2-[(2-methyl-1-oxoallyl)oxy]ethyl acetoacetate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

24 November - 15 December 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant study conducted in accordance with international guidelines.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

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:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

Principles of method if other than guideline:

Not applicable.

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Test material form:

other: Colourless to yellowish clear liquid

Details on test material:

- Name of test material (as cited in study report): LZ649
- Physical state: Colourless to yellowish clear liquid
- Expiration date of the lot/batch: 23 November 2014
- Storage condition of test material: Room temperature in the dark, desiccated

Test animals

Species:

rat

Strain:

other: CD (Crl:CD ‘SD’)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: a reputable supplier
- Age at study initiation: eight to twelve weeks
- Weight at study initiation: 335 to 371g for males, and 248 to 274g for females

- Housing: They were housed individually from Day -1 until Day 5 when they were returned to group housing (in groups of five rats of the same sex)., were housed in solid bottomed polycarbonate cages with a stainless steel mesh lid. Each cage contained a quantity of autoclaved wood flake bedding. Cages, food hoppers, water bottles and bedding were changed at appropriate intervals.
- Diet (e.g. ad libitum): free access to a standard rodent diet (Rat and Mouse No. 1 Maintenance Diet), except for overnight prior to and approximately four hours after dosing.
- Water (e.g. ad libitum): Potable water taken from the public supply was freely available via polycarbonate bottles fitted with sipper tubes.
- Acclimation period: 5 days
- During the acclimatisation and study periods, each cage of animals was provided with a soft white untreated chew block for environmental
enrichment.

ENVIRONMENTAL CONDITIONS
- Temperature (°C):19 to 23°C
- Humidity (%):40 to 70%
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): Artificial lighting was controlled to give a cycle of 12 hours continuous light and 12 hours continuous dark per 24 hours.

IN-LIFE DATES: From: 29 September 2011 To: 20 December 2011

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

One day prior to treatment, hair was removed from the dorso-lumbar region of each rat with electric clippers taking care to avoid damaging the skin, exposing an area equivalent to approximately 10% of the total body surface area.
The test substance was applied by spreading it evenly over the prepared skin. The treatment area (approximately 50 mm x 50 mm) was covered with
porous gauze held in place with a non-irritating dressing, and further covered by a waterproof dressing encircled firmly around the trunk of the
animal.
Treatment in this manner was performed on Day 1 (day of dosing) of the study only.
At the end of the 24 hours exposure period the dressing was carefully removed and the treated area of skin was washed with warm water (30 - 40°C), to remove any residual test substance. The treated area was blotted dry with absorbent paper.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bodyweight.

No. of animals per sex per dose:

5 Males and 5 Females.

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: twice daily for any mortalities, the weight of each rat was recorded on Days 1 (prior to dosing), 8 and 15.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other:
Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days, animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only). The nature and severity, where appropriate, of the
clinical signs and the time were recorded at each observation.

Results and discussion

Preliminary study:

No

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths and no systemic response to treatment in any animal.

Clinical signs:

other: No dermal reactions were observed in any animal during the study.

Gross pathology:

No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 15.

Other findings:

No other findings.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute median lethal dermal dose (LD50) to rats of LZ649 was demonstrated to be greater than 2000 mg/kg bodyweight. LZ649 is included in Category 5 or unclassified, according to the Globally Harmonised System (UNITED NATIONS, 2005)

Executive summary:

The acute dermal toxicity study was performed in year 2011 according to OECD Guideline 402 and GLP. There were no deaths and no systemic response to treatment in any animal. No dermal reactions were observed in any animal during the study. No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 15. Therefore, the acute median lethal dermal dose (LD50) to rats of LZ649 was demonstrated to be greater than 2000 mg/kg bodyweight. LZ649 is included in Category 5 or unclassified, according to the Globally Harmonised System (UNITED NATIONS, 2005)