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Administrative data

Description of key information

Skin irritation: A single semi-occlusive application of D.I.X.T. to intact rabbit skin for four hours elicited well-defined to moderate dermal irritation, but not sufficient for classification as an irritant.
Eye irritation: Instillation of D.I.X.T. into the rabbit eye did not elicit a positive response in any of the six treated animals according to the test guideline criteria.

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:
Study was undertaken between 7 and 21 January 1986.
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted in accordance with generally accepted scientific principles, possibly with incomplete or methodological deficiencies, which do not affect the quality of relevant results.
Qualifier:
according to
Guideline:
EPA OTS 798.4470 (Acute Dermal Irritation)
Deviations:
no
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Obtained from Froxfield Rabbits, Petersfield, Hampshire.
- Age at study initiation: Approximately 11 to 13 weeks of age.
- Weight at study initiation: Weight range 2.4 to 3.0 kg, prior to treatment on Day 1
- Housing: The rabbits were individually housed in metal cages with perforated floors
- Diet (e.g. ad libitum): Free access to SDS Standard Rabbit Diet.
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: The rabbits selected for the study were all acclimated to the laboratory environment.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Room temperature was maintained at approximately 19°C.
- Humidity (%): Relative humidity at 30-70%.
- Air changes (per hr): Air exchange was maintained at approximately 19 air changes per hour.
- Photoperiod (hrs dark / hrs light): Lighting was controlled by means of a time switch to give 12 hours of artificial light (0700-1900 hours) in each 24 hour period.

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): A 0.5 ml aliquot of D.I.X.T. was applied.

Duration of treatment / exposure:
SIngle application for a four hour period.
Observation period:
Examination of the treated skin was made on Day 1 (i.e. approximately 30 minutes after removal of the patches) and on Days 2, 3 and 4. Additional observations were made on Days 5 through 14.
Number of animals:
6
Details on study design:
TEST SITE
Approximately 24 hours prior to application of the test substance, hair was removed with electric clippers from the dorso-lumbar region of each rabbit exposing an area of skin approximately 10 cm square.

A 0.5 ml aliquot of D.I.X.T. was applied under a 2.5 cm square gauze pad to one intact skin site on each animal.

Each treatment site was occluded with "Elastoplast" elastic adhesive dressing for a four hour period. The animals were not restrained during the exposure period and were returned to their cages.

REMOVAL OF TEST SUBSTANCE
At the end of the exposure period, the semi-occlusive dressing and gauze pad were removed and the treatment site was washed using distilled water to remove any residual test substance.

SCORING SYSTEM:
Grading and scoring of the dermal reactions were performed using the prescribed numerical scoring system as follows:

Erythema and eschar formation:
No erythema: 0
Very slight erythema (barely perceptible): 1
Well-defined erythema: 2
Moderate to severe erythema: 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth): 4

Oedema formation:
No oedema: 0
Very slight oedema (barely perceptible): 1
Slight oedema (edges of area well-defined by definite raising): 2
Moderate oedema (raised approximately 1 millimetre): 3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure): 4

Any other lesion not covered by this scoring system, will be described.







Irritation parameter:
erythema score
Basis:
mean
Remarks:
Mean of all animals (6 in total) scores for erythema
Time point:
24/48/72 h
Score:
1.5
Max. score:
4
Reversibility:
other: Erythema persisted up to day 14 in 4 animals. 2 animals showed no effects after 4 days.
Irritation parameter:
edema score
Basis:
mean
Remarks:
Mean of all animals (6 in total) scores for oedema
Time point:
24/48/72 h
Score:
1.1
Max. score:
4
Reversibility:
other: Oedema persisted up to day 14 in 4 animals. 2 animals showed no effects after 4 days.
Irritant / corrosive response data:
The numerical scores awarded to the dermal reactions elicited by D.I.X.T. are given in Table 1.

Very slight erythema and oedema was observed in all six rabbits following removal of the bandages on Day 1. Very slight to well-defined erythema with or without very slight oedema was seen in all six rabbits on Day 2. These reactions ameliorated in two animals and had resolved completely by Day 4 in these animals.

Well-defined erythema with slight to moderate oedema developed in the four remaining animals.

Well-defined dermal reactions persisted in four animals at Day 14.

Desquamation of the stratum corneum was seen in three animals.

