2,2-Difluoroethyl Acetate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.03 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:

51 mg/m³

Modified dose descriptor starting point:

other: Corrected NOAEC (after corrections to account for time scaling and differences in respiratory volumes)

Value:

25.63 mg/m³

Explanation for the modification of the dose descriptor starting point:

Two modifications needed to be applied to calculate the correct starting point. Firstly, time scaling was required in order to extrapolate from exposure conditions used for experimental animals (exposed 6h/d and 5 d/wk) to exposure conditions for workers (exposed 8h/d and 5 d/wk). Secondly, it was required to account for the differences in respiratory volumes between experimental animals (6.7 m³ at rest) and humans (10 m³ under light activity). Applying these two modifications to the critical dose descriptor (i.e. NOAEC = 51 mg/m³) gives a starting point of 25.63 mg/m³ (= 51 x [6/8] x [6.7/10]).

AF for dose response relationship:

1

Justification:

In accordance with ECHA Guidance R.8 (version 2.1, November 2012), an AF of 1 was applied for dose-response relationship because the critical dose descriptor is a NOAEC.

AF for differences in duration of exposure:

2

Justification:

In accordance with ECHA Guidance R.8 (version 2.1, November 2012), an AF of 2 was applied for differences in duration of exposure in order to extrapolate from sub-chronic (i.e. 90-day study) to chronic exposure.

AF for interspecies differences (allometric scaling):

1

Justification:

In accordance with ECHA Guidance R.8 (version 2.1, November 2012), allometric scaling should not be applied in cases where doses in experimental animal studies are expressed as concentrations (e.g., in mg/m3 in air, ppm in diet, or mg/l in the drinking water) as these are assumed to be already scaled according to the allometric principle, since ventilation rate and food intake directly depend on the basal metabolic rate. Here, the critical dose descriptor used as a basis for the DNEL derivation comes from a repeated dose toxicity study by inhalation and is expressed in ppm or mg/m3 in air. The AF for interspecies differences (allometric scaling) was thus set equal to 1.

AF for other interspecies differences:

2.5

Justification:

In accordance with ECHA Guidance R.8 (version 2.1, November 2012), an AF of 2.5 was applied to account for other interspecies (i.e. other than related to allometric scaling) differences, i.e. toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part).

AF for intraspecies differences:

5

Justification:

In accordance with ECHA Guidance R.8 (version 2.1, November 2012), as standard procedure, a default AF of 5 was applied for workers.

AF for the quality of the whole database:

1

Justification:

The information available in the total toxicological database meets the tonnage driven data REACH requirements. In addition, the available data, all obtained from experimental GLP-compliant studies performed according to internationally recognized guidelines, are reliable and consistent. In accordance with ECHA Guidance R.8 (version 2.1, November 2012), an AF of 1 was thus applied for the quality of the whole database.

AF for remaining uncertainties:

1

Justification:

No additional AF was applied. For instance, the considered systemic effects (i.e. body weight reduction, decrease in blood glucose, and increase in urine ketones) are not among the severe effects for which an additional assessment factor could be required (i.e. respiratory sensitization, teratogenicity/developmental effects, reproductive or threshold carcinogenic effects).

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:

13.56 mg/m³

Most sensitive endpoint:

irritation (respiratory tract)

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

25

Dose descriptor:

NOAEC

Value:

506 mg/m³

AF for dose response relationship:

1

Justification:

In accordance with ECHA Guidance R.8 (version 2.1, November 2012), an AF of 1 was applied for dose-response relationship because the critical dose descriptor is a NOAEC.

AF for differences in duration of exposure:

2

Justification:

In accordance with ECHA Guidance R.8 (version 2.1, November 2012) when dealing with local tissue damage in the respiratory tract resulting from exposure by inhalation, an AF of 2 was applied for differences in duration of exposure in order to extrapolate from sub-chronic (i.e. 90-day study) to chronic exposure.

AF for interspecies differences (allometric scaling):

1

Justification:

In accordance with ECHA Guidance R.8 (version 2.1, November 2012), allometric scaling should not be applied if the effects are not dependent on metabolic rate or systemic absorption, as it is the case of local effects like the one considered here (i.e. local effects on the olfactory epithelium). In the present case, the corresponding AF was thus set equal to 1.

AF for other interspecies differences:

2.5

Justification:

In accordance with ECHA Guidance R.8 (version 2.1, November 2012) and given that there could be significant quantitative differences in deposition, airflow patterns, clearance rates and protective mechanisms between humans and animals, it was assumed that humans could be more sensitive than animals to effects on the respiratory tract. As a consequence, an AF of 2.5 was applied to account for other interspecies (i.e. other than related to allometric scaling) differences.

AF for intraspecies differences:

5

Justification:

In accordance with ECHA Guidance R.8 (version 2.1, November 2012), as standard procedure, a default AF of 5 was applied for workers.

AF for the quality of the whole database:

1

Justification:

The information available in the total toxicological database meets the tonnage driven data REACH requirements. In addition, the available data, all obtained from experimental GLP-compliant studies performed according to internationally recognized guidelines, are reliable and consistent. In accordance with ECHA Guidance R.8 (version 2.1, November 2012), an AF of 1 was thus applied for the quality of the whole database.

AF for remaining uncertainties:

1

Justification:

No additional AF was applied. For instance, the considered effect (i.e. local effects on the olfactory epithelium) is not among the severe effects for which an additional assessment factor could be required (i.e. respiratory sensitization, teratogenicity/developmental effects, reproductive or threshold carcinogenic effects).

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

General Population - Hazard via inhalation 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

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

The general population includes consumers and humans exposed via the environment:

• There is no consumer uses for DFEA, implying that there is no need to assess exposure of consumers and thus no need to derive a DNEL for general population on this basis.


• There is no direct release of DFEA in the environment. In addition, ECHA Guidance R.16 (section R.16.1.3.2. page 25, version 3.0, February 2016) indicates that an assessment of indirect exposure of humans via the environment is generally only conducted if:
  
  
  
  • the tonnage >1000 t/y or
  
  
  • the tonnage >100 t/Y and the substance is classified
    
    
    
    • as STOT RE 1; or
    
    
    • as a carcinogen or mutagen (any category); or
    
    
    • as toxic to reproduction (categories 1A or 1B).
    
    
    
    
  
  
  
  

DFEA does not comply with the above criteria, implying that there is no need to assess exposure of man via the environment and thus no need to derive a DNEL for general population on this basis.

As a result, no DNEL for the general population was derived for DFEA.