Octyl methacrylate

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

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:

Octyl methacrylate

EC Number:

218-465-5

EC Name:

Octyl methacrylate

Cas Number:

2157-01-9

Molecular formula:

C12H22O2

IUPAC Name:

octyl 2-methylprop-2-enoate

Test material form:

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 n-OMA was evaluated through rat and human epidermis in an in vitro system.

Results and discussion

Signs and symptoms of toxicity:

not examined

Dermal irritation:

not examined

Absorption in different matrices:

Absorption of OMA through rat epidermis:
Octyl methacrylate readily absorbed through rat epidermis at a constant mean rate of 159 µg cm-2 hr-1. This rate of absorption was constant over the whole 24 hour exposure/sampling period. The total amount of chemical that was absorbed during the time of exposure was 4.2% of the donor reservoir.

Percutaneous absorption

Dose:

100 µl/cm²

Parameter:

percentage

Absorption:

4.2 %

Remarks on result:

other: 24 hours

Remarks:

Rat epidermis

Conversion factor human vs. animal skin:

Human epidermis appears to be several times less permeable to n-OMA 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 ±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.

Summary of the peak rates of absorption of MAA & alkyl-methacrylate esters through whole rat and human skin

Substance	Molecular volume	Rat whole rat				Human whole skin
		Peak rate of appearance (µg*cm-2*h-1)+- SEM		Period of peak absorption rate (hours)	% age of applied dose absorbed over x hours	Rate of absorption of ester/MAA (μg*cm-2 *hr-1)
		Ester	MAA
MAA	78.96		4584 ± 344	5-8	70%/24	327
MMA	93.1978	360± 20.9	108± 4.59	2.5-24	11.3%/24	33.4**
EMA	107.436		190**			13.6**
iBMA	135.646		56**			4**
nBMA	135.856		40± 9.4	2-10	0.4%/10	2.9**
6HMA	164.277		20**			1.4**
2EHMA	191.66		9**			0.6**
OMA	192.696		10.3 ± 0.65	8-24	0.24%/24	0.7**
12LMA	249.536		11.8 ± 2.11	8-24	0.26%/24	0.8**

The values in normal type were obtained experimentally, whilst those in italics are predicted values.

** Values are predicted rates of appearance of total chemical including parent ester and metabolite

Applicant's summary and conclusion

Conclusions:

Prediction due to the experimental results of analogue substances (n-BMA and 2-EHMA): OMA readily absorbs through rat and human epidermis. Human epidermis appears to be several times less permeable to OMA than rat epidermis.
Human epidermis appears to be 10 times less permeable to 2-EHMA than rat epidermis and 20 times less permeable to n-BMA than rat epidermis.

Executive summary:

The absorption of Octyl methacrylate (OMA) was evaluated through rat and human epidermis in an in vitro system. The technique measures the rate of absorption of OMA across the epidermis. Glass diffusion cells are employed to measure the amount of OMA that is received into a receptor chamber with respect to time, following the application of 100 µl/cm² of OMA to the epidermal surface. OMA absorbed at a constant rate throughoutr the period of exposure/sampling (0 -24 hours). The mean rate of absorption was calculated 159 µg cm-2 hr-1 and the total amount of chemical that was absorbed during the time of exposure was 4.2% (over 24 hours), respectively. OMA appears readily absorbed through rat and human epidermis, but human epideremisc is several times less permeable to OMA than rat epidermis. However, measuring the rate of absorption through rat and human epidermis provides a quantitative estimate for inter-species differences; however, because only the epidermal layer is used, no measure of metabolism during skin absorption is possible.