S-(3-(triethoxysilyl)propyl)octanethioate

Endpoint summary

Description of key information

The substance was found to be sensitising in a guinea pig maximisation test and a human volunteer repeated insult patch test. Ambiguous results were found in a Buehler study.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

02 Apr - 30 Jul 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

certified by the Federal Office of Public Health, 2000

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Study was completed in 2001 and was the standard skin sensitisation study at the time.

Species:

guinea pig

Strain:

other: Ibm: GOHI

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd, Biotechnology & Animal Breeding Division, Füllinsdorf, Switzerland
- Age at study initiation: 4 - 6 weeks
- Weight at study initiation: 316 - 396 g
- Housing: Individually in Makrolon type-4 cages with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz). Music was played during the light period.
- Diet: Pelleted standard Provimi Kliba 3418, batch nos. 33/00 and 90/01, guinea pig breeding / maintance diet, containing Vitamin C (Provimi Kliba AG, CH-4303 Kaiseraugst), ad libitum.
- Water: Community tap water from Füllinsdorf, ad libitum.
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30 - 70%
- Air changes (per hr): 10 - 15 air changes per hour
- Photoperiod (hrs dark / hrs light): Automatically controlled light cycle of 12 hours light and 12 hours dark.

Route:

intradermal and epicutaneous

Vehicle:

unchanged (no vehicle)

Concentration / amount:

100% (for all induction and challenge treatments)

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

100% (for all induction and challenge treatments)

No. of animals per dose:

10 animals for the test group and 5 animals for the control group

Details on study design:

RANGE FINDING TESTS:
The 100% concentration of the test item used for the intradermal application was well-tolerated systemically, causing mild skin irritation during the pretest. Epidermal application of the undiluted substance in the pretest did not cause any skin irritation.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3 pairs of intradermal injections (day 1) and 1 epidermal application (day 8) for 48 hours
- Test groups: TS and FCA
- Control group: Peanut oil and FCA
- Site: dorsal skin of the scapular region
- Duration: 48 hours for epidermal induction under occlusive dressing
- Concentrations: 100% for injections as well as for epidermal application

B. CHALLENGE EXPOSURE
- No. of exposures: single
- Day(s) of challenge: Day 22
- Exposure period: 24 hours under occlusive dressing
- Test groups: TS
- Control group: TS
- Site: 3 x 3 cm area of the left flank
- Concentrations: 100%
- Evaluation (hr after challenge): 24 and 48 hours after removal of the bandage

Positive control substance(s):

yes

Remarks:

2-Mercaptobenzothiazole

Positive control results:

A reliability check had been performed with 2-mercaptobenzothiazole half a year before in the same laboratory, confirming the sensitivity of the used animal strain.

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

100%

No. with + reactions:

0

Total no. in group:

5

Remarks on result:

no indication of skin sensitisation

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

100%

No. with + reactions:

0

Total no. in group:

5

Remarks on result:

no indication of skin sensitisation

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

100%

No. with + reactions:

8

Total no. in group:

10

Remarks on result:

positive indication of skin sensitisation

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

100%

No. with + reactions:

9

Total no. in group:

10

Remarks on result:

positive indication of skin sensitisation

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

1% in mineral oil

No. with + reactions:

10

Total no. in group:

10

Remarks on result:

positive indication of skin sensitisation

Reading:

2nd reading

Hours after challenge:

48

Group:

positive control

Dose level:

1% in mineral oil

No. with + reactions:

10

Total no. in group:

10

Remarks on result:

positive indication of skin sensitisation

Interpretation of results:

Category 1 (skin sensitising) based on GHS criteria

Conclusions:

Based on the findings in the adjuvant sensitization test (M&K-test) in guinea pigs and in accordance to Commission Directive 96/54/EEC, Y-15099 has to be classified and labelled as an extreme skin sensitizer.

Executive summary:

In order to assess the cutaneous allergenic potential of Y-15099, the Maximization-Test was performed in 15 (10 test and 5 control) female albino guinea pigs, in accordance with OECD Guideline No. 406 and the Directive 96/54/EEC, B.6.

The intradermal induction of sensitization in the test group was performed in the nuchal region with the undiluted test item (100%). The epidermal induction of sensitization was conducted for 48 hours under occlusive conditions with the undiluted test item one week after the intradermal induction and following pre-treatment of the test areas with 10% Sodium-Lauryl-Sulfate (SLS) 24 hours prior to application of the test item. The animals of the control group were treated with 10% SLS only.

