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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
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

Objective of study:
absorption
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
A series of in vitro and PBPK models were used to determine and predict  the skin absorption and metabolism of a series of methacrylate monomers.  Initial studies were conducted using the rat epidermal membrane model.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Methacrylic acid from Ineos Acrylics (Lot 98/42; purity > 99%), methyl methacrylate from
Ineos Acrylics (Lot 98/15; purity > 99%), n-butyl methacrylate from Ineos Acrylics (Lot
98/15; purity 99%), octyl methacrylate from Röhm GmbH (Lot 22-902-13914-28; purity
> 98%), lauryl methacrylate from Röhm GmbH (Lot 780803361; mix C12 and C15)

Test animals

Species:
other: rat and human
Strain:
Fischer 344
Sex:
not specified

Administration / exposure

Details on study design:
The rat whole-skin studies were conducted by collecting skin samples from  the flanks of Fischer 344 rats and placing a prepared sample in a  diffusion cell chamber. The receptor fluid was physiological saline. A  sample (100 µl/cm2) of methacrylic acid (MAA), methyl  methacrylate (MMA),  n-butyl methacrylate (nBMA), octyl methacrylate (OMA) or lauryl  methacrylate (LMA) was applied to the skin sample for up to 48 hours. The  amount of parent ester and MAA were measured in the receptor fluid. MAA  was also tested in a sample of human skin.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Toxicokinetic parametersopen allclose all
Toxicokinetic parameters:
half-life 1st:
Toxicokinetic parameters:
half-life 2nd:
Toxicokinetic parameters:
half-life 3rd:

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    % Absorp. Dose/(hours)                             

Peak        Peak     Peak    Applied 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

Conclusions:
Due to the slower absorption, methacrylate esters of molecular weight equal to or greater than EMA (114 a.m.u) are metabolized during penetration of the skin and are not expected to enter the circulation as the parent ester.
Executive summary:

In a valid scientific study, due to the slower absorption, methacrylate esters of molecular weight equal to or greater than EMA (114 a.m.u) are metabolized during penetration of the skin and are not expected to enter the circulation as the parent ester.