Benzoic acid, 2-ethoxy-5-[(4-methyl-1-piperazinyl)sulfonyl]-, ethyl ester

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 2017-02-03 to 2017-02-20

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

2015

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

May 2008

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

ethyl 2-ethoxy-5-[(4-methylpiperazin-1-yl)sulfonyl]benzoate

EC Number:

814-360-9

Cas Number:

304435-84-5

Molecular formula:

C16H24N2O5S

IUPAC Name:

ethyl 2-ethoxy-5-[(4-methylpiperazin-1-yl)sulfonyl]benzoate

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

Batch No.: APM0005851606003
Purity/Composition: 99.8% w/w
Test item storage: At room temperature

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River France, L’Arbresle
- Age at study initiation: approximately 28-29 weeks old
- Weight at study initiation: 4069 to 4086 g
- Housing: On arrival and following assignment to the study, animals were housed individually in labeled cages with perforated floors (Ebeco, Germany, dimensions 67 x 62 x 55 cm) equipped with water bottles.
- Diet (e.g. ad libitum): Pelleted diet for rabbits provided once daily throughout the study
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18°C to 24°C
- Humidity (%): 40% to 70%
- Air changes (per hr): Ten or greater
- Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark cycle

IN-LIFE DATES: From: 2017-02-03 To: 2017-02-20

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 grams

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.4 mL

Duration of treatment / exposure:

4 hours

Observation period:

14 days

Number of animals:

3 Males

Details on study design:

TEST SITE
- Area of exposure: 2x3 cm
- Type of wrap if used: Coban elastic bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the skin cleaned of residual test item using tap water
- Time after start of exposure: Four hours

OBSERVATION TIME POINTS
- Mortality/Moribundity Checks: twice daily, once in the morning and once in the afternoon
- Clinical Observations: once daily
- Body Weights: on Day 1 (predose) and on the day of the final observation.
- Irritation: assessed at approximately 1, 24, 48 and 72 hours after the removal of the dressings and test item.

SCORING SYSTEM:
- Method of calculation: Draize

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: Mean of 24, 48 and 72 hours

Score:

0

Max. score:

0

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

other: Mean of 24, 48 and 72 hours

Score:

0

Max. score:

0

Irritant / corrosive response data:

- Irritation: No skin irritation was caused by 4 hours exposure to test substance.
- Corrosion: There was no evidence of a corrosive effect on the skin.

Other effects:

- Coloration / Remnants: No staining of the treated skin by the test item was observed and no test item remnants were seen.
- Toxicity / Mortality: No signs of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Any other information on results incl. tables

Individual skin irritation scores:

Animal	227		218		222
Time after exposure	Erythema (0-4)	Oedema (0-4)	Erythema (0-4)	Oedema (0-4)	Erythema (0-4)	Oedema (0-4)
1 hour	0	0	0	0	0	0
24 hours	0	0	0	0	0	0
48 hours	0	0	0	0	0	0
72 hours	0	0	0	0	0	0

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on these results the test substance does not have to be classified and has no obligatory labelling requirement for skin irritation according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).

Executive summary:

The objective of this primary skin irritation study was to assess the possible irritation or corrosion potential of a single dose of test subbstance when administered to the intact skin of rabbits according to OECD 404.

Three rabbits were exposed to 0.5 grams of test substance, moistened with water by application onto clipped skin for 4 hours using a semi-occlusive dressing. Skin reactions were assessed 1, 24, 48 and 72 hours after exposure.

No skin irritation was caused by 4 hours exposure to test substance.

Based on these results the test substance does not have to be classified and has no obligatory labelling requirement for skin irritation according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).