Isobutyl 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:

Isobutyl methacrylate

EC Number:

202-613-0

EC Name:

Isobutyl methacrylate

Cas Number:

97-86-9

Molecular formula:

C8H14O2

IUPAC Name:

isobutyl methacrylate

Details on test material:

Methacrylic acid from Ineos Acrylics (Lot 98/42; purity > 99%), methyl methacrylate from Ineos Acrylics (Lot 98/15; purity > 99%), ethyl methacrylat from Atofina (Lot 011666; purity: > 99%), i-butyl methacrylate from Ineos Acrylics (Lot 98/15; purity 99%), n-butyl methacrylate from Ineos Acrylics (Lot 98/15; purity 99%), hexyl methacrylate from Röhm GmbH (Lot 78070243; purity > 98%), 2-ethylhexyl methacrylate from Röhm GmbH (Lot 78080370; purity > 98%), octyl methacrylate from Röhm GmbH (Lot 22-902-13914-28; purity > 98%)

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 iBMA was evaluated through rat and human epidermis and through rat whole skin in an in vitro system.

Results and discussion

Signs and symptoms of toxicity:

not examined

Dermal irritation:

not examined

Absorption in different matrices:

The properties of i-BMA were determined by statistical analysis (single exponential fit). The original data were obtained with other members of the lower alkyl methacrylate category (MAA, MMA, n-BMA, 2-EHMA and n-octyl methacrylate).

Absorption of i-BMA through rat epidermis:
The fastest rate of absorption (mean) of nBMA through rat epidermis was estimated to be 1418 µg cm-2 hr-1.

Absorption of i-BMA through human epidermis:
The rate of absorption of isobutyl methacrylate was estimated to be 80 µg cm-2 hr-1. For n-BMA, the closest analogue measured, just over 2% of the applied dose was absorbed over the exposure period.

Absorption of i-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. The same would be expected for i-BMA because of the close structural analogy. This would imply that all of the i-BMA that is absorbed through the skin is hydrolysed by carboxylesterases that are present in this tissue. The peak rate of appearance of MAA was estimated to be 56 µg cm-2 hr-1. For n-BMA the 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:

ca. 18 %

Remarks on result:

other: 24 hours

Remarks:

Rat epidermis, measured with n-BMA

Percutaneous absorption 2

Dose:

100 µl/cm²

Parameter:

percentage

Absorption:

2 %

Remarks on result:

other: 24 hours

Remarks:

Human epidermis, measured with n-BMA

Percutaneous absorption 3

Dose:

100 µl/cm²

Parameter:

percentage

Absorption:

0.4 %

Remarks on result:

other: 10 hours

Remarks:

Whole (viable) rat skin, measured with n-BMA

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.

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:

i-BMA readily absorbs through rat and human epidermis and through whole rat skin. Human epidermis appears to be approx. 20 times less permeable to i-BMA than rat epidermis.

Executive summary:

The properties of i-BMA were determined by statistical analysis (single exponential fit). The original data were obtained with other members of the lower alkyl methacrylate category (MAA, MMA, n-BMA, 2-EHMA and n-octyl methacrylate).

The absorption of i-BMA was estimated for rat and human epidermis and through whole (viable) rat skin in an in vitro system. Glass diffusion cells were employed to measure the amount of substance that is received into a receptor chamber with respect to time, following the application of 100 µl/cm² of the respective substance to the epidermal surface. The calculated mean rate of absorption was 1418, 80 and 56 (appearance of MAA) µg cm-2 hr-1 and the total amount of chemical that was absorbed during the time of exposure was 18 (for the closest analogue n-BMA over 24 hours), 2 (n-BMA over 24 hours) and 0.4% (n-BMA over 10 hours), respectively. I-BMA appears to be readily absorbed through rat and human epidermis, but human epideremis is 20 times less permeable to i-BMA than rat epidermis.