Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Skin irritation/corrosion: not irritating
Eye irritation: slightly irritating but not classify

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 23 september 1992 To 26 September 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study
Qualifier:
according to guideline
Guideline:
EPA OPP 81-5 (Acute Dermal Irritation)
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
Draize test.
GLP compliance:
yes (incl. QA statement)
Specific details on test material used for the study:
Purity of the test material is based on the phosphonate composition, with no direct measure of % sodium. ITC 288 is not the "Reaction mass of tetrasodium-phosphonoethane-1,2-dicarboxylate and hexasodium-phosphonobutane-1,2,3,4--tetracarboxylate" (EC 410-800-5) rather the substance "Reaction mass of trisodium-phosphonoethane-1,2-dicarboxylate and pentasodium-phosphonobutane-1,2,3,4--tetracarboxylate" (EC 701-079-0) as demonstrated by the manufacturing specs reported in Section 1.2, legal entity composition.
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, U.K.
- Age at study initiation: 12-16 weeks old
- Weight at study initiation: 2.31-2.82 kg
- Housing: individually in suspended metal cages
- Diet : ad libitum (Spillers Rabbit Diet, Dalgety Agriculture Ltd., Almondsbury, Bristol, U.K.)
- Water : ad libitum
- Acclimation period: at least five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-21
- Humidity (%): 56-58
- Air changes (per hr): 15
- Photoperiod : 12 hrs dark / 12 hrs light


IN-LIFE DATES: From: 23 September 1992 To: 26 September 1992
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

VEHICLE: none
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
6 males
Details on study design:
TEST SITE
- Area of exposure: dorsal/flank area
- % coverage: no data
- Type of wrap if used: elasticated corset (TUBIGRIP)


REMOVAL OF TEST SUBSTANCE
- Washing (if done): any residual test material were removed by gentle swabbing with cotton wool soaked in distilled water.
- Time after start of exposure: no data


SCORING SYSTEM: according to the Draize scale
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48, and 72 hr
Score:
0
Max. score:
4
Irritant / corrosive response data:
Very slight erythema was noted at three treated skin sites one hour after patch removal. all treated skin sites appeared normal 24 hours after treatment.
Other effects:
None

Table 7.3.1/1: Irritant/corosive response data for each male animal after 4h exposure under semiocclusive coverage

score at time point/ Reversibility Erythema
Max. score:4
Edema
Max. score:2
1h 1/0/0/1/0/1 0/0/0/0/0/0
24h 0/0/0/0/0/0 0/0/0/0/0/0
48h 0/0/0/0/0/0 0/0/0/0/0/0
72h 0/0/0/0/0/0 0/0/0/0/0/0
Average 24h, 48h, 72h 0 0
Interpretation of results:
not irritating
Remarks:
according to the CLP Regulation (EC n.1272/2008)
Conclusions:
Under the conditions of this test, ITC 288 was non-irritant to rabbit skin. Therefore, no classification is required according to the EU legislation (CLP regulation (1272/2008) and Directive 67/548/EEC).
Executive summary:

In a primary dermal irritation study (Tuffnell, 1992), six male New Zealand rabbits were dermally exposed to 0.5 g of ITC 288, moistened with 0.5 ml of distilled water for 4 hours under an semi-occlusive dressing. Animals were observed for 3 days. Irritation was scored by the draize scale. A single 4-hour, semi-occluded application of ITC 288 to the intact skin of six rabbits produced very slight erythema. All treated skin sites appeared normal after treatment. Mean scores (24, 48, 72 hours) was 0.0 for erythema and edema. Under the test conditions of this study, ITC 288 is not considered as skin irritant according to the EU legislation (CLP regulation (1272/2008) and Directive 67/548/EEC).

This skin irritation study is classified as acceptable. It satisfies the guideline requirement for a skin irritation in the rabbit.

