Registration Dossier

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:
OECD Guideline 428 (Skin Absorption: In Vitro Method)
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
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.