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Description of key information

 The reaction mass of Stearoylbenzoylmethane and Palmitoylbenzoylmethane is not classified as a skin or eye irritant.

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 8-FEB-94 to 11-FEB-94
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Test procedure in accordance with OECD guideline standard method and Good Laboratory Practice. No information on purity of batch of test substance but company documentation is available.
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
not specified
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: Elevage Cunicole de Val de Selle (80160 Prouzel), France
- Age at study initiation: no data
- Weight at study initiation: 2.5 +- 0.3 kg
- Housing: individually in polystyrene cages (35 x 55 x 32 cm) in an environmentally controlled room
- Diet: UAR "112 C" pelleted diet (UAR, 91360 Villemoisson-sur-Orge, France), ad libitum. (composition and contaminants analysis by the supplier.
- Water: filtered drinking water (0.22 µm), ad libitum. Bacteriological and chemical analysis performed periodically.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS:
- Temperature: 18 +- 3°C
- Humidity: 30-70 %
- Air changes: no data
- Photoperiod: 12h light-dark cycle

IN-LIFE DATES: from 8-FEB-1994 to 11-FEB-1988
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: not required since untreated left flank served as negative control
Amount / concentration applied:
TEST MATERIAL
-Amount applied (volume or weight with unit): 0.5 g of test substance as supplied
-Concentration (if solution): /
-pH: 4.6 (analysis at CIT)

Duration of treatment / exposure:
4 hours
Observation period:
Observation at 1, 24, 48 and 72 hours (in the absence of dermal irritation, the study is ended at 72 hours).
Number of animals:
6
Details on study design:
TEST SITE:
- Area of exposure: one square inch (6 cm2)
- % coverage: data not available
- Type of wrap if used: gauze patch was kept in skin contact with an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage.

REMOVAL OF TEST SUBSTANCE:
- Washing: no residual test substance was observed
- Time after start of exposure: 4 hours

SCORING SYSTEM: in accordance with Draize scale
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: Over 24 to 72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: Very slight erythema (score 1) was observed only on one skin site at the 1-hour reading.
Irritation parameter:
edema score
Basis:
mean
Time point:
other: Over 24h to 72h.
Score:
0
Max. score:
4
Reversibility:
other: no edema observed at any time

Table 7.3.1/1: 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

Erythema

Edema

Max. score: 4

Max. score: 4

24 h

0/0/0

0/0/0

48 h

0/0/0

0/0/0

72 h

0/0/0

0/0/0

Average 24h, 48h, 72h

0-0-0

0-0-0

 Reversibility  NA  NA

NA: Not applicable

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The reaction mass of Stearoylbenzoylmethane and Palmitoylbenzoylmethane is not classified as a skin irritant according to the criteria of annex VI of the Directive 67/548/CEE and according to EU Regulation 1272/2008 (CLP).
Executive summary:

RHODIASTAB X5 has been tested for acute skin irritation on 3 male New Zealand White rabbits, according to O.E.C.D. guideline Nb.404 and Directive 67/548/EEC and in compliance with Good Laboratory Practice. The test substance was applied as supplied, on a compress moistened with water, in a single dermal dose of 0.5 g, to a 6 cm2clipped area of the right flank skin during 4 hours under a semi-occlusive dressing. The untreated left flank served as negative control. The cutaneous examinations were performed 1, 24, 48 and 72 hours after removal of the dressing.

No edema was noted. Erythema score 1 was observed only at one hour in one animal. The mean individual score calculated for 24-48-72 hours was 0.0-0.0-0.0 for erythema and 0.0-0.0-0.0 for edema.

Based on these results, the reaction mass of Stearoylbenzoylmethane and Palmitoylbenzoylmethane is not classified as a skin irritant according to Annex VI of the Directive 67/548/CEE and according to EU Regulation 1272/2008 (CLP).

