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Administrative data

Description of key information

Not corrosive or irritating. Value used for CSA is taken from the 2000 study as explained in DNEL derivation.

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:
25th July - 7th August 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River UK Ltd, Margate, Kent, England.
- Age at study initiation: Approximately 15 weeks of age (prior to treatment (Day 1)).
- Weight at study initiation: 3.3 to 3.6 kg.
- Housing: Individually in plastic cages with perforated floors.
- Diet (e.g. ad libitum): SDS Stanrab (P) Rabbit Diet ad libitum
- Water (e.g. ad libitum): Drinking water ad libitum
- Acclimation period: All rabbit were acclimatised to the experimental environment.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 (approximately)
- Humidity (%): 30 - 70 (relative humidity)
- Air changes (per hr): 19 (approximately)
- Photoperiod (hrs dark / hrs light): 12 hours of artificial light (0700 - 1900 hours) in each 24 hours period.

IN-LIFE DATES: From: 25 July 1995 To: 7 August 1995.
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
4 hours
Observation period:
- Environmental parameters: Recorded daily.
- Clinical signs: All animals were observed daily for signs of ill health or toxicity.
- Dermal responses: Examination of the treated skin was made on Day 1 (i.e. approximately 60 minutes after removal of the dressings) and on Days 2, 3 and 4 (equivalent to 24, 48 and 72 hours after exposure). Additional observations were made on Days 5 to 14.
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 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 100 mm x 100 mm. A 0.5 ml amount of the test substance was applied under a 25 mm x 25 mm gauze pad to one intact skin site on each animal.

- Type of wrap if used: Each treatment site was covered with “Elastoplast” elastic adhesive dressing for four hours.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of the exposure period, the semi-occlusive dressing and gauze pad were removed and the treatment site was washed with warm water (30° to 40°C) to remove any residual test substance. The treated area was blotted dry with absorbent paper.
- Time after start of exposure: 4 hours

SCORING SYSTEM: Local dermal irritation was assessed using the prescribed numerical system in the attached report. Any other lesion not covered by this scoring system, was described.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3.3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Necrosis.
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3.3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Necrosis.
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3.3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Necrosis.
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Edges of necrotic area lifting.
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.3
Max. score:
2
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Edges of necrotic area lifting.
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.3
Max. score:
2
Reversibility:
not fully reversible within: 14 days.
Remarks on result:
other: Edges of necrotic area lifting.
Irritant / corrosive response data:
- Dermal responses: The numerical values given to the dermal reactions elicited by New Eporva 800 are shown in Table 1 of the attached report. Well-defined dermal reactions were seen following removal of bandages. Severe dermal irritation with necrosis developed in all these animals on Day 2 and persisted throughout the observation period to Day 14 (day of termination).
Other effects:
- Clinical signs: There were no signs of toxicity or ill health in any rabbit during the observation period.
Table 1. Dermal reactions observed after application of New Eporva 800

Rabbit number and sex
E = Erythema
O = Oedema
Day
1*
2
3
4
5
6
7
8
9
10
11
12
13
14
1250
E
a2
b4
b4
b4
b4
b4
b4
b4
b4
b4
b4
b4
b4
b4
O
2
2
2
1
1
1
1
c1
c1

c1

c1

c1

c1

c1

1251
E
a2
b4
b4
b4
b4
b4
b4
b4
b4
b4
b4
b4
b4
b4
O
2
1
1
1
1
1
1
c1
c1

c1

c1

c1

c1

c1

1259
E
a2
b4
b4
b4
b4
b4
b4
b4
b4
b4
b4
b4
b4
b4
O
2
1
1
1
1
1
1
1
c1

c1

c1

c1

c1

c1

 
* Approximately 60 minutes after removal of the dressing
a Brown staining from dose; b Necrosis; c Edges of necrotic area lifting
Interpretation of results:
Category 1B (corrosive) based on GHS criteria
Conclusions:
A single semi-occlusive application of New Eporva 800 to intact rabbit skin for four hours elicited severe persistent dermal irritation. The necrosis, severe erythema and the persistence until day 14 of the study after a 4 hour exposure period warrant a classification as category 1B (H314 causes severe burns and eye damage).
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because the substance is a strong acid (pH <= 2.0) or base (pH => 11.5) and the available information indicates that it should be classified as serious eye damage (Category 1)
Endpoint conclusion
Endpoint conclusion:
no study available

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The 1995 study (OECD 404) was classified a key study based on its rationale for reliability (Klimisch 1, reliable without restriction). As severe persistent dermal irritation with necrosis and severe erythema persisting until day 14 was observed, Epofloc L-1R warranted classification as category 1C (H314 causes severe burns and eye damage). The 2000 study of the same guideline was also classified a key study (Klimisch 1). In this study, Epofloc L-1R caused only very slight to well-defined dermal irritation, and did not meet the classification criteria for skin corrosion or irritation in accordance with Guidance to Regulation (EC) No 1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures, Version 4.0, November 2013. Although both are key studies, the 2000 study is the pertinent study following minor test material changes between tests, a result of the manufacturing process being optimized in 1995 and 2000. The current batch used in the 2000 study and thereafter has been confirmed as that currently used in the EU. Furthermore, data from two supporting in vitro studies performed in 2014 using the reconstituted, human epidermal 3D-skin model (Klimisch 3, not reliable), and skin corrosion test (OECD 431) (Klimisch 2, reliable with restrictions) both confirmed Epofloc L-1R was not a skin irritant or caused a skin corrosive effect. This substance has a pH of 12.1, therefore, on grounds of animal welfare, no eye irritation studies will be undertaken.


Justification for selection of skin irritation / corrosion endpoint:
The 1995 study (OECD 404) was classified a key study based on its rationale for reliability (Klimisch 1, reliable without restriction). As severe persistent dermal irritation with necrosis and severe erythema persisting until day 14 was observed, Epofloc L-1R warranted classification as category 1C (H314 causes severe burns and eye damage). The 2000 study of the same guideline was also classified a key study (Klimisch 1). In this study, Epofloc L-1R caused only very slight to well-defined dermal irritation, and did not meet the classification criteria for skin corrosion or irritation in accordance with Guidance to Regulation (EC) No 1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures, Version 4.0, November 2013. Although both are key studies, the 2000 study is the pertinent study following minor test material changes between tests, a result of the manufacturing process being optimized in 1995 and 2000. The current batch used in the 2000 study and thereafter has been confirmed as that currently used in the EU. Furthermore, data from two supporting in vitro studies performed in 2014 using the reconstituted, human epidermal 3D-skin model (Klimisch 3, not reliable), and skin corrosion test (OECD 431) (Klimisch 2, reliable with restrictions) both confirmed Epofloc L-1R was not a skin irritant or caused a skin corrosive effect.

Effects on skin irritation/corrosion: corrosive

Justification for classification or non-classification

This substance was classified as Corrosive 1C, H314: Causes severe skin burns and eye damage. However this classification does not stand for the substance now supplied but a risk assessment has been completed. If this classification did apply it would not lead to significant risk.