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Description of key information

Read-across from Dioctyltin bis (2-ethylhexylmercaptoacetate) (DOTE) (CAS No. 15571-58-1)

Skin Irritation: Under the conditions of the studies performed the test material was not classified as irritating to the skin.

Eye Irritation: Under the conditions of the study the test material was concluded not to be an eye irritant.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
12 June 1996 to 23 June 1996
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 (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: 2615 - 3446 g
- Housing: individually
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: for a minimum of six days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3°c
- Humidity (%): 30 - 70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12-h light/dark period.
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
undiluted, 0.5 mL on a 6.5 cm² area (1 x 1 inch).
Duration of treatment / exposure:
4 hours
Observation period:
12 days
Number of animals:
Four males and two females
Details on study design:
On the day to dosing, the hair was removed from the backs and flanks of the rabbits using an Oster small animal clipper. Each 0.5 mL dose was applied to an area of skin approximately 6.5 cm² under a secured two-ply gauze patch that was overwrapped with a gauze binder and secured with Dermiform tape. Plaxtic restraint collars were applied and remained on the animals for the duration of the exposure period. Each animal received a single, four-hour, semi-occluded exposure to the test material. At the end of four hours, the collars and bandages were removed and the sites wiped with disposable paper towels moistened with deionised water. The application sites were observed for erythema, oedema and other dermal findings approximately 30-60 minutes and 24, 48 and 72 hours after patch removal and once daily through day 11 if irritation persisted. Skin reactions were evaluated according to the OECD scoring system.
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
2.1
Max. score:
4
Reversibility:
fully reversible within: 11 days
Remarks on result:
other: Mean individual scores : 3-2-2-2-1.67-2
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 6 days
Remarks on result:
other: Mean individual scores : 1-0-0.33-0-0.33-0.33
Irritant / corrosive response data:
Six and four rabbits had slight to moderate erythema and very slight oedema, respectively. Desquamation was noted for three animals. Oedema completely subsided by day 6 or earlier. There were no other dermal findings. All irritation was reversible and completely subsided by day 11 or earlier. Desquamation was noted for three animals.

Primary dermal irritation study in albino rabbits

Individual dermal scores

0.5 mL/site

 

 

 

Erythema

 

Oedema

Animal

Sex

Site

0.5-1h

24h

48h

72h

Site

0.5-1h

24h

48h

72h

20850

M

A

2

3

3

3

A

0

1

1

1

20856

M

A

1

2

2

2

A

0

0

0

0

20873

M

A

0

2

2

2

A

0

0

0

1

20877

M

A

1

2

2

2

A

0

0

0

0

20899

F

A

1

1

2

2

A

0

0

0

1

20914

F

A

2

2

2

2

A

0

0

0

1

 

 

Total

7

12

13

13

Total

0

1

1

4

 

 

 

 

 

 

 

 

 

 

 

 

h = hours; M = Male; F = Female

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 skin.
Executive summary:

The skin irritation potential of the test material was investigated in a study which was conducted in accordance with the stamdardised guideline OECD 404, under GLP conditions.

During the study, they test material was applied undiluted on a patch on shaved rabbit skin. The exposure period was 4 hours.

The test material induced slight to moderate erythema on all rabbits and very slight oedema on four animals. Three rabbits had desquamation. There were no other dermal findings. All irritation was reversible and completely subsided by day 11 or earlier.

