(3-acetyloxy-2,2-dimethylpropyl) acetate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

12 - 28.03.2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

February 24, 1987

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

3-(acetyloxy)-2,2-dimethylpropyl acetate

EC Number:

826-122-1

Cas Number:

13431-57-7

Molecular formula:

C9 H16 O4

IUPAC Name:

3-(acetyloxy)-2,2-dimethylpropyl acetate

Test material form:

liquid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Batch No.of test material: ZH 472 redestilliert.
- Expiration date of the lot/batch: January 2020.

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature. The stability of the test item under storage conditions over the study period was guaranteed by the sponsor, and the sponsor holds this responsibility.
- Homogeneity: The test item was homogeneous by visual inspection.
- Analysis of the test item preparation: Because the test item was used undiluted, no samples were taken.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: none. The test item was applied undiluted.

FORM AS APPLIED IN THE TEST (if different from that of starting material) : undiluted.

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Rat / Wistar / Crl:WI (Han) SPF

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany.
- Females (if applicable) nulliparous and non-pregnant: yes.
- Age at study initiation: Young adult animals (male animals approx. 8 weeks, female animals approx. 12 weeks).
- Weight at study initiation: Animals of comparable weight (± 20% of the mean weight).
- Housing: Single housing in Makrolon cage, type III. Bedding: H 15005-29; Ssniff, Spezialdiäten GmbH (Experimental Animal Diets Inc., 59494 Soest, Germany). Cage enrichment. The animals were housed in fully air-conditioned rooms.
- Diet: VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany, ad libitum.
- Water: Tap water ad libitum.
- Acclimation period: Acclimatization period of at least 5 days before the beginning of the experimental phase; during the acclimatization period, the animals were accustomed to the environmental conditions of the study and to the diet.
- Identification: Individual identification by cage cards and tail marking.
- Reasons for selection of the test species: Rats were selected since this rodent species is recommended in the respective test guidelines. Wistar rats were selected since there is extensive experience available in the laboratory with this strain of rats.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +/- 3°C.
- Humidity (%): 30 – 70% relative humidity.
- Air changes (per hr): Approx. 10.
- Photoperiod (hrs dark / hrs light): 12 h / 12 h (6.00 a.m. – 6.00 p.m. / 6.00 p.m. – 6.00 a.m.).

IN-LIFE DATES: From: 13.03.2018 To: 27.03.2018.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: About 40 cm² covering dorsal and dorsolateral parts of the trunk.
- % coverage: 10% of the body surface.
- Type of wrap if used: semi-occlusive dressing.The test item was covered with an air-permeable dressing (4 layers of absorbent gauze (Ph. Eur. supplied by Lohmann GmbH & Co., KG) and stretch bandage (Fixomull® Stretch (adhesive fleece) supplied by Beiersdorf AG).
- Clipping of the fur: About 24 hours before application.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, rinsing of the application site with warm water.
- Time after start of exposure: 24 hours.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.97 mL/kg bw.
- Concentration (if solution): undiluted.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw / undiluted.

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days.
- Body weight determination: Individual body weights shortly before application (day 0), weekly thereafter and on the last day of observation.
- Clinical observations: Clinical signs for each animal were recorded several times on the day of application and at least once during each workday thereafter.
- Scoring of skin findings: Individual readings 30 – 60 minutes after removal of the semi-occlusive dressing (day 1), weekly thereafter and on the last day of observation.
- Mortality: A check for any dead or moribund animals was made at least once each workday, these records are archived by Bioassay.
- Pathology: Necropsy with gross-pathology examination was performed on the last day of the observation period after sacrifice by CO2-inhalation in a chamber with gradually increasing concentrations.

Assessment of skin reactions:
- The evaluation of skin reactions was performed according to Draize, J. H. "Dermal toxicity." Appraisal of the safety of chemicals in foods, drugs and cosmetics (1959): 46-59. Appraisal of the safety of chemicals in foods, drugs and cosmetics. The association of food and drug officials of the United States Austin, Texas:
- Erythema and eschar formation Grading: 0 - No erythema, 1 - Very slight erythema (barely perceptible), 2 - Well- defined erythema, 3 - Moderate to severe erythema, 4 - Severe erythema (beet redness) to eschar formation preventing grading of erythema.
- Edema formation Grading: 0 - No edema, 1 - Very slight edema (barely perceptible), 2 -Slight edema (edges of area well- defined by definite raising), 3 - Moderate edema (raised approx. 1 mm), 4- Severe edema (raised more than 1 mm and extending beyond area of exposure).
- Descriptions of any dermal findings not covered by this scale were 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: no mortality occured

Mortality:

No mortality occurred.

Clinical signs:

other: No systemic clinical signs were observed during clinical examination.

Gross pathology:

No macroscopic pathologic abnormalities were noted in any animal examined at the end of the study (5 males and 5 females).

Other findings:

No local effects were observed.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study the median lethal dose (LD50) of the test item after dermal application was found to be greater than 2000 mg/kg bw in male and female rats.

Executive summary:

In an acute dermal toxicity study (Limit Test), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of the undiluted test item to the clipped application site (dorsal and dorso-lateral parts of the trunk and covered by semi-occlusive dressing during the 24-hour exposure period. The application area comprised at least 10% of the total body surface). The animals were observed for 14 days.

• No mortality occurred.
• Neither signs of systemic toxicity nor local skin effects were observed in the animals.
• All animals gained weight in a normal range throughout the study period.
• No macroscopic pathologic abnormalities were noted in any animal examined at the end of the study (5 males and 5 females).

Accordingly, the acute dermal median lethal dose (LD50) was determined to be LD50, dermal, rat > 2000 mg/kg bw.