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 16-FEB-94 to 19-FEB-94
Reliability:
1 (reliable without restriction)
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
not specified
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS:
- Source: Elevage Cunicole de Val de Selle (80160 Prouzel, France)
- Age at study initiation: no data
- Weight at study initiation: 2.8 +- 0.4 kg
- Housing: individually in polystyrene cages (35 x55 x32 cm or 48.2 x 58 x 36.5 cm)
- Diet: 112C pelleted diet (UAR 91360 Villemoisson -sur-Orge,France), ad libitum.
Composition and contaminants analysis performed by the supplier.
- Water: filtered drinking water (0.22 µm), ad libitum; Bacteriological and chemical analysis performed periodically by the C.I.T.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS:
- Temperature: 18 +- 3°C
- Humidity: 30-70 %
- Air changes: no data
- Photoperiod: 12h light-dark cycle

IN-LIFE DATES: from 16-FEB-1994 to 19-FEB-1994
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg of cream coloured powder
- Concentration (if solution): not applicable
Duration of treatment / exposure:
The test substance was instillated into the conjunctival sac of the right eye of each rabbit.
Scoring was performed at 24, 48, 72 hours, then on day 7 and 14 if necessary (presence of ocular lesions)

- Control animals: other: the left eye remained untreated and served as the control
- Removal of test system: no
- Scoring system: according to the Draize scale at 24, 48, 72 hours, then at 7 days as well as 14 days after the instillation if necessary
- Tool used to assess score: to determine the presence or absence of corneal opacity and to evaluate the affected area, 1 or 2 drops of 0.5 % sodium fluorescein solution can be instilled into the eye. In case of difficulty, the eye can be examined under a U.V. lamp.
Observation period (in vivo):
3 days (no ocular lesions observed at 72 hours)
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no
- Time after start of exposure: /


SCORING SYSTEM: according to the Draize scale at 24, 48, 72 hours, then at 7 days as well as 14 days after the instillation if necessary


TOOL USED TO ASSESS SCORE: to determine the presence or absence of corneal opacity and to evaluate the affected area, 1 or 2 drops of 0.5 % sodium fluorescein solution can be instilled into the eye. In case of difficulty, the eye can be examined under a U.V. lamp.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0.57
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Mean individual scores: 1-0-0.7
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0.1
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Mean individual scores: 0.3-0-0

Table 7.3.2/1: 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

Iris

Conjunctivae

Chemosis

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

24 h

0/0/0

0/0/0

2/0/1

1/0/0

48 h

0/0/0

0/0/0

1/0/1

0/0/0

72 h

0/0/0

0/0/0

0/0/0

0/0/0

Average 24h, 48h, 72h

0-0-0

0-0-0

1-0-0.7

0.3-0-0

Reversibility*)

-

-

c.

c.

Average time (unit) for reversion

-

-

72 h.

48 h.

*)Reversibility: c. = completely reversible; = not completely reversible; n. = not reversible

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The reaction mass of Stearoylbenzoylmethane and Palmitoylbenzoylmethane is not classified as eye irritant according to Annex VI of the Directive 67/548/CEE and according to EU Regulation 1272/2008 (CLP).
Executive summary:

Rhodiastab X5 has been tested for acute ocular irritation on 3 New-Zealand White rabbits, according to O.E.C.D. guideline Nb.405 and in compliance with Good Laboratory Practice. The test substance was instilled as supplied in a single dose of0.1 g, into the conjunctival sac of the left eye of the animals. The eyes were not rinsed after the instillation. Ocular examinations were performed 1, 24, 48 and 72 hours after the administration. The mean individual score values were calculated for 24, 48 and 72 hours.

Slight to moderate conjunctival irritation
 (scores of 1 or 2 for chemosis and redness) occurred in all animalsat 1hour. Only one animal still showed chemosis (score 1) and redness (score 2) at 24 hours while the second animal showed only slight redness (score 1) without chemosis and the third didn't show any ocular lesions. Slight redness (score 1) was still observed up to 48 hour in both rabbits.
No iridial lesions or opacity of the cornea were observed. A discharge (score 1 or 2) was noted
at 1hour in all animals, and up to 24 hours in one animal with whitish purulent discharge.

Based on these results, the reaction mass of Stearoylbenzoylmethane and Palmitoylbenzoylmethane is not classified as eye irritant according to Annex VI of the Directive 67/548/CEE and according to EU Regulation 1272/2008 (CLP).