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

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 from Dioctyltin bis (2-ethylhexylmercaptoacetate) (DOTE) (CAS No. 15571-58-1), see attached justification.
Reason / purpose for cross-reference:
read-across source
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
2.1
Max. score:
4
Reversibility:
fully reversible within: 11 days
Remarks on result:
other: Mean individual scores : 3-2-2-2-1.67-2
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 6 days
Remarks on result:
other: Mean individual scores : 1-0-0.33-0-0.33-0.33
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Not specified
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
- Source:no data
- Age at study initiation:no data
- Weight at study initiation:2380-2480 g.
- Housing:individually
- Diet (e.g. ad libitum): not precised, ad libitum
- Water (e.g. ad libitum): not precised, ad libitum
- Acclimation period:no data

ENVIRONMENTAL CONDITIONS
- Temperature:20 ± 3 *C
- Humidity: 30-70 %
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light):12-h light/dark photoperiod.
Type of coverage:
not specified
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent vehicle
Amount / concentration applied:
Undiluted, 0.5 mL on a 12-16 cm^2 area.
Patches treated with water prior to application.
Duration of treatment / exposure:
4 hours
Observation period:
10 days
Number of animals:
3
Details on study design:
Prior to exposure (~24 hours), a 36 cm^2 area on the both flanks of each animal was shaved. Each animal was exposed to 0.5 mL of the test material via a treated 12-16 cm^2 gauze patch applied to the right flank. An untreated (control) gauze patch was applied to the opposite flank. Patches were moistened with distilled water prior to application, loosely covered with aluminum foil (36 cm^2), and held in place with adhesive tape for 4 hours.
At the end of the exposure period, the gauze patches were removed and the skin reaction was observed at 1, 24, 48, and 72 hours post-removal. Animals also were observed daily for signs of clinical toxicity and/or mortality. Skin reactions were evaluated according to the OECD scoring system and the irritant/corrosive potency of the test substance was classified according to EC Directive 83/467/EEC at least observation up to 10 days.
Irritation parameter:
erythema score
Basis:
mean
Remarks:
3 rabbits
Time point:
24/48/72 h
Score:
1.78
Max. score:
4
Reversibility:
fully reversible within: 10 days
Remarks on result:
other: Mean individual scores : 2 - 2 - 1.33
Irritation parameter:
edema score
Basis:
mean
Remarks:
3 rabbits
Time point:
other: 24-48-72 hours
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Mean individual scores : 1.67 - 1 - 1.33
Irritant / corrosive response data:
Positive reactions were observed within 7 days post-removal. Therefore, the observation period was extended to 10 days, in order to assess reversibility. Slight scaling was observed on 2 animals on day 3 post-removal; by day 7 post-removal, all animals exhibited slight scaling. All skin reactions observed were fully reversible within 10 days post-removal. Under the experimental conditions, the test substance was classified as an irritant.
Interpretation of results:
other: EU Criteria not classified
Conclusions:
Based on the test results, DOTE was a moderately skin irritant but not classified according to the regulation EC no.1272/2008 and the EU Directive 67/548/EEC.
Executive summary:

An OECD Guideline 404 (Acute Dermal Irritation / Corrosion) test was carried out with a mixture of DOT(2 -EHMA) and MOT(2 -EHMA). The mixture was applied undiluted on a patch on shaved rabbit skin. Positive reactions were observed within 7 days post-removal.  Therefore, the observation period was extended to 10 days, in order to assess  reversibility.  All skin  reactions observed were fully reversible within 10 days post-removal. Under the experimental conditions, the test substance was irritant.

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 from Dioctyltin bis (2-ethylhexylmercaptoacetate) (DOTE) (CAS No. 15571-58-1), see attached justification.
Reason / purpose for cross-reference:
read-across source
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
1.78
Max. score:
4
Reversibility:
fully reversible within: 10 days
Remarks on result:
other: Mean individual scores : 2 - 2 - 1.33
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Mean individual scores : 1.67 - 1 - 1.33
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
30 May 1996 to 09 October 1996
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:
EPA OTS 798.4500 (Acute Eye Irritation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Sex: males and females
- Body weights: 2828 and 4148 g at initiation of dosing
- Housing: individual suspended mesh-bottom cages
- Diet: ad libitum
- Water: ad libitum
- Acclimitisation: minimum of six days


ENVIRONMENTAL CONDITIONS
Room temperature: 66.5 - 68.2 °F
Relative humidity: 49.0 - 69.9 %.
Photoperiod: 12 hours light/12 hours dark
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
undiluted amount applied: 0.1 mL
Duration of treatment / exposure:
96 hour(s)
Observation period (in vivo):
4 days.
Animals observed twice daily for mortality.

