Registration Dossier

Toxicological information

Dermal absorption

Currently viewing:

Administrative data

Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference
Reference Type:
other: Thesis
Title:
Unnamed
Year:
2002

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 428 (Skin Absorption: In Vitro Method)
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
- Name of test material (as cited in study report): Lauryl methacrylate
- Supplier: Röhm GmbH
Radiolabelling:
no

Test animals

Species:
rat
Strain:
Wistar
Sex:
male

Administration / exposure

Type of coverage:
open
Vehicle:
unchanged (no vehicle)
Duration of exposure:
48 hrs
Doses:
100 µl / cm²
Details on study design:
The absorption of Lauryl methacrylate was evaluated through rat epidermis and intact skin in an in vitro system. Values for human skin absorption
were extrapolated on the basis of a 14 times more efficient permeation through rat skin obtained in an epidermal PBPK model developed in this study.

Results and discussion

Signs and symptoms of toxicity:
not examined
Dermal irritation:
not examined
Absorption in different matrices:
Absorption of Lauryl methacrylate through rat epidermis:

The substance is readily absorbed through rat epidermis at a constant mean rate of 26.2 µg cm-2 hr-1.
This rate of absorption is virtually constant over the duration of the experiment.
The total amount of chemical that was absorbed during the time of exposure was 0.7 % of the applied dose.

Absorption of Lauryl methacrylate through whole rat skin:

Like the smaller esters investigated, Lauryl methacrylate was also metabolised to methacrylic acid as it was absorbed through whole rat skin. The peak rate of appearance of methacrylic acid was calculated to be 11.8 µg cm-2 hr-1, which occurred between 8 and 24 hours.
0.264 % of the Lauryl methacrylate was depleted from the donor reservoir over the 24 hr exposure period.
Percutaneous absorptionopen allclose all
Dose:
100 µl/cm²
Parameter:
percentage
Absorption:
0.7 %
Remarks on result:
other: 24 hrs
Remarks:
Rat epidermis
Parameter:
percentage
Absorption:
0.264 %
Remarks on result:
other: 24 hrs
Remarks:
whole rat skin
Conversion factor human vs. animal skin:
With respect to human skin, 14 times more efficient permeation through rat skin obtained in an epidermal PBPK model developed in this study.

Applicant's summary and conclusion

Conclusions:
Lauryl methacrylate is absorbed through rat skin to a low extent, 0.26 % within 24 hours.
The presence of carboxyl esterases in the skin completely hydrolyses the substance, only the resulting metabolite methacrylic acid was
demonstrated to pass through.
With respect to human skin, 14 times more efficient permeation through rat skin obtained in an epidermal PB-PK model developed in this study.
Executive summary:

The absorption of Lauryl methacrylate (LMA) was evaluated through whole rat skin and rat epidermis in an in vitro system.

The technique measures the rate of absorption of LMA across the rat skin and epidermis. Glass diffusion cells are employed to measure the amount of LMA that is received into a receptor chamber with respect to time, following the application of 100 µl/cm² of LMA to the epidermal surface. The mean rate of absorption was 26.2 µg cm-2 hr-1 for rat epidermis and 7.72 µg cm-2 hr-1 for whole rat skin.

The total amount of chemical that was absorbed during the time of exposure was 0.7 % (rat epidermis) and 0.26 % (rat whole skin) over 24 hours, respectively. LMA appears to be absorbed through rat skin and epidermis to a low extent As indicated by a PB-PK model used in this study, human skin is 14 times less permeable to LMA than rat skin.

NOTE: Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.