Registration Dossier

Administrative data

Endpoint:
dermal absorption, other
Remarks:
in silico prediction
Type of information:
calculation (if not (Q)SAR)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013
Reference Type:
publication
Title:
Handbook of Toxicology, Third Edition
Author:
Derelanko MJ, Auletta CS
Year:
2014
Bibliographic source:
CRC Press, Taylor and Francis Group, Handbook of Toxicolocy, General Toxocology, Body Wieght/Surface Area Conversion Tables 2.22 and 2.23, page 81

Materials and methods

Test guideline
Qualifier:
no guideline followed

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
SMILES structure: CC(=C)C(N)=O

Test animals

Species:
rat

Results and discussion

Percutaneous absorption
Remarks on result:
other: a moderate relative dermal absorption was calculated

Any other information on results incl. tables

Calculation of dermal absorption of methacrylamide in rats under the conditions of test guideline OECD 402, Acute dermal toxicity in rats:

Heylings at al have established an in silico model to predict dermal absorption of methacrylates and methacrylamides. This model is based onestablished model (Potts and Guy, 1992), using data derived with human epidermal membranes.

QSARs, when applied to estimating dermal permeability coefficients, are sometimes known as quantitative structure-permeability relationships (QSPeRs or QSPRs). Descriptors such as hydrophobicity, molecular size, and possibility of hydrogen bonding (which may describe non-covalent interactions with skin proteins) are important for the development of QSARs.

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 Kpis 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.

Potts RO and Guy RH (1992). Predicting Skin Permeability. Pharm. Res. 9(5): 663-669.

 

No.

Chemical Class

Test Chemical / Compound Identity

Acronym

Molecular Weight

Log P

Predicted Flux (μg/cm2/h)

Relative Dermal Absorption

33

Methacrylamides-tier 1

Methacrylamide

MAA

85.1

-0.15

42.625

Moderate

 

Parameters for prediction of dermal absorption in rats:

Surface of the body for application of test substance: not less than 10 % (OECD 402)

Exposure time: 24 hours (OECD 402)

Representative body weight rat: 0.15 kg (Handbook of Toxicology)

Representative surface area rat: 0.025 m² (Handbook of Toxicology)

 

Calculation:

10 % body surface of a rat correspond to 25 cm²

 

Absorption of methacrylamide in 1 rat under the conditions of OECD 402:

42.625 µg/cm²/h x 25 cm² x 24 h = 25.577 mg/150 g

25.277 mg/150 g correspond to 170.5 mg/kg

 

The maximum absorption of methacrylamide in rats under the conditions of OECD 402 is 170.5 mg/kg

 

Applicant's summary and conclusion

Conclusions:
The maximum dermal absorption of methacrylamide under the condtions of an acute dermal toxicity test acc. OECD 402 was calculated based on QSAR predictions by Heylings et al. An absorption of 170.5 mg/kg bw in maximum in rats was predicted.
Executive summary:

A predicted dermal flux of 42.625 µg/cm2/h was calculated, indicative for a moderate relative dermal absorption.