Ethyl 4-oxopiperidine-1-carboxylate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2006-06-28 to 2006-07-07

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Well-documented, GLP-compliant study, performed according to OECD and / or EC guidelines

Data source

Reference

Title:

Unnamed

Year:

2006

Report date:

2006

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

Constituent 1

Reference substance name:

Ethyl 4-oxopiperidine-1-carboxylate

EC Number:

249-984-5

EC Name:

Ethyl 4-oxopiperidine-1-carboxylate

Cas Number:

29976-53-2

Molecular formula:

C8H13NO3

IUPAC Name:

ethyl 4-oxopiperidine-1-carboxylate

Test material form:

liquid

Details on test material:

- Name of test material (as cited in study reports): JNJ-126971-AAA (T000509)
- Physical state: liquid
- Appearance: clear colourless to light yellow liquid

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:young New Zealand White rabbit (SPF), from Harlan Netherlands BV, Kreuzelweg 53, NL-5961 NM Horst, The Netherlands
- Age at study initiation: 11weeks (male), 10-11 weeks (females)
- Weight at study initiation: animal 46: 2323, animal 47: 2041,animal 48: 2114
- Housing: Housed in compliance with AALAC regulations. Standard laboratory conditions, individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks and haysticks 4642 were provided for gnawing.
- Diet (e.g. ad libitum): pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum provided by Provimi Kliba. Results of analysis for contaminants are archived.
- Water (e.g. ad libitum): community tap water from Füllinsdorf, ad libitum. Results of bacteriological, chemical and contaminant analyses are archived.
- Acclimation period: 2006-06-28 to 2006-07-02; under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C):17-23°C
- Humidity (%):30-70%
- Air changes (per hr):10-15 air changes per hour
- Photoperiod (hrs dark / hrs light):12/12. Music was played during the daytime light period

IN-LIFE DATES: From: 2006-07-03 To: 2006-07-07

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5ml
- Concentration (if solution): undiluted

VEHICLE
- Amount(s) applied (volume or weight with unit): not applicable, test item was appplied undiluted

Duration of treatment / exposure:

single dose for 4 hour exposure

Observation period:

-observations: viability/mortality, clinical signs: daily from acclimatization of the animals to the termination of test
-body weights: at start of acclimatization, on the day of application and at termination of observation
-skin reaction: 1, 24, 48 and 72 hours after exposure (remvoal of the dressing, gauze patch and test item.

Number of animals:

3 animals per test (1 male and 2 females)

Details on study design:

TEST SITE
- Area of exposure: left flank; on the day of treatment, 0.5ml of T509 was placed on a surgical gauze patch (ca. 2.5 x 2.5 cm). This gauze patch was applied to the intact skin of the clipped area. The patch was covered with a semi-occlusive dressing.
- % coverage:no data on % (2.5 x 2.5 cm)
- Type of wrap if used: The patch was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): skin was flushed with lukewarm tap water to clean the application site so that any reactions were clearly visible at that time.
- Time after start of exposure: 4hours

SCORING SYSTEM: the skin reaction was assessed according to the numerical scoring system listed in the Commission directive 2004/73/EC, April 29, 2004. The skin reaction was assessed at approximately 1, 24, 48 and 72 hours after exposure (removal of the dressing, gauze patch and test item). If evident, corrosive or staining properties of the test item were described and recorded.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Remarks:

mean

Basis:

animal:

Remarks:

46

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: clipped skin

Results 2

Irritation parameter:

erythema score

Remarks:

mean

Basis:

animal:

Remarks:

47

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: clipped skin

Results 3

Irritation parameter:

erythema score

Remarks:

mean

Basis:

animal:

Remarks:

48

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: clipped skin

Results 4

Irritation parameter:

edema score

Remarks:

mean

Basis:

animal:

Remarks:

46

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: clipped skin

Results 5

Irritation parameter:

edema score

Remarks:

mean

Basis:

animal:

Remarks:

47

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: clipped skin

Results 6

Irritation parameter:

edema score

Remarks:

mean

Basis:

animal:

Remarks:

48

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: clipped skin

Irritant / corrosive response data:

The test item did not elicit any skin reactions at the application site of any animal at any of the observation times (all scores 0). The individual mean score for erythema/eschar and oedema for each of the three animals was therefore 0. The test item caused no staining of the treated skin. No corrosive effects were noted on the treated skin of any animal at any of the measuring intervals and no clinical signs were observed.

Other effects:

No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred. The body weights of all rabbits were considered to be within the normal range of variability

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based upon the referred classification criteria (Commission Directive 2001/59/EC of August 2001), T509 is considered to be not irritating to rabbit skin.