Both eyes of the rabbits were examined for occular abnormalities prior to initiation of dosing, including the use of sodium fluorescein and UV light for detection of corneal abnormalities. Both eyes were examined macroscopically for ocular irritation using a hand-held penlight in accordance with the method of Draize.
Number of animals or in vitro replicates:
3/sex
Details on study design:
Eyes were not rinsed; the test material was placed directly into the cupped lower conjunctival sac of the right eye.
Body weight recorded on day 0 and at termination.
Irritation parameter:
cornea opacity score
Remarks:
Opacity
Basis:
mean
Remarks:
6 rabbits
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Remarks:
area
Basis:
mean
Remarks:
6 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:
6 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:
6 animals
Time point:
24/48/72 h
Score:
0.5
Max. score:
3
Reversibility:
fully reversible within: 4 days
Remarks on result:
other: Mean individual scores : 0.67-0.67-0.33-1.33-0-0
Irritation parameter:
conjunctivae score
Remarks:
chemosis
Basis:
mean
Remarks:
6 rabbits
Time point:
24/48/72 h
Score:
0.22
Max. score:
4
Reversibility:
fully reversible within: 4 days
Remarks on result:
other: Mean individual scores : 0-0.33-0-1-0-0
Irritation parameter:
conjunctivae score
Remarks:
discharge
Basis:
mean
Remarks:
6 rabbits
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
other: All mean individual scores were 0
Irritant / corrosive response data:
None of the rabbits vocalised upon installation of the test material.
The left (control) eyes were free of evidence of ocular irritation and other findings for the duration of the study.
There were no test material related deaths, clinical findings, or body weight changes during the study period. The maximum average score for the test material was 8.0 at one hour post instillation. Positive conjunctival irritation was noted for 4/6 rabbits. All animals had minor conjunctival irritation. There were no iridal or corneal findings. All irritation was reversible and completely subsided by day 4.
Other effects:
One female (no. 21091) lost 390g (14%) of initial (day 0) bodyweight. This weight loss was not considered to be related to test material administration. There were no other remarkable changes or differences observed in body weights during the study period.

Table 1. Individual ocular irritation scores for conjuctiva.

 Animal/sex 1h  (R-C-D) 24h (R-C-D)  48h (R-C-D)  72h (R-C-D)  4d  (R-C-D)
1 m 2 -1 -1 1 -0 -0 1 -0 -0 0 -0 -0  
2 m 2 -1 -1  1 -1 -0  1 -0 -0  0 -0 -0   
3 m 1 -1 -1  1 -0 -0  0 -0 -0  0 -0 -0   
4 f  2 -1 -2  2 -1 -0  1 -1 -0  1 -1 -0  0 -0 -0 
5 f  1 -1 -2  0 -0 -0  0 -0 -0  0 -0 -0   
6 f  2 -1 -1  0 -0 -0  0 -0 -0  0 -0 -0   
          

R-redness

C-chemosis

D-discharge

m-male

f-female

Table 2. Individual body weights (g).

Animal number Sex Initation (day 0) Termination (interval)
21044 m 2841 2898 (day 3)
21049 m 3159 3286 (day 3)
21055 m 2876 3027 (day 3)
20638 f 4148 4120 (day 4)
21072 f 3088 3125 (day 3)
21091 f 2828 2438 (day 3)
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 preliminary ocular irritation potential of the test material was evaluated in accordance with the stamdardosed guidelines OECD 405 and EPA OTS 798.4500, under GLP conditions.

