2-Oxetanone, 3-C12-16-alkyl-4-C13-17-alkylidene derivs., (4E)-

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

19 August 1998 - 2 September 1998

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study performed according to international guidelines and under GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-Oxetanone, 3-C12-16-alkyl-4-C13-17-alkylidene derivs.

EC Number:

284-932-5

EC Name:

2-Oxetanone, 3-C12-16-alkyl-4-C13-17-alkylidene derivs.

Cas Number:

84989-41-3

Molecular formula:

C28.H52.O2 - C36.H68.O2

IUPAC Name:

(4E)-4-(C13-C17)alkylidene-3-(C12-C16)alkyloxetan-2-one

Details on test material:

Identity: P-2290
Chemical name: 2-Oxetanone, 3-C12-16-alkyI-4-C13-17-alkylidene derivatives
Appearance: Brown waxy liquid
Storage conditions: 4°C in the dark
Batch number: No data
Composition: Alkyl ketene dimer > 85%, Toluene <20ppm
Sample receive: 8 May 1998

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Ltd, Bicester, Oxon, England.
- Age at study initiation: 7-10 weeks
- Weight at study initiation: 212-300g
- Housing: Rats were allocated without conscious bias to cages within the treatment group and housed individually in metal cages with grid floors in Building R14 Room 6. The animals were returned to group housing on Day 3 of the study.
- Diet (e.g. ad libitum): ad libitum, a standard laboratory rodent diet (Special Diet Services RMl(E) SQC expanded pellet).
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 19 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-24.5
- Humidity (%): 39-60
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 19 August 1998 - 2 September 1998

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorso-lumbar region
- % coverage: 10
- Type of wrap if used: The treatment area (approximately 100 mm x 100 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.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of the exposure period the dressings was carefully removed and the treated area of skin was washed with warm water (30 ºC to 40 ºC) to remove any residual test substance. The treated area was blotted dry with absorbent paper.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): of 2.27 ml/kg bodyweight (specific gravity 0.8813).
- Constant volume or concentration used: yes

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Cages of rats were checked at least twice daily for any mortalities. 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 of the clinical signs and time were recorded at each observation. Local dermal irritation at the treatment site was assessed daily.


SCORING SYSTEM:
Erythema and eschar formation:
0 No erythema
1 Very slight erythema (barely perceptible)
2 Well-defined erythema
3 Moderate to severe erythema
4 Severe erythema (beet redness) or eschar formation (injuries in depth) preventing erythema reading

Oedema formation:
0 No oedema
1 Very slight oedema (barely perceptible)
2 Slight oedema (edges of area well-defined by definite raising)
3 Moderate oedema (edges raised approximately 1 millimetre)
4 Severe oedema (raised more than 1 millirnetre and extending beyond the area of exposure)

The bodyweight of each rat was recorded on Days 1 (prior to dosing), 8 and 15. Individual weekly bodyweight changes and group mean bodyweights were calculated.
- Necropsy of survivors performed: yes
- Other examinations performed: All animals were subjected to a macroscopic examination which consisted of opening the abdominal and thoracic cavities. The macroscopic appearance of all tissues was recorded.

Statistics:

None

Results and discussion

Preliminary study:

Not performed

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: No mortalities

Mortality:

There were no deaths following a single dermal application of P-2290 to a group of ten rats (five males and five females) at a dose level of 2000 mg/kg bodyweight

Clinical signs:

other: Slight to well-defined dermal irritation (Grade 1 or 2 erythema, accompanied in one animal by Grade 1 oedema) was seen in two males and one female. These reactions had resolved in all instances by either Day 3 or Day 7. No dermal response to treatment was

Gross pathology:

No abnormalities were recorded at the macroscopic examination on Day 15.

Other findings:

None

Applicant's summary and conclusion

Conclusions:

The acute lethal dermal dose to rats of P-2290 was demonstrated to be greater than 2000 mg/kg bodyweight.

Executive summary:

A study was performed to assess the acute dermal toxicity of P-2290 to the rat. The method followed was that described in: EEC Methods for the determination of toxicity, Annex to Directive 92/69/EEC (OJ No. L383A7 29.12.92), Part B, Method B.3. Acute toxicity (dermal). OECD Guideline for Testing of Chemicals No. 402 "Acute Dermal Toxicity". Adopted: 24 February 1987.

A group of ten rats (five males and five females) received a single topical application of the test substance, administered as supplied at a dose level of 2000 mg/kg bodyweight. All animals were killed and examined macroscopically on Day 15, the end of the observation period. There was no systemic response in any animal throughout the study. Slight to well-defined dermal irritation was noted in three animals, resolving in all instances by Day 7.

No dermal response to treatment was recorded for any other animal throughout the study.A slightly low bodyweight gain was recorded for one female on Day 8, with a similar trend noted for one further female on Day 15. All other animals were considered to have achieved satisfactory bodyweight gains throughout the study. No abnormalities were recorded at the macroscopic examination on Day 15. The acute lethal dermal dose to rats of P-2290 was demonstrated to be greater than 2000 mg/kg bodyweight.