Registration Dossier

Administrative data

Description of key information

A sample of was tested in the rabbit primary skin irritation/corrosion test to determine its possible irritating or corrosive effects. 
The flank skin of 3 female rabbits was exposed to 0.5 ml of the test substance for 4 hours using semi-occlusive dressing. This resulted in very slight, temporary oedema, and moderate erythema, which persisted for seven days in one animal and for two to three days in the other animals. The treated skin area of all animals showed scale formation from day 7 onwards. The mean values for eshar/erythema is =>1.5 and =< 2.3 for 2 out of 3 animals. The oedema score is < 1.5. Although the scoring does not warrant C&L the substance is classified as irritant because of the scaling observed from day 7 onwards.
The substance was tested, in the rabbit acute eye irritation/corrosion test to determine its possible irritating or corrosive effects. Instillation of 0.1 ml of the test substance in one of the eyes of three female rabbits resulted in slight redness and swelling of the conjunctivae. In two of the animals the conjunctival effects disappeared within twenty-four hours, whereas in one animal slight redness persi sted for forty-eight hours. No adverse effects on the cornea and the iris were observed in any of the rabbits during the entire observation period.

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:
06 May 1986 - 21 May 1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was performed according to OECD guidelines and GLP.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: The Broekman Institute, Someren, The Netherlands.
- Age at study initiation: animal 260: 09-12-1985, 8 to 10 weeks old; animal 295: 12-03-1986, 8 to 10 weeks old; animal 450: 10-04-1986, 12 to 14 weeks old.
- Weight at study initiation: see above
- Housing: They were individually housed in plastic cages with perforated floors.
- Diet (e.g. ad libitum):ad libitum, standard laboratory animal diet (100 g per day), obtained from Hope Farms, Woerden (LK-01, pellet diameter 4 mm)
- Water (e.g. ad libitum):ad libitum
- Acclimation period:7-days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22
- Humidity (%): 60-85
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 06 May 1986 - 21 May 1986
Type of coverage:
semiocclusive
Preparation of test site:
other: clipping
Vehicle:
unchanged (no vehicle)
Controls:
other: contralateral flank
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Concentration (if solution): as such

During dose administration the test substance was kept on ice.
Duration of treatment / exposure:
4 hours
Observation period:
The exposed skin areas were examined for signs of erythema and oedema and the responses were scored at 60 minutes, and approximately 24, 48 and 72 hours, and 7 and 14 days after removal of the patch. For reference the control site on the contralateral flank was used. In order to facilitate the scoring, the skin area concerned of animals no. 450 was shaved again before the observations on day 14.
Number of animals:
3 females
Details on study design:
TEST SITE
- Area of exposure: 6cm2
- % coverage: -
- Type of wrap if used: 6 cm2 gauze patch, which was attached with a drop of petrolatum to al uminium foil and mounted on permeable tape (Micropore, 3M, St. Paul, USA). This was applied to the right flank of each animal, the left flank being covered with the same dressing without testsubstance. Finally, the animals were wrapped in flexible bandage (Coban, 3M, St. Paul, USA).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): tissue moistened with tap-water.
- Time after start of exposure: 4 hours

SCORING SYSTEM:
Scoring system Erythema and oedema
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 edema(barely perceptible) 1
Slight edema(edges of the area well defined by definite raising) 2
Moderate edema(raised approximately 1mm) 3
Severe edema( raised more than 1 mm and extending beyond the area of exposure) 4

Irritation parameter:
erythema score
Basis:
mean
Remarks:
all animals
Time point:
other: 24-48-72 hours
Score:
1.88
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
mean
Remarks:
all animals
Time point:
other: 24-48-72 hours
Score:
0.44
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritant / corrosive response data:
The skin of the animals showed very slight oedema, persisting for 24 to 48 hours, and moderate erythema. In one of the animals (no. 260) the redness was still present 7 days after dosing, while the skin of animal 295 showed well-defined erythema for 3 days. In case of animal 450 the adverse skin effects had disappeared on day 3. Scale formation was observed on the treated skin area of all animals from day 7 onwards. Signs of systemic intoxication were not observed in any of the rabbits.
Other effects:
None

no.

Effect

Hour

Days after application

Mean score erythema

24/48/72 h

Mean score oedema

24/48/72 h

1

1

2

3

7

14

 

 

1

Erythema/ eschar

Oedema

2

 

2

2

 

1

2

 

1

2

 

0

2

 

0

0

 

0

2

 

 

0.67

2

Erythema/ eschar

Oedema

1

 

1

3

 

1

2

 

0

2

 

0

0

 

0

0

 

0

2.33

 

 

0.33

3

Erythema/ eschar

Oedema

1

 

1

3

 

1

1

 

0

0

 

0

0

 

0

0

 

0

1.33

 

 

0.33

Interpretation of results:
Category 2 (irritant)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The mean values for eshar/erythema is =>1.5 and =< 2.3 for 2 out of 3 animals. The oedema score is < 1.5. Although the scoring does not warrant C&L the substance is classified as irritant because of the scaling observed from day 7 onwards.
Executive summary:

A sample of was tested in the rabbit primary skin irritation/corrosion test to determine its possible irritating or corrosive effects.

