4,4,13,13-tetraethoxy-3,14-dioxa-8,9-dithia-4,13-disilahexadecane

Endpoint summary

Description of key information

In the key read-across sensitisation study conducted according to OECD Test Guideline 406 (guinea pig maximization test) and in compliance with GLP, the related substance bis[3-(triethoxysilyl)polysulfides (“polysulfides”; CAS No. 211519-85-6, EC No. 915-673-4) was not considered to be a skin sensitiser (WIL Research Laboratories, 2002). The study identified a sensitization index of 5% (less than the 30% or higher specified by ECHA for considering a substance sensitising).

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:

from 19 September 2000 to 21 October 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

An LLNA study was not performed because there is an existing reliable study for skin sensitisation using the Guinea Pig Maximisation test method. Furthermore, the LLNA test method is not considered to be suitable for substances that contain silicon. Please refer to the attached document for further details.

Species:

guinea pig

Strain:

other: Hartley [Crl:(HA)BR]

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Charles River Labs, Raleigh, NC, USA
- Age at study initiation: young adults
- Weight at study initiation: 291-339 g (males); 285-315 g (females)
- Housing: 1/suspended wire-mesh cage
- Diet: standard ad libitum
- Water: drinking water ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 67-73° F
- Humidity (%): 34-69
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

IN-LIFE DATES: From: 2000-09-19 To: 2000-10-21

Route:

intradermal and epicutaneous

Vehicle:

other: ethanol

Concentration / amount:

Intradermal induction: 0.1 mL of 5% test substance in ethanol; 5% in 1:1 FCA:saline
Topical induction: 0.4 mL of neat test substance (100%)

Day(s)/duration:

Day 0 for intradermal injection, Day 7 for topical application/48h of application for the closed patch

Adequacy of induction:

highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

other: ethanol

Concentration / amount:

Topical challenge: 0.3 mL of 25% test substance in ethanol

Day(s)/duration:

Day 22/24h of application

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

test: 10/sex
positive control: 5/sex
negative control: 5/sex

Details on study design:

RANGE FINDING TESTS:
primary irritation phase: intradermal (2/sex) 1, 3, 5% tested in mineral oil and 1:1 FCA:saline; topical (4/sex) 2.5, 5, 10, 25, 50% in ethanol and 100%

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal-3 paired injections, topical)
- Exposure period: topical 48h
- Test groups: 10/sex
- Control group: positive 5/sex; negative 5/sex
- Site: two rows of 3 sites, one row either side of dorsal mid-line
- Frequency of applications: intradermal treatment day 0; topical induction day 7
- Duration: induction period continues to day 21
- Concentrations:
intradermal: 1:1 FCA saline; 5% TS in ethanol; 5% TS in 1:1 FCA:saline
topical: 100% TS

B. CHALLENGE EXPOSURE
- No. of exposures: 1 (at two sites: TS and vehicle)
- Day(s) of challenge: day 22
- Exposure period: 24h
- Test groups: 10/sex
- Control group: positive 5/sex; negative 5/sex
- Site: flank
- Concentrations: 25% TS in ethanol
- Evaluation (hr after challenge): 24 and 48 h following patch removal

Challenge controls:

negative control: 25% TS in ethanol
positive control: 10% HCA (alpha-hexylcinnamaldeyde) in acetone

Positive control substance(s):

yes

Remarks:

alpha-hexylcinnamaldeyde

Positive control results:

See table 1.
Based on the incidence index of 100%, the positive control material (HCA) was judged to be a sensitizing agent under the conditions of this study.

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

25% TS

No. with + reactions:

1

Total no. in group:

20

Clinical observations:

Dermal scores of 1 were reported in the negative control group. Scores >1 in the test group were judged to indicate sensitization.

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

25% TS

No. with + reactions:

1

Total no. in group:

20

Clinical observations:

Dermal scores of 1 were reported in the negative control group. Scores >1 in the test group were judged to indicate sensitization.

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

ethanol

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

ethanol

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

10% solution of hexacinnamaldehyde

No. with + reactions:

10

Total no. in group:

10

Remarks on result:

positive indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

positive control

Dose level:

10% hexacinnamaldehyde

No. with + reactions:

10

Total no. in group:

10

Remarks on result:

positive indication of skin sensitisation

Table 1: Incidence of dermal response to challenge dosing

GROUP	MATERIAL	INTERVAL	DERMAL SCORES*				NO. ANIMALS	SENSITIZATION INCIDENCE INDEX**	SEVERITY INDEX***
			0	1	2	3
Test	TS	24h	3	16	1	0	20	1/20=5%	18/20=0.9
		48h	7	12	1	0	20		14/20=0.7
	vehicle	24h	20	0	0	0	20	0/20=0%	0
		48h	20	0	0	0	20		0
Positive control	HCA in vehicle	24h	0	7	3	0	10	10/10=100%	13/10=1.3
		48h	3	6	1	0	10		8/10=0.8
	vehicle	24h	10	0	0	0	10	0/10=0%	0
		48h	10	0	0	0	10		0
Negative control	TS	24h	5	5	0	0	10	n/a	5/10=0.5
		48h	9	1	0	0	10		1/10=0.1
	vehicle	24h	10	0	0	0	10	n/a	0
		48h	10	0	0	0	10		0

*Skin reactions were graded:

0 no reaction or very slight dispersed redness. No swelling.

1 slight patchy or confluent erythema

2 moderate and confluent erythema and/or slight swelling

3 severe erythema and/or moderate to severe swelling

** Sensitization incidence index: number of animals with dermal scores greater than those of the negative control group at 24h or 48h, divided by the number of animals tested. Grades of 1 or greater are considered indicative of sensitization in the positive control group

*** Severity index: the sum of test grades divided by the number of animals tested (given for 24h and 48h observations separately)

Interpretation of results:

GHS criteria not met

Conclusions:

In a guinea pig maximisation test study with adjuvant, conducted according to OECD Test Guideline 406 and in compliance with GLP, a sensitisation index of 5% for polysulfides was identified. EU criteria for sensitisation by skin contact would require a positive response in at least 30% of the test group. Therefore polysulfides is not considered to be a skin sensitiser.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

The key read-across study for skin sensitisation was conducted in accordance with the OECD Test Guideline 406 and in compliance with GLP. In this study, the test material polysulfides was administered to 20 guinea-pigs in a guinea pig maximisation test as an intradermal/epicutaneous induction exposure, followed by an occlusive, epicutaneous challenge dose, and appropriate negative and positive controls were in place. There were no deaths, clinical findings or remarkable body weight changes. A sensitization index of 5% was identified (compared to the ECHA criterion of 30% or higher), and the test material was concluded to be not sensitising to guinea pig skin. (WIL Research Laboratories, 2002).

The registered substance contains S2 as the main constituent, with S3 present as an impurity. The polysulfides substance in the read across study contained up to 25% of the registered substance. The other constituents were the structurally similar analogue substances S3 and S4. Due to the structural similarity and similar physicochemical properties, the read-across substance is considered to be representative of the registered substance. Since the polysulfides study gave a clear negative result, there is no reason to expect a positive result from a higher proportion of the S2 constituent. See discussion in the reproductive toxicity section endpoint summary (Section 7.8, section 5.9 for the CSR) for a more detailed justification for the read-across approach.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the available data, 4,4,13,13-tetraethoxy-3,14-dioxa-8,9-dithia-4,13-disilahexadecane does not require classification for sensitisation according to Regulation (EC) No. 1272/2008.