2,2,2-trifluoroethyl methacrylate

Dermal absorption

Administrative data

Endpoint:

dermal absorption

Type of information:

(Q)SAR

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a (Q)SAR model, with limited documentation / justification, but validity of model and reliability of prediction considered adequate based on a generally acknowledged source

Justification for type of information:

2. MODEL (incl. version number)
Potts and Guy prediction model

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
The physicochemical parameters of MW, Log P and saturated aqueous solubility have been used. An output of predicted steady-state flux has been calculated.

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
QSPeRs are statistically-derived linear and non-linear relationships between the steady-state permeability of a compound, usually measured from water, and various physicochemical descriptors and/or structural properties of the molecule. Typically, the main input parameter is the octanol:water partition coefficient. The dermal absorption measurement that has been most commonly used in QSAR modelling is the permeability coefficient Kp, because it characterises the steady-state permeation rate of a chemical from a specific vehicle through a given membrane. Although Kp is not directly suitable for application in risk assessment, it can be used in conjunction
with measured (or estimated) solubility in the same vehicle (e.g. water) to predict a maximum flux through the skin. Also, it can be combined in mathematical models with partition coefficient values for the skin to estimate non-steady state or finite dose absorption (IPCS, 2006). The prediction model used in this investigation for a set of methacrylate chemicals is based on an established model (Potts and Guy, 1992), using data derived with human epidermal membranes.
Categorisation is based upon the dermal absorption database developed at the laboratory between 1992 and 2012.

5. APPLICABILITY DOMAIN
no data

6. ADEQUACY OF THE RESULT
In a risk assessment context, QSPeRs are often used to identify chemicals that need further testing to define their likely dermal absorption potential in man more accurately. For example, if a new chemical belongs to a class of compounds known to be toxic, a simple QSPeR assessment may identify whether the risk is likely to be greater or less than the standards that already have sound in vitro or in vivo toxicological assessments. This wouldn’t necessarily negate further testing, but it can be very useful to reduce the number of compounds that require the more costly and time-consuming studies to establish the systemic exposure following dermal application.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2012

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The physicochemical parameters of MW, Log P and saturated aqueous solubility have been used in the evaluation of 56 methacrylate compounds. An output of predicted steady-state flux was calculated using the principles defined in the Potts and Guy prediction model. (Potts RO and Guy RH (1992). Predicting Skin Permeability. Pharm. Res. 9(5): 663- 669)

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

2,2,2-trifluoroethyl methacrylate

EC Number:

206-525-3

EC Name:

2,2,2-trifluoroethyl methacrylate

Cas Number:

352-87-4

Molecular formula:

C6H7F3O2

IUPAC Name:

2,2,2-trifluoroethyl methacrylate

Details on test material:

- Name of test material (as cited in study report): 2,2,2-Trifluoroethyl methacrylate

Test animals

Details on test animals or test system and environmental conditions:

not applicable; in silico modelling

Administration / exposure

Type of coverage:

other: not applicable; in silico modelling

No. of animals per group:

not applicable; in silico modelling

Results and discussion

Absorption in different matrices:

predicted flux: 0.144 µg/cm²/h; the relative dermal absorption is low

Any other information on results incl. tables

Based on a molecular weight of 168.12 g/mol and a log Kow of 1.56, the predicted flux of TFMEA is 0.144 µg/cm²/h; the relative dermal absorption is low.

Applicant's summary and conclusion

Conclusions:

The dermal absorption of TFMEA is predicted to be low; the predicted flux is 0.144 µg/cm²/h.

Executive summary:

The dermal absorption (steady-state flux) of TFMEA has been estimated by calculation using the principles defined in the Potts and Guy prediction model.

Based on a molecular weight of 168.12 g/mol and a logKow of 1.56, the predicted flux of TFMEA is 0.144 µg/cm²/h; the relative dermal absorption is low.