1,4-Butanediyl 3-(2,4-dimethyl-1,3-dioxolan-2-yl)propanoate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

key study

Study period:

February 21st to March 7th, 2013

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

The reliability of the original study is 1

Justification for type of information:

Justification for Read Across is given in Section 13 of IUCLID.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

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))

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

EPA 712-C-98-192, August 1998.

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nohsan, Notification No. 8147, April 2011; including the most recent partial revisions.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Ethyl 2,4-dimethyl-1,3-dioxolane-2-acetate

EC Number:

228-536-2

EC Name:

Ethyl 2,4-dimethyl-1,3-dioxolane-2-acetate

Cas Number:

6290-17-1

Molecular formula:

C9H16O4

IUPAC Name:

Ethyl (2,4-dimethyl-1,3-dioxolan-2-yl)acetate

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Crl:WI (Han) (outbred, SPF-Quality).

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Females nulliparous and non-pregnant: yes.
- Age at study initiation: young adult animals (approx. 11 weeks old).
- Weight at study initiation: body weight variation did not exceed ± 20 % of the sex mean.
- Health inspection: upon receipt of the animals and prior to dosing. Special attention was paid to the skin to be treated, which was intact and free from any abnormality.
- Housing: individually housed in labeled Makrolon cages (MIII type, height 18 cm.) containing sterilized sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom). During the acclimatization period the animals were group housed in Makrolon cages (MIV type, height 18 cm).
- Diet: free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water: free access to tap water.
- Acclimation period: at least 5 days before start of treatment.

ENVIRONMENTAL CONDITIONS
- Temperature: 18-24 °C.
- Humidity: 40-70 %.
- Air changes: 15 room air changes/hour.
- Photoperiod: 12-hour light/12-hour dark cycle.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Preparation of test site: one day before exposure (Day -1) an area of approximately 5x7 cm on the back of the animal was clipped.
- Application of the test substance: the test substance was applied onto a surgical gauze patch (Surgy 1D). Due to the volatile nature of the test substance, this patch was immediately applied onto to skin.
- % coverage: 10 % of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females.
- Type of wrap if used: a dressing, consisting of a surgical gauze patch (Surgy 1D), successively covered with aluminum foil and Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.

REMOVAL OF TEST SUBSTANCE
- Washing: skin cleaned of residual test substance using tap water.
- Time after start of exposure: 24 hours, after which dressings were removed.

Duration of exposure:

24 hours

Doses:

Single dose of 2000 mg/kg body weight (1.914 ml/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: 15 days.
- Frequency for mortality/viability observations: twice daily.
- Frequency of observations for clinical signs: at periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15. The time of onset, degree and duration were recorded and the symptoms graded according to fixed scales:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1).
- Frequency of weighing: days 1 (pre-administration), 8 and 15.
- Necropsy of survivors performed: at the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Chromodacryorrhoea of the snout was noted for one male and two females on Day 1.

Gross pathology:

Pelvic dilation of the kidney was noted for a single male. This necropsy finding is commonly noted among rats of this age and strain and was therefore considered not toxicologically significant.

Applicant's summary and conclusion

Interpretation of results:

other: not classified as harmful/toxic according to the CLP Regulation (EC) No.1272/2008

Conclusions:

LD50 > 2000 mg/kg bw

Executive summary:

The acute toxicity of the test material after the dermal exposure to rats was evaluated in a limit test according to the OECD Guideline 402 and EU Method B.3. Five male and five female Wistar rats were dermally exposed to a single dose of the substance at 2000 mg/kg bw. The test substance was held in contact with the skin with a dressing, consisting of a surgical gauze patch, successively covered with aluminum foil and Coban elastic bandage. After 24 hours of exposure the dressing was removed and the skin was cleaned from the residual test substance using tap water. The animals were observed for 15 days for mortality, clinical signs, body weight changes and necropsy was conducted after the end of the study.

No mortality was observed. Chromodacryorrhoea of the snout was noted for one male and two females on Day 1 while pelvic dilation of the kidney was noted for a single male. This necropsy finding is commonly noted among rats of this age and strain and was therefore considered not toxicologically significant.

LD50 > 2000 mg/kg bw