oligomeric reaction product of 2-hydroxybenzaldehyde with 1-chloro-2,3-epoxypropane and phenol

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10 November 2015 - 16 November 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

In vitro skin corrosivity and irritation studies were performed prior to treatment on any animals. Based on the results from the In Vitro Skin Corrosivity Test
(CiToxLAB code: 15/289-039B) in the EPISKIN model test and In Vitro Skin Irritation Test in the EPISKIN Model (CiToxLAB code: 15/289-043B) with EPICLON EXA-7250 concluded that the test item is not corrosive or irritant to the skin. It was concluded that an in vivo study is required for proper classification.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

These deviations are considered to have no impact on the outcome of the study and interpretation of the results.

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

2-({2-[bis({2-[(oxiran-2-yl)methoxy]phenyl})methyl]phenoxy}methyl)oxirane; 2-({2-[bis({4-[(oxiran-2-yl)methoxy]phenyl})methyl]phenoxy}methyl)oxirane; 2-{[2-({2-[(oxiran-2-yl)methoxy]phenyl}({4-[(oxiran-2-yl)methoxy]phenyl})methyl)phenoxy]methyl}oxirane

EC Number:

942-639-6

IUPAC Name:

2-({2-[bis({2-[(oxiran-2-yl)methoxy]phenyl})methyl]phenoxy}methyl)oxirane; 2-({2-[bis({4-[(oxiran-2-yl)methoxy]phenyl})methyl]phenoxy}methyl)oxirane; 2-{[2-({2-[(oxiran-2-yl)methoxy]phenyl}({4-[(oxiran-2-yl)methoxy]phenyl})methyl)phenoxy]methyl}oxirane

Test material form:

solid

Details on test material:

Name: EPICLON EXA-7250
Batch/Lot number: B006
Appearance: Brown solid (in smaller amount colour is yellow)
Purity: >99%
Manufacture date: 02 October 2014
Expiry date: 02 March 2017
Storage condition: Room temperature 15-25°C, below 70 RH%
Safety precautions: Routine safety precautions (lab coat, gloves, safety glasses, face
mask) for unknown materials were applied to assure personnel
health and safety.

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material:B006
- Expiration date of the lot/batch:02 March 2017

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Controlled room temperature 15-25°C, below 70 RH%

FORM AS APPLIED IN THE TEST: yes

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: S&K-LAP Kft. 2173 Kartal, Császár út 135, HUNGARY
- Age at study initiation: 18 weeks old
- Weight at study initiation: 3316 – 3825 g
- Housing:Rabbits were individually housed in AAALAC approved metal wire rabbit cages. Cages were of an open wire structure and cages were placed together to allow some social interaction with rabbit(s) in adjoining cages.
- Diet (e.g. ad libitum): Animals received UNI diet for rabbits produced by Cargill Takarmány Zrt., H- 5300 Karcag, Madarasi út, Hungary, ad libitum.
- Water (e.g. ad libitum): The animals received municipal tap water, as for human consumption, ad libitum, from an automatic system.
- Acclimation period:51 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.0 – 23.2 °C
- Humidity (%): 25 – 64 %
- Air changes (per hr): 15-20 air exchanges/hour
- Photoperiod (hrs dark / hrs light):12 hours daily, from 6.00 a.m. to 6.00 p.m.

IN-LIFE DATES: From: 21 September 2015 To: 16 November 2015

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: The untreated skin of each animal served as a control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): The test item was administered as a single dose of 0.5 g, applied to the test area.

Duration of treatment / exposure:

4 hours.

Observation period:

Animals were examined for signs of erythema and oedema, and the responses scored at 60 minutes and then at 24, 48 and 72 hours after patch removal.

Number of animals:

3 rabbits

Details on study design:

TEST SITE
Patch testing was used to detect primary irritating effects of the test item. Three male animals in acceptable health condition were selected for this test. Approximately 24 hours prior to the test, the hair was clipped from the back of the animals. Removal of hair was performed in two steps. The majority of hair
was clipped with an electronic hair clipper and the remaining hair was moistened with water and shaved with a razor. The test item was applied to an approximately 6 cm² area of intact skin as follows:

• A single layer of a fine medical gauze (open-weave with large holes) ofapproximately 5x5 cm was placed over the application area,
• The appropriate amount of test item was carefully spread over the application area (the gauze helped maintain the test item in place),
• Three more layers of gauze were placed over the test item,
• These gauze patches were kept in contact with the skin by a patch of clear plastic with a surrounding adhesive hypoallergenic plaster to ensure continued good contact between the moistened test item and the shaved skin.
• The entire trunks of the animals were wrapped with plastic wrap for 4 hours.
• Medical elastic tubing was placed over the plastic to keep it in place. An initial test was performed using one animal. One hour after application of the
test item, the application site was examined. No severe irritation or corrosive effect was found in the initial test, therefore the bandage was replaced and the
exposure continued for a further 3 hours (a total 4 hours exposure). Two additional animals were then included in the study.

