1-[difluoro(trifluoromethoxy)methoxy]-1,2,2-trifluoroethylene

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

80.4 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):

75

Dose descriptor starting point:

NOAEC

Value:

12 000 mg/m³

Modified dose descriptor starting point:

NOAEC

Value:

6 030 mg/m³

Explanation for the modification of the dose descriptor starting point:

The dose descriptor is modified according to the following :

Modified inhal. human NOAEC = rat inhal NOAEC * exp. cond. rat/expo. cond. human

Modified inhal. human NOAEC = 12000 mg/m3 * 6h/8h * 1 * 6.7 m3 (8h)/10 m3 (8h) = 6030 mg/m3

with modifications applied:

	Rat experimental	Worker exposure	correction
Point of departure	Inhalation NOAEC: 12000 mg/m3
exposure condition (hours)	6h/day	8h/day	0.75
exposure condition (days/week)	7 days/week (Default is 5d/week)	5 days/week	Default: 1
sRV (human)		6.7 m3/8h shift	6.7
wRV (human)		10 m3 /8h shift (light work)	10
			0.5025

AF for dose response relationship:

1

Justification:

Default (DNEL calculator)

AF for differences in duration of exposure:

6

Justification:

sub-acute study

AF for interspecies differences (allometric scaling):

1

Justification:

Default (DNEL calculator)

AF for other interspecies differences:

2.5

Justification:

Default (DNEL calculator)

AF for intraspecies differences:

5

Justification:

Default (DNEL calculator)

AF for the quality of the whole database:

1

Justification:

Default (DNEL calculator)

AF for remaining uncertainties:

1

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

40.27 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

75

Dose descriptor:

NOAEC

Value:

3 020 mg/m³

AF for dose response relationship:

1

Justification:

Default value. A dose-dependent response was observed.
The effects on the nasal epithelium were observed only at the highest dose.

AF for differences in duration of exposure:

6

Justification:

Default value. Local effects were observed in a repeated-dose toxicity study (28-day/OECD422), but not in the acute inhalation study following a single exposure.

AF for interspecies differences (allometric scaling):

1

Justification:

The starting point is an inhalation study

AF for other interspecies differences:

1

Justification:

Findings were alterations in the nasal cavity. A greater sensitivity in rats is usually observed compared to humans because of the physiological differences in the rat nasal cavity (in particular due to the larger epithelium surface in contact with incoming airflow).

AF for intraspecies differences:

5

Justification:

Default guidance value for workers

AF for the quality of the whole database:

1

Justification:

Default value. Effects on the nasal cavity were documented in a reliable 28-day study in rats.

AF for remaining uncertainties:

2.5

Justification:

No local effects were identified in the acute inhalation toxicity study.
Local effects on nasal ephitelium are probably related to the exposure duration as they were only observed in the repeated dose study by inhalation.
In the absence of information related to the mechanism leading to the nasal effects, an assessment factor for remaining uncertainty is applied.

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:

11.4 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):

300

Dose descriptor starting point:

NOAEC

Value:

12 000 mg/m³

Modified dose descriptor starting point:

NOAEL

Value:

3 420 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The dose descriptor is modified according to the following exposure conditions:

Modified inhal. human NOAEC = rat inhal NOAEC * exp. cond. rat/expo. cond. human

Modified inhal. human NOAEC = 12000 mg/m3 * 6h/8h = 9000 mg/m3

 

The dose descriptor is then corrected for absorption differences, if any.

Modified dermal human NOAEL = rat inhal NOAEC * sRVrat * ABS(inhal,rat)/ABS(dermal, rat) * ABS (dermal, rat)/ABS (dermal, human)

Modified inhal. human NOAEC = 9000 mg/m3 * 0.38 m3/kg/d * 1 = 3420 mg/kg/day

with Default inhalation absorption = 1 and Default dermal absorption = 1

and the following modifications

	Rat (experimental)	gen. pop. exposure	correction
Point of departure	Inhalation NOAEC: 12000 mg/m3
exposure condition (hours)	6h/day	8h/day	0.75
exposure condition (days/week)	7 days/week (Default is 5d/week)	7 days/week	Default applied 1
Absorption (inahalation)	1
Absorption (dermal)	1	1
sRV	0.38 m3/kg/d (6h --> 8h)

 

 

AF for dose response relationship:

1

Justification:

Default (DNEL calculator)

AF for differences in duration of exposure:

6

Justification:

Default (DNEL calculator)

AF for interspecies differences (allometric scaling):

4

Justification:

Default (DNEL calculator)

AF for other interspecies differences:

2.5

Justification:

Default (DNEL calculator)

AF for intraspecies differences:

5

Justification:

Default (DNEL calculator)

AF for the quality of the whole database:

1

Justification:

Default (DNEL calculator)

AF for remaining uncertainties:

1

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

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

20 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

Dose descriptor starting point:

NOAEC

Value:

12 000 mg/m³

Modified dose descriptor starting point:

NOAEC

Value:

3 000 mg/m³

Explanation for the modification of the dose descriptor starting point:

The dose descriptor is modified according to the following :

Modified inhal. human NOAEC = rat inhal NOAEC * exp. cond. rat/expo. cond. human

Modified inhal. human NOAEC = 12000 mg/m3 * 6h/24h = 3000 mg/m3

 

with the following modifications

	Rat experimental	gen. pop. exposure	correction
Point of departure	Inhalation NOAEC: 12000 mg/m3
exposure condition (hours)	6h/day	24h/day	0.25
exposure condition (days/week)	7 days/week (Default is 5d/week)	7 days/week	1
			0.25

 

 

AF for dose response relationship:

1

Justification:

Default (DNEL calculator)

AF for differences in duration of exposure:

6

Justification:

Default (DNEL calculator)

AF for interspecies differences (allometric scaling):

1

Justification:

Default (DNEL calculator)

AF for other interspecies differences:

2.5

Justification:

Default (DNEL calculator)

AF for intraspecies differences:

10

Justification:

Default (DNEL calculator)

AF for the quality of the whole database:

1

Justification:

Default (DNEL calculator)

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

20.13 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

150

Dose descriptor:

NOAEC

Value:

3 020 mg/m³

AF for dose response relationship:

1

Justification:

Default value. A concentration-dependent response was observed.
The effects on the nasal epithelium were observed only at the highest dose.

