2-phenoxyethyl isobutyrate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

18 June 2012 to 11 July 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to valid guidelines and the study was conducted under GLP conditions.

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:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-phenoxyethyl isobutyrate

EC Number:

203-127-1

EC Name:

2-phenoxyethyl isobutyrate

Cas Number:

103-60-6

Molecular formula:

C12H16O3

IUPAC Name:

2-phenoxyethyl 2-methylpropanoate

Test material form:

other: liquid (undefined)

Details on test material:

- Name of test material (as cited in study report): 2-phenoxyethyl isobutyrate.
- Physical state: Clear colourless liquid.
- Storage condition of test material: room temperature in the dark.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 8 - 12 weeks.
- Weight at study initiation: At least 200 g.
- Housing: Individually during exposure period and in groups of up to four, by sex, for the remainder of the study.
- Diet: Rodent diet ad libitum.
- Water: Mains drinking water, ad libitum.
- Acclimation period: at least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25 ºC
- Humidity (%): 30 - 70 %
- Air changes (per hr): at least 15 changes per hour.
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Backs and flanks of each animal, prepared by clipping free of hair the day before exposure.
- % coverage: Approximately 10% of the total body surface area.
- Type of wrap if used: A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: After the 24 hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with arachis oil BP to remove any residual test material.
- Time after start of exposure: 24 hours after exposure.

TEST MATERIAL
- Amount applied: 1.93 mL/kg

TEST PROCEDURE
- Initially one male and one female were tested to assess the toxicity of the test material. Animals were dosed in the same manner as the other test animals. No mortalities were observed so the remaining animals were dosed. The results were combined for evaluation.

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 males and 5 females.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for deaths or overt signs of toxicity 0.5, 1, 2 and 4 hours after dosing and once daily thereafter for 14 days. Individual bodyweights were recorded prior to application of the test material on day 0 and on days 7 and 14.
- Necropsy of survivors performed: Yes (external examination and opening the abdomen and thoracic cavities to check for any macroscopic abnormalities).
- Other examinations performed: Following removal of the test material the test sites were examined for evidence of primary skin irritation and scored according to Draize (1977) (See "Any other information on materials and methods"), any other skin reactions, if present were also recorded.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: There were no deaths and no signs of overt toxicity.

Mortality:

There were no deaths.

Clinical signs:

other: There were no signs of systemic toxicity.

Gross pathology:

A cavity was noted in the right kidney of one male but this was considered to be a genetic defect and not related to treatment with the test material. No abnormalities were noted at necropsy of the remaining animals.

Other findings:

Dermal irritation: There were no signs of dermal irritation.

Any other information on results incl. tables

Table 2: Individual Bodyweights

Dose Level mg/kg	Animal Number and Sex	Bodyweight (g) at Day			Bodyweight Change (g) During Week)
		0	7	14	1	2
2000	1-0 Male	275	294	316	19	22
	3-0 Male *	242	272	312	30	40
	3-1 Male	236	272	310	36	38
	3-2 Male	247	277	308	30	31
	3-3 Male	242	277	313	35	36
	2-0 Female	206	210	215	4	5
	4-0 Female	215	225	232	10	7
	4-1 Female	218	220	228	2	8
	4-2 Female	218	227	230	9	3
	4-3 Female	208	219	226	11	7

*Individual with the cavity in the right kidney.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the study, the acute dermal LD50 was determined to be greater than 2000 mg/kg bw.

Executive summary:

The acute dermal toxicity of the test material was determined in a study conducted in compliance with standardised guidelines OECD 402 and EU Method B.3. During the study, two animals (one male and one female) were given a single, 24 -hour semi-occluded dermal application of the undiluted test material to intact skin at a dose level of 2000 mg/kg bw. Based on the results of the initial test, a further group of four males and four females was similarly treated. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Under the conditions of the study, there were no deaths or overt signs of systemic toxicity. There were no signs of dermal irritation and all animals showed expected gains in bodyweight over the study period. At necropsy a cavity was noted in the right kidney of one male but this was considered to be a genetic defect and not related to treatment with the test material. No abnormalities were noted at necropsy of the remaining animals. In consideration of these findings the LD50 was determined to be greater than 2000 mg/kg bw.