Triisooctyl 2,2',2''-[(octylstannylidyne)tris(thio)]triacetate

Endpoint summary

Description of key information

Skin Irritation in vivo: Read-across to structurally similar substance (mixture MOTE: DOTE. 70:30) (CAS No 27107-89-7 and CAS 15571-58-1)

Under the conditions of this study the test material was not irritating to rabbits.

Eye Irritation in vivo: Read-across to structurally similar substance: Octyltin tris(2-ethylhexylmercaptoacetate) (MOTE) (CAS No 27107 -89 -7)

Under the conditions of this study the test material is not irritating to the eyes of rabbits.

Eye Irritation in vitro: Read-across to structurally similar substance: Octyltin tris(2-ethylhexylmercaptoacetate) (MOTE) (CAS No 27107 -89 -7)

Under the conditions of this study the test material was not irritating to the eye.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1st September 1992 to 11th September 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Reason / purpose for cross-reference:

other: read-across target

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: NDA
- Weight at study initiation: 2350 - 2670 g
- Housing: individually in metal cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum of 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 ºC
- Humidity (%): 30 - 70 %
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark


IN-LIFE DATES: From: 1st September 1992 To: 11th September 1992

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: control patch on left side of the animal.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): N/A


VEHICLE
- N/A

Duration of treatment / exposure:

4 hours

Observation period:

10 days.
Skin observations recorded at 1, 24, 48 and 72 hours according to the OECD scoring system.

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 12 - 16 cm²
- % coverage: NDA
- Type of wrap if used: gauze patch covered with aluminium foil


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not performed
- Time after start of exposure: N/A


SCORING SYSTEM: OECD 404 scoring system

Irritation parameter:

erythema score

Basis:

mean

Remarks:

3 rabbits

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: All three animals are a erythema score mean of 2

Irritation parameter:

edema score

Basis:

mean

Remarks:

3 rabbits

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: All three animals are a edema score mean of 1

Irritant / corrosive response data:

Because reactions were observed within 7 days after removing the bandages, the observation period was extended to 10 days to determine the reversibility of the skin reactions. Scaling was observed in all animals on day 7. The skin reactions observed were reversible until the end of the observation period on day 10.

Other effects:

None

Table 1. Individual skin reaction scores.

	Erythema			Edema
Animal number	738/F CF/TF	856/F CF/TF	720/F CT/TF	738/F CF/TF	856/F CF/TF	720/F CT/TF
After 1 hours	0/2	0/2	0/2	0/1	0/1	0/2
After 24 hours	0/2	0/2	0/2	0/1	0/1	0/1
After 48 hours	0/2	0/2	0/2	0/1	0/1	0/1
After 72 hours	0/2	0/2	0/2	0/1	0/1	0/1
Mean 24-72 hours	0/2	0/2	0/2	0/1	0/1	0/1
After 7 days	0/1s	0/1s	0/1s	0/0	0/0	0/0
After 10 days	0/0	0/0	0/0	0/0	0/0	0/0

Table 2. Individual bodyweights.

Animal number	738/F	856/F	720/F
At start of test	2350	2670	2560
After 3 days	2360	2780	2500
After 7 days	2470	2900	2700
After 10 days (end)	2580	2990	2750

Interpretation of results:

other: Not classified in accordance with EU criteria

Conclusions:

Under the conditions of this study the test material was not irritating to rabbits.

Executive summary:

The test material was applied to the skin of female New Zealand White rabbits via an occlusive patch. The test was conducted according to the standardised guideline OECD 404 and performed to GLP. The patch was applied for 4 hours and the rabbits were then observed for 10 days.

Under the experimental conditions employed the test material induced erythema and oedema reactions when applied to the clipped albino rabbit skin. The reactions were reversible until the reading of 10 days after application.

Under the conditions of this study the test material was not irritating to rabbits.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted on read-across material

Justification for type of information:

Read Across to Octyltin tris(2-ethylhexylmercaptoacetate) (MOTE) (EC Number 248-227-6 and CAS No 27107-89-7) based on structural similarity and hydrolytical behaviour, see attached justification.

