Butyl methacrylate

Dermal absorption

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

Guideline:

OECD Guideline 428 (Skin Absorption: In Vitro Method)

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Butyl methacrylate

EC Number:

202-615-1

EC Name:

Butyl methacrylate

Cas Number:

97-88-1

Molecular formula:

C8H14O2

IUPAC Name:

butyl methacrylate

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 absorption

Percutaneous absorption 1

Dose:

100 µl/cm²

Parameter:

percentage

Absorption:

18 %

Remarks on result:

other: 24 hours

Remarks:

Rat epidermis

Percutaneous absorption 2

Dose:

100 µl/cm²

Parameter:

percentage

Absorption:

2 %

Remarks on result:

other: 24 hours

Remarks:

Human epidermis

Percutaneous absorption 3

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.