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

Endpoint summary

Description of key information

The key skin irritation/corrosion study (ASTA Medica AG, 1996) conducted in accordance with OECD Test Guideline 404 with minor deviations and in compliance with GLP found the test material, 4,4,13,13 -tetraethoxy-3,14-dioxa-8,9-dithia-4,13-disilahexadecane (“S2”; CAS No. 56706-10-6, EC No. 260-350-7), to be slightly irritating to the skin of rabbits.

The key eye irritation/corrosion study (ASTA Medica AG, 1996), conducted in accordance with OECD Test guideline 405 and in compliance with GLP found the test material to be not irritating to the eyes of rabbits. In a supporting study (WIL, 2000) conducted in accordance with OECD test guideline 405 and in compliance with GLP, a low purity S2 substance containing a higher proportion of an S3 isomer was found to be not-irritating.  

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 6 Feb 1996 to 19 Feb 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

fully occlusive covering

GLP compliance:

yes

Species:

rabbit

Strain:

other: White Russian

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: ASTA Medica AG, GERMANY
- Age at study initiation: 18-53 months
- Weight at study initiation: 2.41-2.71 kg
- Housing: 1/cage
- Diet (e.g. ad libitum): standard diet, ad libitum
- Water (e.g. ad libitum): drinking water, ad libitum
- Acclimation period: at least 1 day


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.0-20.0
- Humidity (%): 48-78
- Photoperiod (hrs dark / hrs light): 12h/12 h

IN-LIFE DATES: From: 1996-02-06 To: 1996-02-19

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: control: adjacent area of skin

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Concentration (if solution): neat

Duration of treatment / exposure:

4 h

Observation period:

9 days (study period suggests 13 days)

Number of animals:

3 (males)

Details on study design:

TEST SITE
- Area of exposure: 6.25 cm2
- % coverage: not stated
- Type of wrap if used: occlusive: cellulose gauze/cellulose fibre coated with natural rubber/synthetic film glue

REMOVAL OF TEST SUBSTANCE
- Washing (if done): gentle washing "as far as possible"
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize, 1944; OECD 404

Irritation parameter:

primary dermal irritation index (PDII)

Remarks:

erythema, eschar and oedema

Basis:

mean

Remarks:

of 3 animals

Time point:

other: 1, 24, 48, 72 h

Score:

1.5

Max. score:

8

Reversibility:

fully reversible within: 9 days

Remarks on result:

other: EU criteria (24, 48, 72 h): no two animals with a mean score >=2.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 9 days

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within:

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 6 days

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 9 days

Remarks:

Initial edema reversed by 24 hours, edema observed days 4, 6 and 7

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

6 days

Remarks on result:

no indication of irritation

Other effects:

No systemic effects reported

Table 1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility	Erythema & Eschar	Edema
	Max. score: 4	Max. score: 4
60 min	1,0,1	0,0,0
24 h	1,1,2	1,0,1
48 h	1,1,2	0,0,1
72 h	1,1,2	0,0,1
4 days	2,1,2	1,0,11
6 days	2,0,0,	1,0,0,
7 days	1	1
9 days	0	0
Average 24h, 48h, 72h	1.3	0.4
Reversibility*)	c	c
Longest time (unit) for reversion	9 days	9 days

 *) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

 

Interpretation of results:

GHS criteria not met

Conclusions:

An otherwise reliable study, conducted in accordance with OECD 404 and GLP but using an occlusive dressing, found the test material to be slightly irritating (PII 1.5) based on readings at 1, 24, 48 and 72 h. This result would be judged to be not irritating according to EU criteria. It is possible that the use of a semi-occlusive dressing might reduce irritation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From19 Feb 1996 to 1 Mar 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

other: White Russian

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: ASTA Medica AG, GERMANY

- Age at study initiation: 24, 60 months (males); 20 months (female)

- Weight at study initiation: 2.41-2.55 kg (male); 2.76 kg (female)

- Housing: 1/cage

- Diet (e.g. ad libitum): standard diet, ad libitum

- Water (e.g. ad libitum): drinking water, ad libitum

- Acclimation period: at least 1 day


ENVIRONMENTAL CONDITIONS

- Temperature (°C): 19.0-20.0

- Humidity (%): 50-84

- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: Not stated

Vehicle:

unchanged (no vehicle)