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

erythema score

Basis:

mean

Remarks:

3 rabbits

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: All three animals are a erythema score mean of 2

Irritation parameter:

edema score

Basis:

mean

Remarks:

3 rabbits

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: All three animals are a edema score mean of 1

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

27th November 2010 to December 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Reason / purpose for cross-reference:

other: read-across target

Qualifier:

according to guideline

Guideline:

other: OECD guideline no. 438: “Isolated Chicken Eye Test Method for Identifying Ocular Corrosives and Severe Irritants”, adopted on 7 September 2009.

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

other: Chicken

Strain:

not specified

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Heads of the animals were obtained from poultry slaughterhouse v.d. Bor, Amersfoortseweg 118, Nijkerkerveen, the Netherlands.
- Age at study initiation: in vitro study, eyes from 7 week old chicks were used.
- Weight at study initiation: 1.5 - 2.5 kg


ENVIRONMENTAL CONDITIONS
not applicable.

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 30 µL
- Concentration (if solution): N/A


VEHICLE
not applicable.

Duration of treatment / exposure:

10 seconds

Observation period (in vivo):

Approximately 30 minutes after treatment observations were recorded

Number of animals or in vitro replicates:

in vitro study:
1 negative control eye.
3 positive control eyes
3 test eyes

Details on study design:

EXPERIMENTAL DESIGN
Within 2 hours after kill, eyes were carefully dissected and placed in a superfusion apparatus using the following procedure: First the eye lids were carefully removed without damaging the cornea and a small drop of Fluorescein sodium BP 2.0 % w/v was applied to the corneal surface for a few seconds and subsequently rinsed off with isotonic saline at ambient temperature. Next, the head with the fluorescein treated cornea were examined with a slit lamp microscope to ensure that the cornea is not damaged. If undamaged, the eye was further dissected from the head without damaging the eye or cornea. Care was taken to remove the eye ball from the orbit without cutting off the optical nerve too short.

The enucleated eye was placed in a stainless steel clamp with the cornea positioned vertically and transferred to a chamber of the superfusion apparatus. The clamp holding the eye was positioned in such a way that the entire cornea was supplied with isotonic saline from a bent, stainless steel tube, at a rate of 0.10- 0.15 mL/min. The chambers of the superfusion apparatus as well as the saline were temperature controlled at approximately 32 ºC.
After placing in the superfusion apparatus, the eyes were examined again with the slit lamp microscope to ensure that they are not damaged. Corneal thickness was measured using the Depth Measuring Attachment No. I for the Haag Streit slit lamp microscope. Corneal thickness was expressed in instrument units. An accurate measurement was taken at the corneal apex of each eye.

Eyes with a corneal thickness deviating more than 10 % of the average corneal thickness of the eyes, eyes that show opacity (score higher than 0.5), or are unacceptably stained with fluorescein (score higher than 0.5) indicating the cornea to be permeable, or eyes that show any other signs of damage, were rejected as test eyes and replaced.

In accordance with the proposed OECD guideline no. 438, three test eyes, one negative control eye and three positive control eyes were selected for testing. Each eye provided its own baseline values for corneal swelling, corneal opacity and fluorescein retention. For that purpose, after an equilibration period of 45- 60 minutes, the corneal thickness of the eyes was measured again to determine the zero reference value for corneal swelling calculations.
At time t = 0 (i.e. immediately after the zero reference measurement), the following procedure was applied for each test eye: The clamp holding the test eye was placed on paper tissues outside the chamber with the cornea facing upwards. Next, the eyes (corneas) were treated with the study substances 30µL for 10 seconds, followed by rinsing in 20 mL saline. After rinsing, each eye in the holder was returned to its chamber.

The eyes were examined at 0, 30, 75, 120, 180 and 240 minutes after treatment, using the criteria and scoring system. Fluorescein retention was only scored at 30 minutes after treatment. All examinations were carried out with the slit lamp microscope.
After the final examination the test material treated eyes and the negative and positive control eyes were preserved in a neutral aqueous phosphate buffered 4 % solution of formaldehyde. The corneas were embedded in paraffin wax, sectioned at 5 µM and stained with PAS (Periodic Acid-Schiff). The microscopic slides were filed in the archives and kept available for histopathological examination if considered relevant. In the case of Octyltin tris(2-ethylhexylmercaptoacetate) (MOTE), histopathological examination was considered not relevant, because no significant corneal effects were observed.