Two weeks after epidermal induction the control and test animals were challenged by epidermal application of the undiluted test item under occlusive dressing.

Cutaneous reactions were evaluated at 24 and 48 hours after removal of the dressing.

No toxic symptoms were evident in the guinea pigs of the control or test group. No deaths occurred.

Eight (at the 24 -hour reading) and 9 (at the 48 -hour reading) out of 10 test animals showed discrete/patchy to moderate/confluent erythema after the challenge treatment with Y-15099 at 100%. No skin effect was observed in the control group.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

In order to assess the cutaneous allergenic potential of Y-15099, the Maximization-Test was performed in 15 (10 test and 5 control) female albino guinea pigs, in accordance with OECD Guideline No. 406 (Arcelin, 2001). The intradermal induction of sensitization in the test group was performed in the nuchal region with the undiluted liquid test item (100%). The epidermal induction of sensitization was conducted for 48 hours under occlusive conditions with the undiluted test item one week after the intradermal induction and following pre-treatment of the test areas with 10% Sodium-Lauryl-Sulfate (SLS) 24 hours prior to application of the test item. The animals of the control group were treated with 10% SLS only. Two weeks after epidermal induction the control and test animals were challenged by epidermal application of the undiluted test item under occlusive dressing. Cutaneous reactions were evaluated at 24 and 48 hours after removal of the dressing.

No toxic symptoms were evident in the guinea pigs of the control or test group. No deaths occurred. Eight (at the 24 -hour reading) and 9 (at the 48 -hour reading) out of 10 test animals showed discrete/patchy to moderate/confluent erythema after the challenge treatment with Y-15099 at 100%. No skin effect was observed in the control group. Thus, the test substance showed a skin sensitising potential under the conditions of this guinea pig maximisation test.

Y-15099 was evaluated as provided to determine its ability to sensitize the skin of normal volunteer subjects using a semi-occlusive standard repeated insult patch study procedure with nine 24 -hour induction applications and one 24 -hour challenge application (Dosik, 2002). Ninety-eight subjects completed the study.

One subject presented evidence of possible sensitization at challenge. Re-challenge was conducted under semi-occlusive conditions 2 weeks later. Reactions of erythema and oedema with papules were present. Two weeks after completing re-challenge, the subject participated in a Provocative Use phase. Product application was stopped by the subject after 6 applications due to "itching and redness". She was observed the following day and presented erythema and papules spreading beyond the open application area. Sensitization was confirmed with re-challenge and provocative use. Under the conditions employed in this study, there was evidence of sensitization to Y-15099.

The sensitization potential of Y-15099 was evaluated in a modified Buehler study according to OECD guideline 406 (Morris, 2001). Test groups of 10 male and 10 female Hartley albino guinea pigs were dosed topically with the undiluted test article weekly for a total of three induction exposures under occlusive conditions. The duration of each exposure was six hours. Two weeks after the last induction exposure, Test Group animals were challenge-dosed for detection of sensitization by topical application of the test article (10% concentration diluted in peanut oil) to previously unexposed areas of skin. The test article concentrations used for induction and challenge dosing were selected from range-finding results of the Primary Irritation Phase. A Naive Control Group of five male and five female guinea pigs was dosed a challenge in the same manner as the Test Group and served as irritation control. Reactions to challenge dosing were evaluated at approximately 24 and 48 hours after completion of exposure. Body weights and clinical observations were recorded a randomization (study day -1) and at study termination (study day 28). Positive control data were not generated as part of this study. The WIL Research Laboratories historical positive control data from a study conducted within six months of this test were used to demonstrate the reliability of the experimental design.

There were no deaths, test article-related clinical findings or remarkable body weigh changes in the main study. The number of animals with positive skin reactions upon challenge treatment was similar between treatment and control groups. Thus under the conditions of this study a clear interpretation of the results was judged to be difficult.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The test material concentration used for intradermal induction in the guinea pig maximisation test was 100% (>1%), which gave a sensitisation response of 90% (=30%).  This meets the criteria for Cat 1B. In addition the human data (IUCLID section 7.10) shows a very low (~1%) incidence of skin sensitisation, which supports that conclusion that the substance is not a strong or extreme sensitiser, and does not require classification in Cat 1A. According to CLP (1272/2008/EC) classification criteria for sensitisation, the substance is classified as skin sensitiser Category 1B, H317: May cause an allergic skin reaction.