Reaction products of 1,4-Benzenedimethanol and 1-naphthol

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

16 October 2012 to 19 October 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

In-Vivo study carried out as substance is intended for global registration where In-Vivo data is required.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

See any other information section for details

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

See any other information section for details

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

yes

Remarks:

See any other information section for details

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Reaction products of 1,4-Benzenedimethanol and 1-naphthol

EC Number:

834-894-6

Cas Number:

113601-85-7

Molecular formula:

C10H8O to C82H64O5

IUPAC Name:

Reaction products of 1,4-Benzenedimethanol and 1-naphthol

Test material form:

solid

Details on test material:

Name: CAS 113601-85-7
Chemical name: 1,4-Benzenedimethanol, polymer with 1-naphthalenol
Batch/Lot number: 0950986
Description: Brown, solid
Purity: 100%
Expiry date: 08 February 2020
Storage conditions: Controlled room temperature (15-25°C ≤ 70% relative humidity)
Safety precautions: Routine safety precautions (gloves, goggles, face mask, lab coat) for unknown materials were applied to ensure personnel health and safety. Causes skin irritation and serious eye irritation.

Specific details on test material used for the study:

No further details specified in the study report

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

EXPERIMENTAL ANIMALS
Species and strain: New Zealand White rabbits
Source: S&K-LAP Kft.
2173 Kartal, Császár út 135, HUNGARY
Justification of strain: The New Zealand White albino rabbit is one of the standard strains used for acute irritation toxicity studies.
Animal health: Only animals in acceptable health condition were used for the test.
Number of animals: 3
Age of animals at treatment: ~14 - 15 weeks old
Sex: Male
Body weight range at the
beginning of the in-life phase: 3477 – 3618 g
end of the in-life phase: 3572 – 3701 g
Acclimation time: 33 days
Animal identification: The animals were identified by engraved ear tags. The cages were marked with individual identity cards with information about study code, sex, cage number, dose group and individual animal number.

Husbandry
Number of animal room: 618
Lighting periods: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature range during
the study: 18.5-22.2 °C
Relative humidity during
the study: 38 – 82 %
Housing/Enrichment: 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.

Ventilation: 15-20 air exchanges/hour
The temperature and relative humidity values were measured continuously. The measured range was checked at least daily during the acclimatisation and experimental phases.
Variation from the target relative humidity (max. 82 %) was observed during the acclimation period. These deviations were considered to have no impact on the animal health, as certified by the Clinical Veterinarian, or on the outcome of the study and interpretation of the results.

Food and Feeding
Animals received UNI diet for rabbits produced by AGRIBRANDS Europe Hungary PLC, H-5300 Karcag, Madarasi út, Hungary, ad libitum. Animals were provided with the following batch:
• 0140 07 12, expiry date: 25 October 2012
The details of the diet used will be archived with the raw data and are not reported.

Water Supply
The animals received municipal tap water, as for human consumption, ad libitum, from an automatic system.

Water Analysis
The drinking water is routinely analysed and is considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study. The quality control analysis is performed once every three months and microbiological assessment is performed monthly by Veszprém County Institute of State Public Health and Medical Officer Service (ÁNTSZ, H-8201 Veszprém, József A.u.36., Hungary). Copies of the relevant Certificates of Analysis are retained in the archives at CiToxLAB Hungary Ltd.

Test system

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

The test item was used as supplied, as a single dose of 0.5 g, applied to the test area.

Duration of treatment / exposure:

4 hours

Observation period:

To assess skin irritation, animals were examined at 1, 24, 48, and 72 hours after the patch removal. Additional general examinations were performed daily.

Number of animals:

3

Details on study design:

TREATMENT PERIOD
Day of treatment
Day 0
16 October 2012

Animal skin examination and assignment to study
Day 0 (pre-treatment)
16 October 2012

Body weight measurement
Day 0, 3
16 and 19 October 2012

Clinical observation
Scoring at 1, 24, 48 and 72 hours after treatment
(16, 17, 18 and 19 October 2012)

End of in life phase
Day 3
19 October 2012

ADMINISTRATION OF THE TEST ITEM

Dosage
The test item was used as supplied, as a single dose of 0.5 g, applied to the test area. The untreated skin of each animal served as a control. The test item was powdered which was dispensed for studies with this test item.

Application of the Test Item
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 and flanks 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) of approximately 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. Three minutes and 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.

Duration of Exposure
Duration of exposure: 4 hours. After the treatment period, the test item was removed with water at body temperature.

OBSERVATIONS AND SCORING

Clinical Observations
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.

Scoring and Assessment of Local Reactions
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

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Other effects:

Measurement of Body Weight
Body weights were recorded at the beginning and at the end of experiment.

Termination
At the end of the observation period, euthanasia of the animal was by intramuscular injections of CP-Ketamin 10 % and CP-Xylazin 2 % followed by i.v. Euthasol® 40% anaesthesia (see details in 3.1.2.). Death was verified by checking pupil and cornea reflex, absence of respiration and pulse.

Any other information on results incl. tables

SCORING OF ERYTHEMA FORMATION

 

Animal No./ Sex	Body weight (g)		1 h	24 h	48 h	72 h
	At the beginning of the study	At the end of the study
2607 / M	3618	3701	0	0	0	0
2643 / M	3477	3572	0	0	0	0
2606 / M	3552	3644	0	0	0	0
Total	-	-	0	0	0	0

 

M = male

h = hour

 

SCORING OF OEDEMA FORMATION

Animal No./ Sex	Body weight (g)		1 h	24 h	48 h	72 h
	At the beginning of the study	At the end of the study
2607 / M	3618	3701	1	0	0	0
2643 / M	3477	3572	0	0	0	0
2606 / M	3552	3644	0	0	0	0
Total	-	-	1	0	0	0

 

M = male

h = hour

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Conclusions:

SN-475N does not require classification as a skin irritant.

Executive summary:

An acute skin irritation study was performed with SN-475N in 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, 2002).

A volume of 0.5 g 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.

At observation one hour after patch removal, oedema (score 1) on 1/3 animals were observed on the skin of the treated animals.

At observation 24, 48 and 72 hours after patch removal, there were no observed clinical signs noted on the skin of the treated animals.

As no clinical signs were observed at 72 hours after patch removal, the study was terminated after the 72 hours observation.

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 Directive 2001/59/EC, SN-475N does not require classification as a skin irritant.

According to the UN Globally Harmonised System of Classification and Labelling of Chemicals, SN-475N does not require classification as a skin irritant.

According to the classification system based on the scheme devised by Draize (1959), SN-475N is a "non-irritant"