Registration Dossier

Administrative data

Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Test procedure in accordance with generally accepted scientific standards and described in sufficient detail. Read across was performed with butyl methacrylate.

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
Test material form:
other: liquid
Radiolabelling:
no

Test animals

Species:
rat
Strain:
Wistar
Sex:
male

Administration / exposure

Type of coverage:
open
Vehicle:
unchanged (no vehicle)
Duration of exposure:
48 hours
Doses:
100 µL/cm²
Details on in vitro test system (if applicable):
The absorption of nBMA was evaluated through rat and human epidermis and through rat whole skinin an in vitro system.

Results and discussion

Signs and symptoms of toxicity:
not examined
Dermal irritation:
not examined
Absorption in different matrices:
Absorption of nBMA through rat epidermis:
The fastest rate of absorption (mean) of nBMA through rat epidermis was measured to be 1543 µg cm-2 hr-1, which occurred between 0 and 6 hrs following the application of the chemical. The rate of absorption diminished from this time onwards, as indicated by a flattening of the curve. The total amount absorbed was calculated as 11% by 6 hours and 18.3% after 24 hours, at which point no more samples were taken.

Absorption of nBMA through human epidermis:
The rate of absorption of n-butyl methacrylate was linear over the duration of the experiment and was calculated to be 76.7 µg cm-2 hr-1. Just over 2% of the applied dose was absorbed over the exposure period.

Absorption of nBMA through whole (viable) rat skin
Only methacrylic acid (MAA) appeared in the receptor chambers of skin that had had n-butyl methacrylate applied to the surface. This would imply that all of the nBMA that is absorbed through the skin is hydrolysed by carboxylesterases that are present in this tissue. The peak rate of appearance of MAA, which occurred between 2 and 10 hrs, was calculated to be 40.9 µg cm-2 hr-1. There is a lag-time present between 0 and 2 hrs. This experiment did not extend beyond ten hours, and the percentage dose removed from the donor reservoir was 0.4%.
Percutaneous absorptionopen allclose all
Dose:
100 µL/cm²
Parameter:
percentage
Absorption:
18 %
Remarks on result:
other: 24 hours
Remarks:
Rat epidermis
Dose:
100 µL/cm²
Parameter:
percentage
Absorption:
2 %
Remarks on result:
other: 24 hours
Remarks:
Human epidermis
Dose:
100 µL/cm²
Parameter:
percentage
Absorption:
0.4 %
Remarks on result:
other: 10 hours
Remarks:
Whole (viable) rat skin
Conversion factor human vs. animal skin:
Human epidermis appears to be 20 times less permeable to nBMA than rat epidermis.

Any other information on results incl. tables

The results of the whole-skin penetration studies and the model predictions for 

other methacrylate esters are presented in the table.

Table: Summary of peak rates of absorption of MAA and alkyl-methacrylate
 

esters through whole rat skin.

 Ester     Ester      MAA     Period    %               Peak       Peak       Peak    Applied
                                         Absorp. Dose/
                                 (hours) length of exposure
-----------------------------------------------------------
MAA
                    4584    5 - 8       70%/24 hr  
MMA
        360         108     2.5 - 24    11.3%/24 hr
EMA
                    190**                              
i-BMA
                   56**                              
n-BMA
                   41     2 - 10      0.4%/10 hr
HMA
                     20**                              
2EHMA
                    9**                              
OMA
                     10     8 - 24      0.24%/24 hr
LMA
                     12     8 - 24      0.26%/24 hr
-----------------------------------------------------------

Ester Peak = rate of appearance of the parent ester (µg/cm2/hr)
 
MAA Peak = rate of appearance of the hydrolysis product, MAA (µg/cm2/hr)
Period Peak Absorp. = Time (hours) after application for peak absorption
% Applied Dose = total % absorbed
** Predicted rates of MAA from model estimates.

Applicant's summary and conclusion