During the study, single 0.1 mL doses of the test material were instilled into the lower conjuctival sac of the right eye of 6 New Zealand White rabbits. The eyelids were held closed for approximately 1 second and released. Left eyes were manipulated in a similar manner as the right eyes and served as contralateral controls. The eyes of all animals remained unwashed.

The eyes were examined for ocular reactions in accordance with the method of Draize at approximately 1, 24, 48, and 72 hours after dosing and on day 4 if irritation persisted. Sodium fluorescein was used to aid in revealing possible corneal damage at 24, 48, and 72 hours and on day 4. Postive conjunctival reactions were noted in the treated eye of 4 animals while minor conjuctival irritation was noted for all rabbits. There were no corneal or iridal findings. All irritation was reversible and completely subsided by day 4 or earlier.

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

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 from Dioctyltin bis (2-ethylhexylmercaptoacetate) (DOTE) (CAS No. 15571-58-1), see attached justification.
Reason / purpose for cross-reference:
read-across source
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Remarks:
area
Basis:
mean
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
Time point:
24/48/72 h
Score:
0.5
Max. score:
3
Reversibility:
fully reversible within: 4 days
Remarks on result:
other: Mean individual scores : 0.67-0.67-0.33-1.33-0-0
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0.22
Max. score:
4
Reversibility:
fully reversible within: 4 days
Remarks on result:
other: Mean individual scores : 0-0.33-0-1-0-0
Irritation parameter:
conjunctivae score
Remarks:
discharge
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
other: All mean individual scores were 0
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Read-across from Dioctyltin bis (2-ethylhexylmercaptoacetate) (DOTE) (CAS No. 15571-58-1)

Skin Irritation:

The skin irritation potential of the test material was investigated in a study which was conducted in accordance with the stamdardised guideline OECD 404, under GLP conditions. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

During the study, they test material was applied undiluted on a patch on shaved rabbit skin. The exposure period was 4 hours.

The test material induced slight to moderate erythema on all rabbits and very slight oedema on four animals. Three rabbits had desquamation. There were no other dermal findings. All irritation was reversible and completely subsided by day 11 or earlier.

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

Read-across data (mixture DOTE: MOTE. 75:25) (CAS No 15571-58-1 and CAS 27107-89-7)

An OECD Guideline 404 (Acute Dermal Irritation / Corrosion) test was carried out with amixture of DOT(2 -EHMA) and MOT(2 -EHMA). The mixture was applied undiluted on a patch on shaved rabbit skin. Positive reactions were observed within 7 days post-removal. Therefore, the observation period was extended to 10 days, in order to assess reversibility. All skin reactions observed were fully reversible within 10 days post-removal. Under the experimental conditions, the test substance was an irritant but was not requiring classification.

Read-across from Dioctyltin bis (2-ethylhexylmercaptoacetate) (DOTE) (CAS No. 15571-58-1)

Eye Irritation:

The ocular irritation potential of the test material was evaluated in accordance with the stamdardosed guidelines OECD 405 and EPA OTS 798.4500, under GLP conditions. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

During the study, single 0.1 mL doses of the test material were instilled into the lower conjuctival sac of the right eye of 6 New Zealand White rabbits. The eyelids were held closed for approximately 1 second and released. Left eyes were manipulated in a similar manner as the right eyes and served as contralateral controls. The eyes of all animals remained unwashed.

The eyes were examined for ocular reactions in accordance with the method of Draize at approximately 1, 24, 48, and 72 hours after dosing and on day 4 if irritation persisted. Sodium fluorescein was used to aid in revealing possible corneal damage at 24, 48, and 72 hours and on day 4. Postive conjunctival reactions were noted in the treated eye of 4 animals while minor conjuctival irritation was noted for all rabbits. There were no corneal or iridal findings. All irritation was reversible and completely subsided by day 4 or earlier.

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.

Justification : There was only 1 rabbit with a erythema score of 2.3 or more (mean values of 24, 48 and 72 hours). None of 6 rabbits have a oedema score of 2.3 or more. All effects were fully reversible.