CONTROLS
- Positive control: 5 % (w/w) aqueous dilution of benzalkonium chloride
- Negative control: Saline.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): rinsed with 20 mL of saline solution
- Time after start of exposure: 10 seconds


SCORING SYSTEM:
In the ICE test, the eyes were examined at several time intervals after treatment to determine ocular effects using the parameters of corneal thickness (swelling), corneal opacity and fluorescein retention. Defined scoring scales were used for each parameter to define the severity of effects into four categories (I-IV). Four classes of eye irritancy (not irritating; slightly irritating; moderately irritating; severely irritating) were identified in the ICE test by combination of the categories defined for each of the evaluation parameters using the Prediction Model described in the box below.
Regulatory classification of eye irritants was based on the standard in vivo Draize Eye test. Various international regulatory classification systems are in use. Some systems recognise four classes, viz. non irritant, mild irritant (Category 2B), irritant (Category 2A), and severe irritant (Category 1) such as in the Globally Harmonized System (UN/GHS). The new EC Regulation 1272/2008 on classification, labelling and packaging of substances and mixtures (CLP) entered into force on the 20 January 2009. CLP implements the Globally harmonised System (GHS). The EC/GHS-classification system (CLP) recognises three classes, i.e. non-classified/non-irritant (NC/NI), irritant (Category 2) and severe irritant (Category 1).
The criteria used in the EC/GHS-regulatory classification system to identify the different classes of eye irritants are listed in any other information.

In order to translate the eye irritancy scores from the ICE test to an EC/GHS-regulatory classification, it was necessary to reconcile four irritancy classes from the ICE study into three classes within the EC/GHS-regulatory classification scheme. This was achieved through application of the prediction model defined below, which was based on scientific judgement and which was supported by several years of experience with conduct of the ICE test in parallel to the in vivo OECD 405 test. As a result of the reconciliation of the four ICE classes of irritancy into the 3 classes of the EC/GHS-regulatory classification system, it is possible that materials defined as slightly irritant using the ICE test Prediction Model may be identified in the EC-regulatory classification system as not classified/non-irritant.

TOOL USED TO ASSESS SCORE: hand-slit lamp and fluorescein

Irritation parameter:

cornea opacity score

Run / experiment:

Mean, 240 minutes

Value:

0.5

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Irritation parameter:

other: Swelling

Run / experiment:

Mean, 30 minutes

Value:

2.33

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Irritation parameter:

cornea opacity score

Run / experiment:

Mean, 30 minutes

Value:

0.16

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Irritation parameter:

cornea opacity score

Run / experiment:

Mean, 75 minutes

Value:

0.5

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Irritation parameter:

fluorescein retention score

Run / experiment:

Mean, 30 minutes

Value:

0.5

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Table 2: Summary of Results

Treatment	Maximum mean score for:			Irritation categories^1	Irritation Index^2	Classification (General, GHS and EC/GHS)
	Swelling %	Opacity	Fluorescein retention
Test material	2	0.5	0.5	I;I;I	22	NI/NI/NI
Positive control	29^5	3.0	3.0	III;IV;IV	149	severe/I/I
Saline (negative control)^6	0	0.0	0.0	n.a.^7	n.a.	n.a.

1        I = no effect; II = slight effect; III = moderate effect; IV = severe effect.

2        Irritation Index = maximum mean corneal swelling + maximum mean opacity (x 20) + mean fluorescein score (x 20).

3        2B = mild irritant; 2A = irritant; 1 = serious eye damage. United Nations-Economic Commission for(UN/ECE) (2003). Globally Harmonised System of Classification and Labelling of Chemicals (GHS). UN,and, 2007 (http://www.unece.org/trans/danger/publi/ghs/ghs_rev02/02files_e.html)

4        Blistering of epithelium.

5        Individual values based on one eye.

6 n.a. = not applicable

EC/GHS‑CLASSIFICATION (CLP) OF EYE IRRITANTS; EXTRAPOLATION FROM IN VITRO RESULTS TO IN VIVO CLASSIFICATION.

 

Extrapolation from thein vitroirritancy results to the EC/GHS classification will be carried out using scientific judgement, re-dividing the original four irritancy classes to three. The combinations of the three categories that are allowed for each of the three classifications are mentioned in the scheme below.

 

Regulatory Classification Combinations of the three categories.