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

Two in vivo studies using rabbits (OECD 404) are available for skin irritation. One study (Clouzeau, 1994) was of reliability 1 according to Klimisch cotation criteria and was therefore selected as the key study. The other study (Mercier, 1988) was of reliability 2 according to Klimisch cotation criteria and was used as a supporting study. In the key study, the test substance was applied as supplied, on a compress moistened with water, in a single dermal dose of 0.5 g, to a 6 cm2clipped area of the right flank skin of 3 male New Zealand White rabbits, during 4 hours under a semi-occlusive dressing. The untreated left flank served as negative control. The cutaneous examinations were performed 1, 24, 48 and 72 hours after removal of the dressing. No edema was noted. Erythema score 1 was observed only at one hour in one animal. The mean individual score calculated for 24-48-72 hours was 0.0-0.0-0.0 for erythema and 0.0-0.0-0.0 for edema.

In the supporting study, the test article was applied in a single dermal dose of 0.5 g, prepared as a paste with 0.23g of sterile Codex liquid paraffin, to a 6 cm2 clipped area of the intact skin of 6 rabbits, during 4 hours under a semi-occlusive dressing. The cutaneous examinations were performed 1, 24, 48 and 72 hours after removal of the dressing.

No edema was noted. Erythema score 1 was observed within a 3-day period in one animal only and at one hour and 24 hours in another animal. The mean score calculated for 24-48-72 hours was0.22for erythema and0.00for edema. Therefore the results of the supporting study are consistent with those of the key studyand support the absence of classification for skin irritation.

Eye irritation:

Two in vivo studies using rabbits (OECD 405) are available for eye irritation. One study (Clouzeau, 1994) was of reliability 1 according to Klimisch cotation criteria and was therefore selected as the key study. The other study (Mercier, 1988) was of reliability 2 according to Klimisch cotation criteria and was used as a supporting study. In the key study, the test substance was instilled as supplied in a single dose of 0.1 g, into the conjunctival sac of the left eye of 3 New-Zealand White rabbits. The eyes were not rinsed after the instillation. Ocular examinations were performed 1, 24, 48 and 72 hours after the administration. The mean individual score values were calculated for 24, 48 and 72 hours. Slight to moderate conjunctival irritation (scores of 1 or 2 for chemosis and redness) occurred in all animals at 1hour. Only one animal still showed chemosis (score 1) and redness (score 2) at 24 hours while the second animal showed only slight redness (score 1) without chemosis and the third didn't show any ocular lesions. Slight redness (score 1) was still observed up to 48 hour in both rabbits. No iridial lesions or opacity of the cornea were observed. A discharge (score 1 or 2) was notedat 1hour in all animals, and up to 24 hours in one animal with whitish purulent discharge.

In the supporting study, the test substance was instilled as supplied in a single dose of 67 mg, into the conjunctival sac of the left eye of 6 New-Zealand White rabbits. Ocular examinations were performed 1, 24, 48 and 72 hours after the administration. The mean individual score values were calculated for 24, 48 and 72 hours. Slight to moderate conjunctival irritation (scores of 1 or 2 for chemosis and redness) occurred in all animals up to 24 hours. Only one animal still showed moderate redness (score 2) at 48 hours while the other animals showed only slight redness and chemosis (score 1) or no redness in one animal. Slight redness (score 1) was still observed up to 72 hour only in two rabbits and slight chemosis in one another animal. Iris congestion (score 1) with circumcorneal injections was observed in all animals at 24 hours, in 4 animals at 48 hours and was minimal only in one animal at 72 hours. No corneal opacity was observed throughout the observation period. These minimal effects still discernible at 72 hours were not considered to represent significant or irreversible irritation. Therefore the results of the supporting study are consistent with those of the key study and support the absence of classification for eye irritation.


Justification for selection of skin irritation / corrosion endpoint:
GLP-compliant study performed according to OECD 404 guideline (Klimish score = 1).

Justification for selection of eye irritation endpoint:
GLP-compliant study performed according to OECD 405 guideline (Klimish score = 1).

Justification for classification or non-classification

The incidence and severity of the signs of irritation observed among the different in vivo rabbit studies were below the criteria of Annex VI Directive 67/548/EEC or EU Regulation 1272/2008 (CLP), therefore warranting no classification for skin or eye irritation.