Table 1: Dermal reaction elicited by DIXT

Rabbit Number (male)

E= Erythema

O – Oedema

Day

1*

2

3

4

5

6

7

8

9

10

11

12

13

14

1101

E

O

1

1

1

1

2

1

2

2

2

2

2

2

2A

2

2A

2

2

2

2

2

1

2

1

2

1

2

1

2

1102

E

O

1

1

2

1

2

2

2

2

2

2

2

2

2A

2

2A

2

2

2

2

1

2

2

2

2

1

2

1

2

1103

E

O

1

1

2

1

1

1

0

0

 

 

 

 

 

 

 

 

 

 

1104

E

O

1

1

1

1

2

1

2

2

2

2

2

2

1

2

1

2

1

2

1

1

1

2

2

2

2

2

2

2

1105

E

O

1

1

1

0

1

0

0

0

 

 

 

 

 

 

 

 

 

 

1106

E

O

1

1

1

1

2

2

2

2

2

2

2

2

2A

3

2

3

2

3

2

3

2

2

2

2

2

2

2

2

* Approximately 30 minutes after removal of the dressing

A: Desquamation of the stratum corneum.

Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
A single semi-occlusive application of D.I.X.T. to intact rabbit skin for four hours elicited well-defined to moderate dermal irritation.
Executive summary:

Introduction:

The experimental procedure used followed the Testing Guidelines as described in the Federal Register, Vol. 50, No. 188, Part 11 of 27 September 1985, Section 798.4470 - Primary Dermal Irritation.

Results:

A single 4-hour, semi-occluded application of the test item to the intact skin of 6 New Zealand White strain rabbits produced the following results:

Very slight erythema and oedema was observed in all six rabbits following removal of the bandages on Day 1. Very slight to well-defined erythema with or without very slight oedema was seen in all six rabbits on Day 2. These reactions ameliorated in two animals and had resolved completely by Day 4 in these animals.

Well-defined erythema with slight to moderate oedema developed in the four remaining animals.

Well-defined dermal reactions persisted in four animals at Day 14.

Desquamation of the stratum corneum was seen in three animals.

Conclusion:

A single semi-occlusive application of D.I.X.T. to intact rabbit skin for four hours elicited well-defined to moderate dermal irritation.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (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:
Study was undertaken between 6 and 13 January 1986.
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted in accordance with generally accepted scientific principles, possibly with incomplete or methodological deficiencies, which do not affect the quality of relevant results.
Qualifier:
according to
Guideline:
EPA OTS 798.4500 (Acute Eye Irritation)
Deviations:
no
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Obtained from Froxfield Rabbits, Petersfield, Hampshire.
- Age at study initiation: Approximately 10 to 13 weeks of age.
- Weight at study initiation: Weight range 2.3 to 3.0 kg, prior to treatment on Day 1
- Housing: The rabbits were individually housed in metal cages with perforated floors
- Diet (e.g. ad libitum): Free access to SDS Standard Rabbit Diet.
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: The rabbits selected for the study were all acclimated to the laboratory environment.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Room temperature was maintained at approximately 19°C.
- Humidity (%): Relative humidity at 30-70%.
- Air changes (per hr): Air exchange was maintained at approximately 19 air changes per hour.
- Photoperiod (hrs dark / hrs light): Lighting was controlled by means of a time switch to give 12 hours of artificial light (0700-1900 hours) in each 24 hour period.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
A 0.1 ml aliquot of D.I.X.T. was placed into the lower everted lid of one eye of each animal.

The eyelids were then gently held together for one second before releasing. The contralateral eye remained untreated and served as a control.

Duration of treatment / exposure:
Single application.
Observation period (in vivo):
Examination of the eyes was made after 1 hour and 1, 2, 3, 4 and 7 days after instillation.
Number of animals or in vitro replicates:
6
Details on study design:
SCORING SYSTEM:
Grading and scoring of the ocular lesions were performed using the numerical scoring system (Draize) as shown in attached background material):

TOOL USED TO ASSESS SCORE:Observation of the eyes was aided by the use of a handheld torch.
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Remarks:
(Animal 1155)
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 3 days
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Remarks:
(Animal 1156)
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 2 days
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Remarks:
(Animal 1157)
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 4 days
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Remarks:
(Animal 1158)
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 3 days
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Remarks:
(Animal 1159)
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 2 days
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Remarks:
(Animal 1160)
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 2 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
(Animal 1155)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
(Animal 1156)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
(Animal 1157)
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 2 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
(Animal 1158)
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 2 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
(Animal 1159)
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 2 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
(Animal 1160)
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 2 days
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
(all animals)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
(all animals)
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritant / corrosive response data:
The numerical scores awarded to the ocular reactions elicited by D.I.X.T. are given in Table 1 (see attached background material).

None of the animals gave a "positive" response.

No corneal damage or iridial inflammation was seen in any of the animals.

Mild conjunctival reactions were observed in all six animals.

The eyes were normal two to four days after instillation.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Instillation of D.I.X.T. into the rabbit eye did not elicit a positive response in any of the six treated animals.
Executive summary:

Introduction.

