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Description of key information

 An in vivo skin and an eye irritation study have been performed according to OECD/EC testguidelines and GLP principles, showing minimal skin irritation and highly irritating effects in the eye.

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:
18Jan-25Jan 1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles.
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1981
Deviations:
yes
Remarks:
, According to 2002 adopted guideline, three animals were tested simultaneously instead of successively. Substance applied to the skin occlusively instead of semi-occlusively. These deviations do not influence the reliability of the results.
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
1984
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
- Source: ENKI-Konijnenfarm, Someren, The Netherlands
- Age at study initiation: Young adult animals
- Weight at study initiation: 2881 ± 57g
- Housing: individually housed in suspended, galvanized cages fitted with a mire-mesh floor and front
- Diet: Free access to standard laboratory rabbit diet
- Water: Free access to tap water.
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18± 3°C
- Humidity (%): at least 40%
- Air changes (per hr): approx 10
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 g per sample (approximately 0.5ml)
Duration of treatment / exposure:
single 4-hours
Observation period:
7 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 1 inch x 1 inch (approximately 6.54 cm2)
- Type of wrap if used: impervious material

REMOVAL OF TEST SUBSTANCE
- Washing: yes, with lukewarm water and soap
- Time after start of exposure: 4 hours

SCORING SYSTEM: resulting skin reactions were evaluated by the method of Draize et al (J. Exp. Pharmacol. Exp. Ther. 82 (1944)
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 24, 48 and 72 hours after wash
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 24, 48, 72 hours after wash
Score:
0
Max. score:
4
Remarks on result:
other: no edema observed at any timepoint
Irritant / corrosive response data:
No edema observed at any time point, same observation for both batches used.
Two out of three rabbits showed very slight erythema (barely perceptible) at 1, 24, 48 and 72 hours after wash, same observation for both batches used. After 7 days, no irritation observed anymore.
Other effects:
At 48 and 72 hours after patch removal, very slight scaliness was observed in all (three) rabbits. Effect disappeared after 7 days.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In a skin irritation study with rabbits performed according to OECD/EC-standards, the test substance is not irritating or corrosive to the skin.
Executive summary:

In an acute dermal irritation/ corrosion study two batches of CX-100 were applied to shaven skin of rabbits. The substances were kept on the skin for 4 hours (occlusive) and washed of with lukewarm water and soap. In the observation period (1h, 24, 48, 72 hours after wash, total observation period = 1 week), no edema was observed in any of the rabbits. Two of the three rabbits showed very slight erythema (barely perceptible) starting one hour after wash until 72 hours after wash, that was reversible within 1 week. Both batches showed the same response. On the basis of the results it is concluded that, under the conditions of this study, the test substance is not irritating or corrosive to the skin.

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:
22 Jun 2000- Nov 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The experiment was conducted according to current EC/OECD guidelines in compliance with GLP standards.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
2002
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Myrtle's rabbitry, Thompson Station, TN
- Age at study initiation: appr. 15 weeks
- Weight at study initiation: 2.9-3.5kg (m)/ 2.8-3.5kg (f)
- Housing: individually, in suspended stainless steel cages
- Diet: ad libitum, PMI Certified Rabbit Chow #5322 (Purina Mills, Inc.)
- Water: ad libitum, purified tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-21
- Humidity (%): 42-80
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: July 10, 2000 To: July 31, 2000
Vehicle:
unchanged (no vehicle)
Controls:
other: the contralateral eye remained untreated
Amount / concentration applied:
0.1ml
Duration of treatment / exposure:
Single instillation
Observation period (in vivo):
1, 24, 48, 72 hours and up to 7 days
Number of animals or in vitro replicates:
3 males, 3 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: no. In addition to the 6 rabbits whose eyes were not rinsed, 3 females were treated with 0.1ml of the test substance and subsequently the eyes were rinsed (30s after instillation) with sterile water. These animals were observed up to 21 days.

SCORING SYSTEM:
Ocular grading system according to Draize; details described in OECD guideline

OBSERVATIONS:
- General health and mortality was monitored twice daily.