AF for differences in duration of exposure:

6

Justification:

Default value. Local effects were observed in a repeated-dose toxicity study (28-day/OECD422)

AF for interspecies differences (allometric scaling):

1

Justification:

The starting point is an inhalation study

AF for other interspecies differences:

1

Justification:

Findings were alterations in the nasal cavity. A greater sensitivity in rats is usually observed compared to humans because of the physiological differences in the rat nasal cavity (in particular due to the l
arger epithelium surface in contact with incoming airflow).

AF for intraspecies differences:

10

Justification:

Default guidance value for general population.

AF for the quality of the whole database:

1

Justification:

Default value. Effects on the nasal cavity were documented in a reliable 28-day study in rats.

AF for remaining uncertainties:

2.5

Justification:

No local effects were identified in the acute inhalation toxicity study.
Local effects on nasal ephitelium are probably related to the exposure duration as they were only observed in the repeated dose study by inhalation.
In the absence of information related to the mechanism leading to the nasal effects, an assessment factor for remaining uncertainty is applied.

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:

5.75 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):

600

Dose descriptor starting point:

NOAEC

Value:

12 000 mg/m³

Modified dose descriptor starting point:

NOAEL

Value:

3 450 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The dose descriptor is modified according to the following exposure conditions:

Modified inhal. human NOAEC = rat inhal NOAEC * exp. cond. rat/expo. cond. human

Modified inhal. human NOAEC = 12000 mg/m3 * 6h/24h = 3000 mg/m3

 

The dose descriptor is then corrected for absorption differences, if any.

Modified dermal human NOAEL = rat inhal NOAEC * sRVrat * ABS(inhal,rat)/ABS(dermal, rat) * ABS (dermal, rat)/ABS (dermal, human)

Modified inhal. human NOAEC = 3000 mg/m3 * 1.15 m3/kg/d * 1 = 3450 mg/kg/day

with Default inhalation absorption = 1 and Default dermal absorption = 1

and the following modifications

	Rat (experimental)	gen. pop. exposure	correction
Point of departure	Inhalation NOAEC: 12000 mg/m3
exposure condition (hours)	6h/day	24h/day	0.25
exposure condition (days/week)	7 days/week (Default is 5d/week)	7 days/week	1
Absorption (inahalation)	1
Absorption (dermal)	1	1
sRV	1.15 m3/kg/d (6h --> 24h)

 

AF for dose response relationship:

1

Justification:

Default (DNEL calculator)

AF for differences in duration of exposure:

6

Justification:

28 day study to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

inhalation to dermal

AF for other interspecies differences:

2.5

Justification:

Default (DNEL calculator)

AF for intraspecies differences:

10

Justification:

Default (DNEL calculator) for general population

AF for the quality of the whole database:

1

Justification:

Default (DNEL calculator)

AF for remaining uncertainties:

1

Justification:

Default (DNEL calculator)

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:

5.75 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):

600

Dose descriptor starting point:

NOAEC

Modified dose descriptor starting point:

NOAEL

Value:

3 450 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The dose descriptor is modified according to the following exposure conditions:

Modified inhal. human NOAEC = rat inhal NOAEC * exp. cond. rat/expo. cond. human

Modified inhal. human NOAEC = 12000 mg/m3 * 6h/24h = 3000 mg/m3

 

The dose descriptor is then corrected for absorption differences, if any.

Modified oral human NOAEL = rat inhal NOAEC * sRVrat * ABS(inhal,rat)/ABS(oral, rat) * ABS (oral, rat)/ABS (oral, human)

Modified oral human NOAEL = 3000 mg/m3 * 1.15 m3/kg/d * 1 = 3450 mg/kg/day

with Default inhalation absorption = 1 and Default oral absorption = 1

and the following modifications

	Rat (experimental)	gen. pop. exposure	correction
Point of departure	Inhalation NOAEC: 12000 mg/m3
exposure condition (hours)	6h/day	24h/day	0.25
exposure condition (days/week)	7 days/week (Default is 5d/week)	7 days/week	1
Absorption (inhalation)	1
Absorption (oral)	1	1
sRV	1.15 m3/kg/d (6h --> 24h)

 

AF for dose response relationship:

1

Justification:

Default (DNEL calculator)

AF for differences in duration of exposure:

6

Justification:

Default (DNEL calculator)

AF for interspecies differences (allometric scaling):

4

Justification:

Default (DNEL calculator)

AF for other interspecies differences:

2.5

Justification:

Default (DNEL calculator)

AF for intraspecies differences:

10

Justification:

Default for general population (DNEL calculator)

AF for the quality of the whole database:

1

Justification:

Default (DNEL calculator)

AF for remaining uncertainties:

1

Justification:

Default (DNEL calculator)

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

No direct exposure of the general population is anticipated as MOVE 3 is only used at industrial facilities.

The potential of exposure of general population is limited to indirect exposure by the environment, which is however limited because of the design of the industrial processes.