The flank skin of 3 female rabbits was exposed to 0.5 ml of the test substance for 4 hours using semi-occlusive dressing. This resulted in very slight, temporary oedema, and moderate erythema, which persisted for seven days in one animal and for two to three days in the other animals. The treated skin area of all animals showed scale formation from day 7 onwards. Based on the scores that were obtained the substance is a mild skin irritant.

Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (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:
02 June 1986 - 05 June 1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was performed according to OECD guidelines and GLP.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: The Broekman Institute, Someren, The Netherlands
- Age at study initiation: approximately 10 weeks old
- Weight at study initiation: 2111, 2003 and 2407 grams
- Housing: indiVidually housed in metal cages with perforated floors
- Diet (e.g. ad libitum): ad libitum, standard laboratory animal diet (100 g per day), obtained from Hope Farms, Woerden (LK-01, pellet diameter 4 mm).
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5-21.5
- Humidity (%): 55-75
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 02 June 1986 - 05 June 1986
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Concentration (if solution): as such
Duration of treatment / exposure:
72 hours
Observation period (in vivo):
The eyes are examined 1, 24, 48, and 72 hours after instillation of the test substance. After recordi ng the observations at 24 hours, the eyes of the rabbi ts may be further examined with the aid of fluorescein stain. The untreated eye is used as reference. Another observations, generally performed on day 7, 14 and/or 21, may be needed in order to sufficiently evaluate reversibility or irreversibility.
Number of animals or in vitro replicates:
3 females
Details on study design:
SCORING SYSTEM:
Scoring system eye irritation

Cornea: degree of density (area most dense taken for reading)
0 No ulceration or opacity
1 Scattered or diffuse areas of opacity (other than slight dulling of normal lustre), details of iris clearly visible
2 Easily discernible translucent areas, details of iris slightly obscured
3 Nacrous areas, no details of iris visible, size of pupil barely discernible
4 Opaque cornea, iris not discernible through the opacity

Iris
0 Normal
1 Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia or injection, any of these or combination of any thereof, iris still reacting to light (sluggish reaction is positive)
2 No reaction to light, haemorrhage, gross destruction (any or all of these)

Conjunctivae
Redness (refers to palpebral and bulbar conjunctivae cornea and iris)
0 Blood vessels normal
1 Some blood vessels definitely hyperaemic
(injected)
2 Diffuse, crimson colour, individual vessels not easily discernible
3 Diffuse, beefy red

Chemosis (lids and/or nictitating membranes)
0 No swelling 0
1 Any swelling above normal (includes nictitating membranes)
2 Obvious swelling with partial eversion of lids
3 Swelling with lids about half-closed
4 Swelling with lids more than half-closed

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
1 animal
Time point:
other: 24-48-72
Score:
0.67
Max. score:
3
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: all other scores were 0 for 24-48-72 hours, see table below.
Irritant / corrosive response data:
One hour after dosing slight conjunctival redness and chemosis were observed in all animals; in two of them these effects disappeared wi thi n the next twenty-four hours, whereas in the third animal slight conjunctival hyperaemia was observed for forty-eight hours. Adverse effects on the cornea and the iris were not obse rved in any of the rabbits during the entire observation period. Treatment of the eyes with fluorescein 24 hours after instillation of the test substance did not reveal any epithelial damage. Signs of systemic intoxication were not observed.

Rabbit No and sex

Region of the eye

Hours after instillation

Average 24-48-72 hours

1

24

48

72

4-7-14(days)

 

1-f

Cornea

Degree of opacity

0

0

0

0

0

0

 

Iris

0

0

0

0

0

0

 

Conjunctivae

Redness

1

0

0

0

0

0

 

 

Chemosis

1

0

0

0

0

0

2-f

Cornea

Degree of opacity

0

0

0

0

0

0

 

Iris

 

0

0

0

0

0

0

 

Conjunctivae

Redness

1

0

0

0

0

0

 

 

Chemosis

1

0

0

0

0

0

3-f

Cornea

Degree of opacity

0

0

0

0

0

0

 

Iris

 

0

0

0

0

0

0

 

Conjunctivae

Redness

1

1

1

0

0

0.67

 

 

Chemosis

1

0

0

0

0

0

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
One hour after dosing slight conjunctival redness and chemosis were observed in all animals; in two of them these effects disappeared wi thi n the next twenty-four hours, whereas in the third animal slight conjunctival hyperaemia was observed for forty-eight hours (mean score 24-48-72 hours is 0.67). Therefore the substance is not classified as eye irritant.
Executive summary:

The substance was tested, in the rabbit acute eye irritation/corrosion test to determine its possible irritating or corrosive effects. Instillation of 0.1 ml of the test substance in one of the eyes of three female rabbits resulted in slight redness and swelling of the conjunctivae. In two of the animals the conjunctival effects disappeared within twenty-four hours, whereas in one animal sl ight redness persi sted for forty-eight hours. No adverse effects on the cornea and the iris were observed in any of the rabbits during the entire observation period.

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The registered substance, ±70% in phlegmatizer is a skin irritant and is not irritating to the eye.


Justification for selection of skin irritation / corrosion endpoint:
K1: The study was performed according to OECD guidelines and GLP.

Justification for selection of eye irritation endpoint:
K1: The study was performed according to OECD guidelines and GLP.

Effects on skin irritation/corrosion: irritating

Justification for classification or non-classification

Based on the results an in vivo skin and eye irritation study in rabbits, the substance is classified as a cat. 2 skin irritant.