NC/NI = not classified/not irritating            3 x I

                                                                          2 x I, 1 x II

                                                                          2 x II, 1 x I³

 

EC/GHS Category 2⁴:                                    3 x II

Irritating to eyes                                             2 x II, 1 x III

                                                                          1 x I, 1 x II, 1 x III¹

                                                                          3 x III

                                                                          2 x III, 1 x II

                                                                          2 x III, 1 x I

                                                                          2 x I, 1 x IV¹

                                                                          2 x II, 1 x IV¹

                                                                          2 x III, 1 x IV²

                                                                          1 x II, 1 x III, 1 x IV¹

 

EC/GHS Category 1⁴:                                     3 x IV

Irreversible effects on the eye/                     2 x IV, 1 x III

serious damage to eyes                                 2 x IV, 1 x II¹

                                                                          2 x IV, 1 x I¹

                                                                          immediate corneal opacity score 3

                                                                          corneal opacity score 4

                                                                          severe loosening of epithelium

¹ Combinations of categories less likely to occur.

 ²The combination of 2 x III, and 1 x IV can be considered as a borderline case between irritating and severely irritating.

 ³The combination of 2 x II, and 1 x I can be considered as a borderline case between not irritating and Category 2.

 ⁴Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labelling and packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 1999/45/EC, and amending Regulation (EC) No 1907/2006.

 

Interpretation of results:

other: Not classified in accordance with EU criteria

Conclusions:

Under the conditions of this study the test material was not irritating to the eye.

Executive summary:

The test material was evaluated neat in the Isolated Chicken Eye (ICE) test, according to the standardised OECD guideline no. 438, under GLP conditions.

Chicken eyes were obtained from slaughter animals used for human consumption. The isolated chicken eyes were exposed to a single application of the test material for 10 seconds using an application volume of 30 µL. Benzalkonium chloride (BAC) 5 % was used as the positive control and physiological saline as the negative control. Three main parameters were measured to disclose possible adverse eye effects: corneal thickness (expressed as corneal swelling), corneal opacity and fluorescein retention of damaged epithelial cells.

The negative control eye showed no corneal effects. The positive control caused moderate swelling, severe opacity and severe fluorescein retention. The calculated Irritation Index for the positive control was 149. The test material caused very slight swelling, very slight opacity and very slight fluorescein retention. The calculated Irritation Index was 22.

Under the conditions of this study the test material was not irritating to the eye.

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Read-across to structurally similar substance.

Justification for type of information:

Read Across to Octyltin tris(2-ethylhexylmercaptoacetate) (MOTE) (EC Number 248-227-6 and CAS No 27107-89-7) based on structural similarity and hydrolytical behaviour, see attached justification.

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

cornea opacity score

Run / experiment:

Mean, 240 minutes

Value:

0.5

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Irritation parameter:

other: Swelling

Run / experiment:

Mean, 30 minutes

Value:

2.33

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Irritation parameter:

cornea opacity score

Run / experiment:

Mean, 30 minutes

Value:

0.16

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Irritation parameter:

cornea opacity score

Run / experiment:

Mean, 75 minutes

Value:

0.5

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Irritation parameter:

fluorescein retention score

Run / experiment:

Mean, 30 minutes

Value:

0.5

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Reference 3

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26th January 2010 to 29th January 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Reason / purpose for cross-reference:

other: read-across target

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: young
- Weight at study initiation: 2148, 1958 and 2179 g
- Housing: individually in cages, fitted with a perforated floor (Rack Multifloor pen system, 785x840x450 mm) with cage enrichment.
- Diet (e.g. ad libitum): Standard laboratory diet ad libitum.
- Water (e.g. ad libitum): Tap water (N.V. Vitens) ad libitum
- Acclimation period: 6 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3 ºC
- Humidity (%): 45 - 70 %
- Air changes (per hr): 10 air changes/hour
- Photoperiod: 12 hrs dark / 12 hrs light


IN-LIFE DATES: From: 20th January 2010 To: 29th January 2010

Vehicle:

unchanged (no vehicle)

Controls:

other: Untreated left eye served as a control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): N/A


VEHICLE
N/A

Duration of treatment / exposure:

Single dose. Eyes held shut for at least 1 second.

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not washed
- Time after start of exposure: N/A


SCORING SYSTEM: See any other information section.