TOOL USED TO ASSESS SCORE: lamp / fluorescein
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
mean
Remarks:
of 6 animals
Time point:
other: 24, 48 and 72 hours
Score:
ca. 3.4
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: 2/6 rabbits had severe swelling that hampered ocular inspection at 24 hours.
Irritation parameter:
iris score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: 48 and 72 hours
Score:
ca. 1.1
Max. score:
2
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: For none of the rabbits the iris score could be assessed at 24 hours due to severe swelling.
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
mean
Remarks:
of 6 animals
Time point:
other: 24, 48 and 72 hours
Score:
2.8
Max. score:
3
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: 24, 48 and 72 hours
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
Discharge
Basis:
mean
Remarks:
of 6 animals
Time point:
other: 24, 48 and 72 hours
Score:
2.2
Max. score:
3
Reversibility:
not fully reversible within: 7 days
Irritant / corrosive response data:
The eyes of animals with rinsed eyes were only exposed for 30s. The following scores were obtained (where possible, based on observations at 24, 48 and 72 hours):
Cornea: ca. 2.6 (one animal's eye too swollen at t=48 hours to be assessed)
Iris: ca. 1.2 (one animal's eye too swollen to be assessed)
Conjunctivae- redness: ca. 2.8
Chemosis: ca. 4
Conjunctivae- discharge: ca. 2.3
After 21 days, effects were not reversed.
Other effects:
In the group of animals without rinsing of the eyes slight hairloss around the treated eye was observed in 2 males and 2 females. One male showed head tilt on days 0-2.
The three females whose eyes were rinsed also showed hairloss around the treated eye (slight to moderate). Two females showed head tilt on days 0-2.

Interpretation of results:
Category 1 (irreversible effects on the eye)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
An eye irritation study according to current OECD/EC guidelines was conducted in compliance with GLP principles. Based on the results of this study, the substance has to be classified category 1 causing "irreversible effects on the eye/ serious damage to eyes" according to CLP Regulation (EC) No. 1272/2008.
Executive summary:

An eye irritation study according to current OECD/EC guidelines was conducted in compliance with GLP principles. In this study, 6 rabbits (3 males and 3 females) showed severe effects on the eyes the first 72 hours after treatment, which did not reverse after one week. In parallel, three females were treated with the substance, which was removed from the eye after 30s by rinsing. The effects to the eyes of these animals were comparable to the eyes of the unrinsed group. The effects did not reverse within 21 days after treatment. Additionally, three treated animals (two with rinsed and one with unrinsed eyes) showed tilting of the head, Seven rabbits showed slight hairloss around the treated eye. Based on the results of this study, the substance has to be classified with category 1, H318, causing "irreversible effects on the eye/ causes serious eye damage" according to CLP Regulation (EC) No. 1272/2008.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin:

In an acute dermal irritation/ corrosion study two batches of the test substance were applied to shaven skin of rabbits. The substances were kept on the skin for 4 hours (occlusive) and washed of with lukewarm water and soap. In the observation period (1h, 24, 48, 72 hours after wash, total observation period = 1 week), no edema was observed in any of the rabbits. Two of the three rabbits showed very slight erythema (barely perceptible) starting one hour after wash until 72 hours after wash, that was reversible within 1 week. Both batches showed the same response. On the basis of the results it is concluded that, under the conditions of this study, the test substance is not irritating or corrosive to the skin.

Eye irritation study:

An eye irritation study according to current OECD/EC guidelines was conducted in compliance with GLP principles. In this study, 6 rabbits (3 males and 3 females) showed severe effects on the eyes the first 72 hours after treatment, which did not reverse after one week. In parallel, three females were treated with the substance, which was removed from the eye after 30s by rinsing. The effects to the eyes of these animals were comparable to the eyes of the unrinsed group. The effects did not reverse within 21 days after treatment. Additionally, three treated animals (two with rinsed and one with unrinsed eyes) showed tilting of the head, Seven rabbits showed slight hairloss around the treated eye.


Justification for selection of skin irritation / corrosion endpoint:
Only one study available performed according to OECD guidelines and GLP principles with a reliability score of 1.

Justification for selection of eye irritation endpoint:
Only one study available performed according to OECD guidelines and GLP principles with a reliabilty score of 1.

Effects on eye irritation: highly irritating

Justification for classification or non-classification

Based on the available data the substance does not have to be classified according to CLP Regulation (EC) No. 1272/2008 for skin irritation.

Based on the available data the substance is classified according to CLP Regulation (EC) No. 1272/2008 for eye irritation Category 1, H318, causing "irreversible effects on the eye/ causes serious eye damage".