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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: 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
Details on test material:
- Supplier: Ineos Acrylics
- Name of test material (as cited in study report): n-butyl methacrylate
- Physical state: liquid
- Analytical purity: 99%
- Purity test date: no data
- Lot/batch No.: Acrylics 98/15
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 n-BMA 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 n-BMA 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 n-BMA 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 n-BMA 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 n-BMA 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 the results for the peak rates of absorption of MAA & alkylmethacrylate esters through rat & human epidermis

 

 

Rat epidermis

Human epidermis

Ester

Peak rate of absorption (μg cm-2hr-1) ±SEM

Period of peak absorption rate (hours)

% age of applied dose absorbed over x hours

Peak rate of absorption (μg cm-2hr-1) ±SEM

Period of peak absorption rate (hours)

% age of applied dose absorbed over x hours

MAA

23825±2839

0.5-4

93% / 24h

812

-

-

MMA

5888±223

2-8

46% / 16h

453±44.5

4-24

10% / 24h

EMA

4421

-

-

253

-

-

i-BMA

1418

-

-

80

-

-

n-BMA

1540±69

0-6

18% / 24h

76.7±9.8

0-24

2% / 24h

HMA

147

-

-

25

-

-

2EHMA

234±4.8

0-30

7.8% / 30h

22.7.7±3.7

3-24

0.6% / 24h

OMA

159±15

0-24

-

7.8

-

-


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:
n-BMA readily absorbs through rat and human epidermis and through whole rat skin. Human epidermis appears to be 20 times less permeable to 2-EHMA than rat epidermis.
Executive summary:

The absorption of n-BMA was evaluated through rat and human epidermis and through whole (viable) rat skin in an in vitro system. Glass diffusion cells are employed to measure the amount of n-BMA that is received into a receptor chamber with respect to time, following the application of 100 µl/cm² of n-BMA to the epidermal surface. The mean rate of absorption was 1540, 76.7 and 40.9 (appearance of MAA) µg cm-2 hr-1 and the total amount of chemical that was absorbed during the time of exposure was 18 (over 24 hours), 2 (over 24 hours) and 0.4% (over 10 hours), respectively. n-BMA appears readily absorbed through rat and human epidermis, but human epideremis is 20 times less permeable to n-BMA than rat epidermis.