REMOVAL OF TEST SUBSTANCE
Since the test item had adhesive properties it could not be executed. Any expressive force could have cause the damage of the skin, thus the test item was left on the skin until the termination time.

OBSERVATION TIME POINTS
60 minutes and then at 24, 48 and 72 hours after patch removal.

SCORING SYSTEM:
- Method of calculation: The dermal irritation scores were evaluated according to the scoring system by Draize (1959) shown in Appendix 1. The animals were observed for 72 hours and the duration of the study was sufficient to evaluate fully the reversibility or irreversibility of the effects observed.

Results and discussion

In vivo

Results

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

24/48/72 h

Score:

0

Irritant / corrosive response data:

MORTALITY
There was no mortality observed during the study.
BODY WEIGHTS
There was no test item related effect on body weight.
CLINICAL OBSERVATION
General Daily Examination
There were no test item related clinical signs noted.

Examination of Skin-Irritancy
At observation 1, 24, 48 and 72 hours after patch removal, there were no adverse signs noted on the skin of the treated animals; however the test item
adhered to the skin and could not be removed after 4 hours. Any expressive force could have cause damage of the skin thus it was decided to leave the test item on the skin. The test item did not disturb the observation of clinical signs. At 72 hours after patch removal, remaining test item was still present on the skin and there were no adverse signs noted. The termination of the experiment was executed on the 6th day after a discussion and confirmation of the Sponsor.
The animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for erythema were 0.00, 0.00 and 0.00 respectively.
The animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for oedema were 0.00, 0.00 and 0.00 respectively.
The Primary Irritation Index (considering readings at 24, 48 and 72 hours after patch removal) was calculated as 0.00.

Any other information on results incl. tables

Results were presented and interpreted according to (I) Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labelling and packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 1999/45/EC, and amending Regulation (EC) No 1907/2006 and the (II) UN Globally Harmonised System of Classification and Labelling of Chemicals.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

According to the UN Globally Harmonised System of Classification and Labelling of Chemicals, EPICLON EXA-7250 does not require classification as a skin irritant. According to the classification system based on the scheme devised by Draize (1959), EPICLON EXA-7250 is a "non-irritant".

Executive summary:

An acute skin irritation study was performed with EPICLON EXA-7250 in three New Zealand White rabbits. Parameters monitored during this study included mortality, body weight measurements and clinical observations. The irritancy of the test item was evaluated according to the Draize method (OECD No.: 404, 2015).

A weight of 0.5 g of test item was applied to the skin of the experimental animals. The test item was applied as a single dose. Sufficient water to damp the material was used to ensure good contact with the skin. Sterile gauze pads were placed on the skin of rabbits. These gauze pads were kept in contact with the skin by a patch with a surrounding adhesive hypoallergenic plaster. The trunk was wrapped in clear plastic with medical tubing used to hold the patch in place. The untreated skin of each animal served as control.

After 4 hours, the remaining test item was removed with water at body temperature. To assess skin irritation, animals were examined at 1, 24, 48, and 72 hours after the patch removal. Additional general examinations were performed daily.

There was no mortality during the observation period. There was no test item related effect on body weight. The test item adhered to the skin during the whole experiment and could not be removed, however this did not disturbed the observation and at observation 1, 24, 48, 72 hours after patch removal, there were no observed adverse effect noted on the skin of the treated animals. Since the test adhered to the skin the experiment was terminated only after discussion with the sponsor on the 6th day. The animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for erythema were 0.00, 0.00 and 0.00 respectively. The animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for oedema were 0.00, 0.00 and 0.00 respectively.

The Primary Irritation Index (considering readings at 24, 48 and 72 hours after patch removal) was calculated as 0.00.

According to the UN Globally Harmonised System of Classification and Labelling of Chemicals, EPICLON EXA-7250 does not require classification as a skin irritant. According to the classification system based on the scheme devised by Draize (1959), EPICLON EXA-7250 is a "non-irritant".