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:
From 12 October 1992 To 16 October 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study
Qualifier:
according to guideline
Guideline:
EPA OPP 81-4 (Acute Eye Irritation)
Deviations:
no
Principles of method if other than guideline:
Draize test.
GLP compliance:
yes (incl. QA statement)
Specific details on test material used for the study:
Purity of the test material is based on the phosphonate composition, with no direct measure of % sodium. ITC 288 is not the "Reaction mass of tetrasodium-phosphonoethane-1,2-dicarboxylate and hexasodium-phosphonobutane-1,2,3,4--tetracarboxylate" (EC 410-800-5) rather the substance "Reaction mass of trisodium-phosphonoethane-1,2-dicarboxylate and pentasodium-phosphonobutane-1,2,3,4--tetracarboxylate" (EC 701-079-0) as demonstrated by the manufacturing specs reported in Section 1.2, legal entity composition.
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheschire, U.K.
- Age at study initiation: 12-16 weeks old
- Weight at study initiation: 2.61-3.18 kg
- Housing: individually
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-19
- Humidity (%): 53-55
- Air changes (per hr): 15
- Photoperiod : 12 hrs dark / 12 hrs light


IN-LIFE DATES: From: 12 October 1992 To: 16 October 1992
Vehicle:
not specified
Controls:
other: left eye was used for control purposes
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): a volume of 0.1 ml of the test material, which was found to weight approximately 93 mg was placed into the conjunctival sac of the right eye
Duration of treatment / exposure:
not rinsed
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
6 (4 males and 2 females)
Details on study design:

SCORING SYSTEM: Draize scale for scoring ocular irritation


TOOL USED TO ASSESS SCORE: examination of the eye was facilitated by use of the light source from a standard ophtalmoscope
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48, 72 hr
Score:
0.28
Max. score:
4
Reversibility:
fully reversible within: 72 hr
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48 and 72 hr
Score:
0.17
Max. score:
2
Reversibility:
fully reversible within: 24 hr
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48 and 72 hr
Score:
0.83
Max. score:
3
Reversibility:
fully reversible within: 72 hr
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24,48 and 72 hr
Score:
0.55
Max. score:
4
Reversibility:
fully reversible within: 72 hr
Irritant / corrosive response data:
A single application of the test material to a right eye of six rabbits produced diffuse corneal opacity, iridial inflammation and moderate conjunctival irritation. Dulling of the normal lustre of the corneal surface was confined to one treated eye one hour after treatment. All treated eyes appeared normal 72 hours after treatment.
Other effects:
None

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
Max. score:4
Iris
Max. score:2
Conjunctivae
Max. score:3
Chemosis
Max. score:4
1h 0/0/0/d/0/0 1/1/1/1/1/1 2/2/2/2/2/2 2/2/2/2/2/2
24h 0/0/1/1/1/0 0/0/1/1/1/0 2/1/2/1/2/1 1/1/2/1/1/1
48h 0/0/1/1/0/0 0/0/0/0/0/0 1/1/1/1/1/1 1/0/1/0/1/0
72h 0/0/0/0/0/0 0/0/0/0/0/0 0/0/0/0/0/0 0/0/0/0/0/0
Average 24h, 48h, 72h 0.28 0.17 0.83 0.55
 Reversibility *)  c.  c.  c.  c.

d = dulling of the normal lustre of the corneal surface

c. = completely reversible

Interpretation of results:
slightly irritating
Remarks:
according to the CLP Regulation (EC n.1272/2008)
Conclusions:
Under the conditions of this test, ITC 288 is slightly irritating to eyes. However, no classification is required according to the EU legislation (CLP regulation (1272/2008) and Directive 67/548/EEC).
Executive summary:

