2-ethylhexyl 10-ethyl-4,4-dimethyl-7-oxo-8-oxa-3,5-dithia-4-stannatetradecanoate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific standards, is well documented, and acceptable for assessment. Composition/purity of the test substance not reported.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1975

Report date:

1975

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Maurer et al, 1975

Deviations:

not specified

GLP compliance:

no

Type of study:

Maurer optimisation test

Justification for non-LLNA method:

The study was conducted prior to the LLNA becoming the preferred method.

Test material

Test material information

Constituent 1

Reference substance name:

2-ethylhexyl 10-ethyl-4,4-dimethyl-7-oxo-8-oxa-3,5-dithia-4-stannatetradecanoate

EC Number:

260-829-0

EC Name:

2-ethylhexyl 10-ethyl-4,4-dimethyl-7-oxo-8-oxa-3,5-dithia-4-stannatetradecanoate

Cas Number:

57583-35-4

Molecular formula:

C22H44O4S2Sn

IUPAC Name:

2-ethylhexyl 2-{[({2-[(2-ethylhexyl)oxy]-2-oxoethyl}sulfanyl)dimethylstannyl]sulfanyl}acetate

Constituent 2

Reference substance name:

8-Oxa-3,5-dithia-4-stannatetradecanoic acid, 10-ethyl-4,4-dimethyl-7-oxo-, 2-ethylhexyl ester

IUPAC Name:

8-Oxa-3,5-dithia-4-stannatetradecanoic acid, 10-ethyl-4,4-dimethyl-7-oxo-, 2-ethylhexyl ester

Details on test material:

- Name of test material (as cited in study report): TK 11692
- Physical state: liquid
- Lot/batch No.: TK 11692
- Stability under test conditions: stabe

In vivo test system

Test animals

Species:

guinea pig

Strain:

other: Pirbright white

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Ciba-Geigy
- Weight at study initiation: 400 to 450 g
- Housing: individually in Macrolon cages, type 3
- Diet (e.g. ad libitum): NAFAG, Gossau SG pellets; ad libitum
- Water (e.g. ad libitum): ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 1 deg C
- Humidity 55 +/- 5%
- Photoperiod (hrs dark / hrs light): 14 hours light / 10 hour dark

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal

Vehicle:

physiological saline

Induction 2

Concentration / amount:

0.1 mL

Challenge

Challenge 1

Route:

intradermal

Vehicle:

physiological saline

Challenge 2

Concentration / amount:

0.1 mL

No. of animals per dose:

20

Details on study design:

During the first week volumes of 0.1 mL of the test substance (0.1%) in saline without adjuvant were injected intradermally on Monday at two sites (flank and back), and on Wednesday and Friday at each one site on the back. Twenty-one hours after administration, the animals were chemically depilated with Butoquick and three hours later the skin reaction was assessed under artificial lighting. The two largest diameters of the erythematous reaction in vertical alignment were measured (mm) and the skin-fold thickness was determined with a skin-fold gauge (mm). The individual "reaction volume" (uL) was calculated from these values for each reaction from each animal.

During the second and third week of induction the substance was mixed with adjuvant (Bacto Adjuvant, complete Freund's Adjuvant) in a 1:1 ratio. A total of 6 sensitizing doses of 0.1 mL were injected intracutaneously into the skin of the neck on Monday, Wednesday and Friday. The reactions were not evaluated on these occasions. The test for skin sensitization was performed two weeks after the last sensitizing treatment with the adjuvant mixture. For the test 0.1 mL of the same substance formulation, as employed during the first testing week, was injected intradermally on the previously untreated flank. Twenty-four hours later the reaction site was evaluated in the same manner as during the first testing week.

A group of 20 guinea pigs treated in the same manner with the control vehicle alone served as negative and another group treated with Dinitrochlorobenzene as positive control.

For each animal the mean value plus one standard deviation was calculated for the reaction volumes of the 4 intracutaneous injections from the first testing week. Ten days after the intracutaneous challenge injection subirritant doses at the test compound were applied epicutaneously under occlusive dressing which were left in place for 24 hours.

Challenge controls:

Twenty guinea pigs were treated in the same way with the control vehicle alone served as the negative controls.

Positive control substance(s):

yes

Remarks:

dinitrochlorobenzene

Results and discussion

Positive control results:

Significant skin sensitization
Rate of positive reactors: 20/20 animals

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.1%

No. with + reactions:

9

Total no. in group:

20

Remarks on result:

positive indication of skin sensitisation

Results 2

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

0.1%

No. with + reactions:

20

Total no. in group:

20

Remarks on result:

positive indication of skin sensitisation

Any other information on results incl. tables

Fisher's exact test
A positive reaction was observed.  
Erythema scores (Draize scores), 24  hours after removal of dressing, by sex:
Males: 4/10 had a score of 1
Females: 7/10 had a score of 1

Applicant's summary and conclusion

Interpretation of results:

other: Classified Category 1A according to EU criteria.

Conclusions:

Significant differences between the test group and the vehicle-treated controls were found with the test substance. The compound has therefore a skin sensitizing (contact allergenic) potential in albino guinea pigs.

Executive summary:

The optimization test was used, an intracutaneous sensitization procedure, to determine the sensitization potential of the test substance. The test was performed on groups of 10 male and 10 female guinea pigs. Dinitrochlorobenazene was used as the positive control. Skin sensitization was defined to occur for the challenge reaction whenever the reaction volume exceeded the mean value plus one SD of the 4 pre-sensitization reponses. Under the experimental conditions employed, significant differences between the test group and the vehicle treated controls were found with the test substance. Dinitrochlorobenzene caused significant skin sensitization potential in albino guinea pigs.