bis(branched-alkyl) 2-{[(1-phenylethyl)amino]methyl}alkanedioate

Skin irritation / corrosion

Some information in this page has been claimed confidential.

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

09 January 2015 to 23 April 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Details on test material:

- Physical state: Pale amber liquid
- Analytical purity: 100 %
- Expiration date of the lot/batch: 08 January 2017
- Storage condition of test material: Approximately 4 °C in the dark

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

ANIMALS AND ANIMAL HUSBANDRY
- Three New Zealand White (Hsdlf:NZW) strain rabbits were supplied by Harlan Laboratories UK Ltd, Leicestershire UK.
- At the start of the study the animals weighed 2.51 to 2.92 kg and were 12 to 20 weeks old.
- After an acclimatisation period of at least 5 days, each animal was given a unique number within the study by writing with black indelible marker-pen on the inner surface of the ear and on the cage label.
- Animals were individually housed in suspended cages.
- Free access to mains drinking water and food (2930C Teklad Global Rabbit diet supplied by Harlan Laboratories Ltd, Oxon, UK) was allowed throughout the study.
- The diet and drinking water were considered not contain any contaminant of a level that might have affected the purpose or integrity of the study.
- Temperature and elative humidity were set to achieve limits of 17 °C to 23 °C and 30 % to 70 % respectively.
- The rate of air exchange was at least 15 changes per hour.
- Lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.
- The animals were provided with environmental enrichment items, which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 mL of the test item

Duration of treatment / exposure:

Four hours

Observation period:

Seven days

Number of animals:

Three

Details on study design:

TEST ITEM FORMULATION
- The absorption of the test item was not determined.

MEASUREMENT OF pH
- The pH of the test item was determined prior to commencement of the study.

PROCEDURE
- On the day before the test, two rabbits were clipped free of fur from the dorsal/flank area using veterinary clippers.
- Only animals with a healthy intact epidermis by gross observation were selected for the study.
- On the day of the test, a suitable test site was selected on the back of each rabbit.
- A quantity (0.5 mL) of the test item was applied directly to the skin under a 2.5 cm x 2.5 cm cotton guaze patch.
- The patch was secured in position with a strip of surgical adhesive tape.
- To prevent the animals interferring with the patches, the trunk of each rabbit was wrapped in an elasticated corset and the animals were returned to their cages for the duration of the exposure period.
- Four hours after application, the corset and patches were removed from each animal and any residual test item removed by gentle swabbing with cotton wool soaked in distilled water.
- Immediately following removal of the patches, and approximately 1, 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored according to defined criteria (see attached scale for evaluation of skin reactions).
- If present, any other skin reactions and clinical signs of toxicity were also recorded.
- Based on the results for the initial two animals, and at the request of the sponsor, a third animal was treated as described previously.
- An additional observation was made on the initial two treated animals on Day 7 to assess the reversibility of skin reactions.
- Individual body weights were recorded on Day 0 (the day of dosing) and at the end of the observation period.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

mean score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: 74911 Male

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

mean score

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 7 d

Remarks on result:

other: 74912 Male

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

mean score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: 74993 Male

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

mean score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: 74911 Male

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

mean score

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible

Remarks:

7 d

Remarks on result:

other: 74912 Male

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

mean score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: 74993 Male

Irritant / corrosive response data:

- Individual scores for erythema/eschar and edema are given in Table 1 (attached).
- Very slight erythema was noted at two treated skin sites immediately and 1 hour after patch removal and at two treated sites at the 24 hour observation.
- Well defined erythema and very slight edema were noted at one treated skin site at the 48 hour and 72 hour observations.
- One treated skin site appeared normal at the 24 hour observation and the other treated skin skite appeared normal at the 7 day observation.
- No evidence of skin irritation was noted at one treated skin site during the study.

Other effects:

BODY WEIGHT
- Individual body weights and body weight change are given in Table 2 (attached).
- All animals showed expected gain in body weight during the study.

Any other information on results incl. tables

MEASUREMENT OF pH

- Test item undiluted as supplied: pH 5

- Aqueous preparation of test item (90 % v/v): pH 5 immediately; pH 10 after 10 minutes; pH 10 after 20 minutes.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test item produced a primary irritation index of 0.7 and was considered to be a mild irritant to rabbit skin according to the Draize scheme. No corrosive effects were noted. The test material is not classified under the terms of Regulation (EC) No 1272/2008.

Executive summary:

GUIDELINE

The irritancy potential of the test item to the skin of the New Zealand White rabbits was investigated using a procedure designed to be compatible with OECD Guideline for the Testing of Chemicals No 404 "Acute Dermal Irritation/Corrosion (adopted 24 April 2002) and Method B.4 Acute Toxicity (Skin Irritation) of Commission Regulation (EC) No 440/2008.

RESULTS

A single 4 hour, semi-occluded, application of the test item to the intact skin of three rabbits produced very slight to well-defined erythema and very slight edema at two treated skin sites. One treated skin site appeared normal at all observations, one other treated skin site appeared normal at the 24 hour observation and the remaining skin site appeared normal at the 7 day observation.

CONCLUSION

The test item produced a primary irritation index of 0.7 and was considered to be a mild irritant to rabbit skin according to the Draize scheme. No corrosive effects were noted.However, the test material is not classified under the terms of Regulation (EC) No 1272/2008 because the mean scores for three animals calculated using data from 24, 48 and 72 hour observations were below the stated limits for erythema and edema.