Ethylenebis(oxyethylene) bis[3-(5-tert-butyl-4-hydroxy-m-tolyl)propionate]

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From Jun. 20, 1990 to Aug. 5, 1991

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

No OECD guideline available with which to compare the study design. Details of the study methods, dose preparation, animal husbandry, observations and results are well described.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Ethylenebis(oxyethylene) bis[3-(5-tert-butyl-4-hydroxy-m-tolyl)propionate]

EC Number:

253-039-2

EC Name:

Ethylenebis(oxyethylene) bis[3-(5-tert-butyl-4-hydroxy-m-tolyl)propionate]

Cas Number:

36443-68-2

Molecular formula:

C34H50O8

IUPAC Name:

ethane-1,2-diylbis(oxyethane-2,1-diyl) bis[3-(3-tert-butyl-4-hydroxy-5-methylphenyl)propanoate]

Details on test material:

- Stability under test conditions: not applicable
- Storage condition of test material: at room temperature, radiolabelled substance at -20 degrees Celcius

Radiolabelling:

yes

Test animals

Species:

pig

Strain:

other: Troll Miniature

Sex:

male

Administration / exposure

Type of coverage:

occlusive

Vehicle:

other: Vaseline

Duration of exposure:

24 hours

Doses:

- Nominal doses: 2 or 20 mg/kg bw

No. of animals per group:

2/treatment group; 1 in control group

Control animals:

yes

Remarks:

vehicle only

Results and discussion

Percutaneous absorption

Dose:

2 or 20 mg/kg bw

Parameter:

percentage

Absorption:

ca. 0.5 %

Remarks on result:

other: 24 hour

Remarks:

reported to be 0.53%

Conversion factor human vs. animal skin:

Not reported

Any other information on results incl. tables

From the miniature pigs in animal group A (low dose administration) in the mean 0.17 % of the radioactivity administered were excreted during 168 h. From the animals of animal group B (high dose administration) 0.03 % of the total radioactivity administered were excreted during 168 h. The nominal amount weighed for radioactivity determination was 1 ml.

With faeces from Animal Al 0.01 % and from animal A2 less than 0.005 % of the radioactivity administered have been excreted. From Animals Bl and B2 the amount of test substance excreted was always below the limit of detection. Thus elimination of radioactivity with faeces was negligible. The nominal amount weighed of faeces samples for determination of radioactivity was 0.75 g. From animal group B (high dose) only the sample obtained 48 h pa from animal B2 was above the limit of detection. This sample contained 0.164 kBq and coresponded to 0.0005 % of the total administered radioactivity.

Applicant's summary and conclusion

Conclusions:

In the mean of all four animals the sum of the percentage of radioactivity, recovered in all biological samples, was below 0.5 % of the administered radioactivity. Because the % of test material in the residual carcass ofthe miniature pigs could not be determined, the percentage in carcass was approximated from a rat study. Therefrom in the mean 0.53 % of the total administered test item was totally absorbed by the animals via the dermal route.

Executive summary:

To investigate the absorption, distribution and elimination of dermally applied test material two animal groups of troll miniature pigs have been used. Animal group A received a low dose of about 19 mg test item and animal group B received a high dose of about 195 mg. The test substance was administered dermally for 24 hours. Urine and feces were collected from 0-168 h in 24 h intervals. With animal group A an average of 0.17 % of the administered radioactivity was eliminated in urine and less than 0.01 % in feces. With animal group B only 0.03 % was eliminated in urine and radioactivity in feces was always below the limit of detection. With both animal groups the major part of elimination of radioactivity in urine occurred during the first 48 h after administration of the test substance. Residues of the test item in organs and tissues were found in liver, kidney, adrenals, thyroid and

subcutaneous fat of the application area. The highest residues were found in liver (2-4 ng equiv./g with animal group A and 5-22 ng equiv./g with animal group B), subcutaneous fat of the application area (21-23 ng equiv./g with animal group A and 11 ng equiv./g with animal B2) and adrenals (1-3 ng equiv./g with animal group A and 16 ng equiv./g with animal Bl). The recovery of radioactivity in terms of radioactivity balances was 91 % for animal group A and 91.8 % for animal group B. Most of the radioactivity was recovered with the bandage, 90.2 % with animal group A and 91.6 % with animal group B. The blood and plasma level profiles showed with all animals only few samples above the limit of detection. Therefore a kinetic analysis of the blood and plasma level profiles could not be performed. The values were always below 2 ng equiv./g with animal group A and below 5 ng equiv./g with animal group B. In the mean of all four animals the sum of the percentage of radioactivity, recovered in all biological samples, was below 0.5 % of the administered radioactivity. Because the % of test material in the residual carcass ofthe miniature pigs could not be determined, the percentage in carcass was approximated from a rat study. Therefrom in the mean 0.53 % of the total administered test item was totally absorbed by the animals via the dermal route.