The experimental procedure used followed the Testing Guidelines described in the Federal Register, Vol. 50, No.188, Part II of 27 September 1985 Section 798.4500 - Primary Eye Irritation.

Result.

A single application of the test item to the eye of six New Zealand White strain rabbits produced the following results:

None of the animals gave a "positive" response according to the test guideline criteria.

No corneal damage or iridial inflammation was seen in any of the animals.

Mild conjunctival reactions were observed in all six animals.

The eyes were normal two to four days after instillation.

Conclusion.

Instillation of D.I.X.T. into the rabbit eye did not elicit a positive response in any of the six treated animals according to the test guideline criteria.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin Irritation:

Introduction:

The experimental procedure used followed the Testing Guidelines as described in the Federal Register, Vol. 50, No. 188, Part 11 of 27 September 1985, Section 798.4470 - Primary Dermal Irritation.

Results:

A single 4-hour, semi-occluded application of the test item to the intact skin of 6 New Zealand White strain rabbits produced the following results:

Very slight erythema and oedema was observed in all six rabbits following removal of the bandages on Day 1. Very slight to well-defined erythema with or without very slight oedema was seen in all six rabbits on Day 2. These reactions ameliorated in two animals and had resolved completely by Day 4 in these animals.

Well-defined erythema with slight to moderate oedema developed in the four remaining animals.

Well-defined dermal reactions persisted in four animals at Day 14.

Desquamation of the stratum corneum was seen in three animals.

Conclusion:

A single semi-occlusive application of D.I.X.T. to intact rabbit skin for four hours elicited well-defined to moderate dermal irritation.

Eye Irritation:

Introduction.

The experimental procedure used followed the Testing Guidelines described in the Federal Register, Vol. 50, No.188, Part II of 27 September 1985 Section 798.4500 - Primary Eye Irritation.

Result.

A single application of the test item to the eye of six New Zealand White strain rabbits produced the following results:

None of the animals gave a "positive" response according to the test guideline criteria.

No corneal damage or iridial inflammation was seen in any of the animals.

Mild conjunctival reactions were observed in all six animals.

The eyes were normal two to four days after instillation.

Conclusion.

Instillation of D.I.X.T. into the rabbit eye did not elicit a positive response in any of the six treated animals according to the test guideline criteria.

Respiratory irritation:

As the substance has shown evidence of causing some irritation effects and is a skin sensitiser, it can be assumed that it may have the potential cause respiratory irritation if inhaled.


Justification for selection of skin irritation / corrosion endpoint:
Study conducted in accordance with generally accepted scientific principles, possibly with incomplete or methodological deficiencies, which do not affect the quality of relevant results. The study has been assigned a reliability 2 and is the only available skin irritation study.

Justification for selection of eye irritation endpoint:
Study conducted in accordance with generally accepted scientific principles, possibly with incomplete or methodological deficiencies, which do not affect the quality of relevant results. The study has been assigned a reliability 2 and is the only available eye irritation study.

Effects on skin irritation/corrosion: slightly irritating

Justification for classification or non-classification

Skin irritation:

The skin irritation study showed the substance to cause some irritating effects, but these have been considered to not be sufficient to cause classification.

The mean scores for erythema and oedema, calculated for each individual animal (using the scores at Days 2, 3 and 4) were all below the CLP criteria for classification of ≥2.3 to ≤4.0. The mean scores for all animals combined was 1.5 for erythema and 1.1 for oedema.

Irritation persisted until the end of the study (Day 14) in 4 of the 6 animals. This would potentially mean classification was applicable under the CLP criteria, however classification has not been considered appropriate in this case taking into account the nature of the effects observed throughout the study.

The substance and skin irritation study have previously been reviewed by the UK HSE with regards to whether classifcation and labelling as a skin irritant was applicable. The conclusion was that the substance should not be classified as a skin irritant. It is considered that some of the irriation caused by the substance may be due to the sulfur impurity.

A classification for skin irritation has therefore not been applied. However, the substance should be considered to have the potential to cause some dermal irritation effects if exposure occurs.

Eye irritation:

The results of the eye irritation study have been assessed against the CLP regulation criteria for reversible eye effects (Irritating to eyes Category 2). According to this criteria a substance produce a postive response when

- corneal opacity ≥1 and/or

- iritis ≥1, and/or

- conjunctival redness ≥ 2, and/or

- conjunctival oedema (chemosis) ≥ 2

calculated as the mean scores following grading at 24, 48 and 72 hours.

No corneal damage or iridial inflammation was seen in any of the animals. The maximum mean score for redness in any animal was 0.67. The maximum mean score for chemosis in any animals was 0.33. All effects were fully reversible within 2 to 4 days.

It is therefore concluded that the CLP criteria for classification is not met.