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Acute Toxicity: dermal

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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 guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
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

Constituent 1
Chemical structure
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:
There were no signs of systemic toxicity.
Body weight:
All animals showed expected gains in bodyweight over the study period. Individual body weights can be seen in Table 2.
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:
Migrated information 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.

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