TOOL USED TO ASSESS SCORE: NDA

Irritation parameter:

cornea opacity score

Remarks:

opacity

Basis:

mean

Remarks:

3 rabbits

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Remarks:

3 rabbits

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Remarks:

3 rabbits

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

Discharge

Basis:

mean

Remarks:

3 rabbits

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

3 rabbits

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

At 1, 24, 48 and 72 hr after treatment, no signs of irritation were observed in the rabbits.

Other effects:

None reported.

Table 1. Individual scores.

Time after exposure	Animal number	Corneal effects		Iris	Conjuctivae		Discharge
		Score	Area		Redness	Swelling
1	2	0	4	0	0	0	0
	4	0	4	0	0	0	0
	6	0	4	0	0	0	0
24	2	0	4	0	0	0	0
	4	0	4	0	0	0	0
	6	0	4	0	0	0	0
48	2	0	4	0	0	0	0
	4	0	4	0	0	0	0
	6	0	4	0	0	0	0
72	2	0	4	0	0	0	0
	4	0	4	0	0	0	0
	6	0	4	0	0	0	0

Interpretation of results:

other: Not classified in accordance with EU criteria

Conclusions:

Under the conditions of this study the test material is not irritating to the eyes of rabbits.

Executive summary:

The eyes of 3 young New Zealand White rabbits were assessed for irritation by application of the test material according to the standardised guideline OECD 405. The study was conducted to GLP standard.

0.1 mL of the test material was administered into one eye of three rabbits, the eye was held shut for at least a second and then observed for 72 hours.

At 1, 24, 48 and 72 hr after treatment, no signs of irritation were observed in the rabbits.

Under the conditions of this study the test material is not irritating to the eyes of rabbits.

Reference 4

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted on read-across material

Justification for type of information:

Read Across to Octyltin tris(2-ethylhexylmercaptoacetate) (MOTE) (EC Number 248-227-6 and CAS No 27107-89-7) based on structural similarity and hydrolytical behaviour, see attached justification.

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

3 rabbits

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Remarks:

3 rabbits

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

discharge

Basis:

mean

Remarks:

3 rabbits

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

3 rabbits

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation - Read-across to structurally similar substance (mixture MOTE: DOTE. 70:30) (CAS No 27107-89-7 and CAS 15571-58-1)

In vivo

The test material was applied to the skin of female New Zealand White rabbits via an occlusive patch. The test was conducted according to the standardised guideline OECD 404 and performed to GLP. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

The patch was applied for 4 hours and the rabbits were then observed for 10 days.

Under the experimental conditions employed the test material induced erythema and oedema reactions when applied to the clipped albino rabbit skin. The reactions were reversible until the reading of 10 days after application.

Under the conditions of this study the test material was not irritating to rabbits.

Eye Irritation - Read-across to structurally similar substance: Octyltin tris(2-ethylhexylmercaptoacetate) (MOTE) (CAS No 27107-89-7).

In vivo

The eyes of 3 young New Zealand White rabbits were assessed for irritation by application of the test material according to the standardised guideline OECD 405. The study was conducted to GLP standard. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

0.1 mL of the test material was administered into one eye of three rabbits, the eye was held shut for at least a second and then observed for 72 hours.

At 1, 24, 48 and 72 hr after treatment, no signs of irritation were observed in the rabbits.

Under the conditions of this study the test material is not irritating to the eyes of rabbits.

In vitro

The test material was evaluated neat in the Isolated Chicken Eye (ICE) test, according to the standardised OECD guideline no. 438, under GLP conditions. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

Chicken eyes were obtained from slaughter animals used for human consumption. The isolated chicken eyes were exposed to a single application of the test material for 10 seconds using an application volume of 30 µL. Benzalkonium chloride (BAC) 5 % was used as the positive control and physiological saline as the negative control. Three main parameters were measured to disclose possible adverse eye effects: corneal thickness (expressed as corneal swelling), corneal opacity and fluorescein retention of damaged epithelial cells.

The negative control eye showed no corneal effects. The positive control caused moderate swelling, severe opacity and severe fluorescein retention. The calculated Irritation Index for the positive control was 149. The test material caused very slight swelling, very slight opacity and very slight fluorescein retention. The calculated Irritation Index was 22.

Under the conditions of this study the test material was not irritating to the eye.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No 1272/2008, the substance does not require classification with respect to skin and eye corrosion or irritation.