor starting point:
NOAEL
Value:
2 199.28 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The selected dose descriptor chose for the DNEL derivation is the NOAEC from a Klimisch 1 study (OECD 413, GLP), 90 days inhalation study on rats. One study is available for oral repeated toxicity but it is of very low quality (Klimish 4), with NOAEL = 26mg/kgbw/day (knowing that this is the highest dose tested and that no effects were observed). Therefore the most relevant toxicity descriptor is the NOAEC of 9960mg/m3. The DNEL for systemic effects via the dermal route is then derived on the NOAEC from the inhalation 90-day study in which the NOAEC was 9960 mg/m3. Corrected dermal NOAEL = inhalatory NOAEC x sRVrat x (ABSinh-rat/ABSoral-human) (calculation from the REACH guidance "Chapter R.8: Characterisation of dose [concentration]-response for human health", page 72, example B.4) ABS=absorption rate: ABSinh-rat= 100% (by default) ABSoral-human=93% (toxicokinetics data) sRV rat= standard respiratory volume. For a 24h exposure (general population exposure) =1,15m3/kgbw Corrected dermal NOAEL = 9960mg/m3 x 1,15m3/kgbw x (100/93)=12316mg/kgbw/day Correction for differences between human and experimental exposure conditions: 0.178571 (by default in DNEL calculator) Therefore the NOAEL rat for repeated-dose systemic effects via the dermal route (general population) is = 12316 X 0.178571= 2199.28mg/kg bw/day

AF for dose response relationship:
1
Justification:
Default (NOAEL highest dose tested)
AF for differences in duration of exposure:
2
Justification:
Default (subchronic to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (oral rat to oral human)
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default
AF for the quality of the whole database:
1
Justification:
Default (GLP study, following guideline OECD 413 without restriction)
AF for remaining uncertainties:
1
Justification:
Default (no remaining uncertainties)
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10.996 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
DNEL extrapolated from long term DNEL
Explanation for the modification of the dose descriptor starting point:

Short-term high exposures are considered unlikely (no specific uses implying high short-term exposure), DNELs for long-term exposure are therefore adequate to protect against short-term exposures and no separate short-term DNELs are calculated.

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

There are no consumer uses of methyltetrahydrofuran, therefore DNELs for the dermal and inhalation routes are not required. A DNEL for the oral route is calculated for the purposes of assessment of humans exposed via the environment