In a primary eye irritation study (Tuffnell, 1992), six New Zealand rabbits were exposed to ITC 288. Animals were observed for 3 days. Irritation was scored by the draize scale. Dulling of the normal lustre of the cornea surface was noted in one treated eye one hour after treatment. Diffuse corneal opacity was noted in three treated eyes at the 24 -hour observation and in two treated eyes at the 48 -hour observation. No other adverse corneal effects were noted. Iridial inflammation was noted in all treated eyes one hour after treatment and in three treated eyes at the 24 -hour observation. No other adverse iridial effects were noted. Moderate conjunctival irritation was noted in all treated eyes one hour after treatment with minimal to moderate conjunctival irritation at the 24 -hour observation and minimal conjunctival irritation at the 48 -hour observation. All treated eyes appeared normal 72 -hours after treatment. A single application of ITC 288 to the intact eye of six rabbits produced mild irritation which desappeared. Under the test conditions of this study, ITC 288 is slightly irritating to eyes but no classification is required according to the EU legislation (CLP regulation (1272/2008) and Directive 67/548/EEC).

This eye irritation study is classified as acceptable. It satisfies the guideline requirement for an eye irritation study in the rats.

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

Additional information

1- Skin irritation / corrosion:

Two studies were available with reliability 1 and 2 according to Klimisch rating (Kr).

- A key study was identified (Tuffnell, 1992). This study was performed similarly to the OECD test guideline No. 404 and in compliance with GLP (Kr: 1). Six New Zealand rabbits were dermally exposed to 0.5 g of ITC 288/S moistened with 0.5 ml of distilled water for 4 hours under an semi-occlusive dressing. Animals were observed for 3 days. Irritation was scored by the draize Scale. All treated skin sites appeared normal after treatment. Mean scores (24, 48, 72 hours) was 0.0 for erythema and edema. Therefore, ITC 288/S is considered as not irritating to the skin.

- A study report (Cuthbert and Jackson, 1991) has been chosen as supporting study. This study was performed similarly to the OECD test guideline No. 404 and in compliance with GLP (Kr: 2). Three New Zealand rabbits were dermally exposed to 0.5 mL of ITC 288/S. Test sites were covered with an semi-occlusive dressing for 4 hours and were washed after the patch removal. Animals were observed for 3 days. Irritation was scored using the OECD Recommended Scoring System. Mean scores per animal (24, 48 and 72 hours) was 0.0 for erythema and edema

Taken together these results show that ITC 288/S is not irritating to the skin

2- Eye irritation:

One study was available for this endpoint and considered as the key study (Tuffnell, 1992). This study was performed similarly to the OECD test guideline No. 405 and in compliance with GLP (Kr: 1), 0.1 mL of ITC 288/S was instilled into the conjunctival sac of the right eye of six New Zealand rabbits. The eyes of the animals were not rinsed after instillation. Changes were observed at 1, 24, 48 and 72 hours after dosing and grading according to Draize scale. ITC 288/S produced chemosis (mean score 0.55), conjunctival redness (mean score 0.83), corneal lesions (mean score 0.28) and iridial lesions (mean score 0.17) which were completely reversed after 3 days. Thus, ITC 288/S is considered as slightly irritating to the eyes.

3- Respiratory irritation:

No data was available.


Effects on eye irritation: slightly irritating

Justification for classification or non-classification

1- Skin irritation / corrosion:

As no signs of irritation were observed in two dermal irritation studies with ITC 288/S conducted similarly to OECD test guideline No. 404 (Mean scores (24, 48 and 72 hours) were 0.0 for erythema and edema), ITC 288/S is not classified as irritating to the skin according to the EU legislation (Directive 67/548/EEC and the CLP Regulation (1272/2008)).

2- Eye irritation:

ITC 288/S is slightly irritating to the eyes in a primary eye irritation study conducted similarly to OECD test guideline No. 405. Mean scores (24, 48 and 72 hours) were 0.55, 0.83, 0.28 and 0.17 for chemosis, conjunctival redness, corneal lesions and iridial lesions respectively. All these effects were completely reversed after 3 days. Therefore, no classification is required according to the EU legislation (Directive 67/548/EEC and the CLP Regulation (1272/2008)).

3- Respiratory irritation:

No classification is possible due to lack of data

Categories Display