Controls:

other: none required - other eye used as control

Amount / concentration applied:

TEST MATERIAL

- Amount(s) applied (volume or weight with unit) 0.1 ml

- Concentration (if solution): neat

Duration of treatment / exposure:

No washout (examinations: 1, 24, 48, 72 h)

Observation period (in vivo):

72 h

Number of animals or in vitro replicates:

3 (2 males, 1 female)

Details on study design:

REMOVAL OF TEST SUBSTANCE

- Washing (if done): no washing reported

SCORING SYSTEM: Draize 1944, 1994; OECD 404

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein: 'pencil light'

Irritation parameter:

overall irritation score

Remarks:

irritation index

Basis:

mean

Time point:

other: 1, 24, 48, 72 h

Score:

2

Max. score:

110

Reversibility:

fully reversible within: 48 h

Remarks on result:

other: Irritation index 2/110 was deemed in this study to indicate no irritation (Gilman et al. 1983).

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

The test material did not cause significant ocular lesions, in two or more animals, as indicated by any of the following:

corneal opacity =>2...<3

iris lesion =>1...=<1.5

conjunctival redness =>2.5

conjunctival oedema (chemosis) =>2

based, in each case, on mean values for each animal derived from readings at 24, 48 and 72 h.

(EU criteria).

There were no irridial or corneal effects.

Table 1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility	Cornea	Iris	Conjunctivae redness	Conjunctival chemosis	Conjunctivae discharge
	Max. score: 4	Max. score: 2	Max. score: 3	Max. score: 4	Max score 3
60 min	0,0,0	0,0,0	1,1,1	1,1,0	2,2,2
24 h	0,0,0	0,0,0	0,1,1	0,0,0	0,0,0
48 h	0,0,0	0,0,0	0,0,0	0,0,0	0,0,0
72 h	0,0,0	0,0,0	0,0,0	0,0,0	0,0,0
Average 24h, 48h, 72h	0	0	0.2	0	0
Area effected	0	-	-	-	-
Maximum average score (including area affected, max 110; 24, 48, 72 h)	0/80 [corneal opacity x area x 5]	0/10 [iris score x 5]	0.4/20 [(redness + chemosis + discharge) x 2]
Reversibility*)	n/a	n/a	c	c	c
Average time (unit) for reversion	-	-	48 h	24 h	24 h

 

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

Gilman, M. R., Jackson E. M., Cervernm, D. R., Moreno, M. T. (1983). Relationship between the primary dermal irritation index and ocular irritation. J. Toxicol-Cut & Ocular Toxicol; 2: 107-117.

Interpretation of results:

GHS criteria not met

Conclusions:

A reliable study conducted in accordance with the standard guideline and GLP found the test material to be not irritating to the eyes of rabbits.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The key study for skin irritation with S2, conducted in accordance with OECD test guideline 404 and in compliance with GLP used an occlusive dressing and found the test material to be slightly irritating (PII 1.5) based on readings at 1, 24, 48 and 72 h (ASTA Medica 1996). This result would be judged to be not irritating according to EU criteria. It is possible that the use of a semi-occlusive dressing might reduce irritation.

A supporting study was also available for skin irritation, conducted according to an OECD test guideline 404 and in compliance with GLP (WIL Research Labs, 2000). The low purity S2 test material was similar to the registered substance but contained a higher proportion of an S3 isomer. The test material was found to be not irritating to the skin of rabbits.

The key study for eye irritation with S2, conducted in accordance with the OECD test guideline 405 and in compliance with GLP, found the test material to be not irritating to the eyes of rabbits (ASTA Medica 1996).

A supporting study was also available for eye irritation, conducted according to an appropriate OECD test guideline 405 and in compliance with GLP (WIL Research Labs, 2000). The test material was similar to the registered substance but contained a higher proportion of an S3 isomer.

The substance in the read across studies with low purity S2 contained approximately 65% of the registered substance. The other constituents are the structurally similar S1 and S3. Due to their structural similarity and similar physicochemical properties, the read-across substances are considered to be representative of the registered substance. See discussion in the reproductive toxicity section endpoint summary (Section 7.8, CSR section 5.9) for a more detailed justification for read-across approach.

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 irritation according to Regulation (EC) No. 1272/2008.