Diisodecyl sebacate

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:

01 to 15-July-2010

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study on a read-across compound has been performed according to OECD and EC guidelines and according to GLP principles.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

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

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000; including the most recent partial revisions.

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:

Diisodecyl adipate

EC Number:

248-299-9

EC Name:

Diisodecyl adipate

Cas Number:

27178-16-1

Molecular formula:

C26H50O4

IUPAC Name:

bis(8-methylnonyl) adipate

Test material form:

other: Clear colourless oily liquid

Details on test material:

- Name of test material (as cited in study report): Diisodecyl adipate
- Molecular formula (if other than submission substance): C26-H50-O4
- Molecular weight (if other than submission substance): 426.677
- Smiles notation (if other than submission substance): C(CCCCC(OCCCCCCCC(C)C)=O)(OCCCCCCCC(C)C)=O
- InChl (if other than submission substance): InChI=1S/C26H50O4/c1-23(2)17-11-7-5-9-15-21-29-25(27)19-13-14-20-26(28)30-22-16-10-6-8-12-18-24(3)4/h23-24H,5-22H2,1-4H3
- Structural formula attached as image file (if other than submission substance): see Fig. 1
- Substance type:Clear colourless oily liquid
- Physical state: liquid
- Analytical purity: 99.7% (based on GC-FID area-%)
- Lot/batch No.: D30204
- Expiration date of the lot/batch: 25 January 2013
- Stability under storage conditions: Stable
- Storage condition of test material: At room temperature in the dark
- pH (1% in water, indicative range): 7.3 – 7.4
-Specific Gravity: 0.92

Test animals

Species:

rat

Strain:

other: Wistar strain, Crl:WI (Han)

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: Young adult animals (approx.11 weeks old)
- Weight at study initiation: Body weight variation was within +/- 20% of the sex mean.
- Housing: Individually housed in labeled Macrolon cages (MIII type, height 18 cm.) containing sterilized sawdust as bedding material (Woody-Clean type 3/4, Tecnilab-BMI BV, Someren, The Netherlands) and paper as cage-enrichment (Enviro-dri, Tecnilab-BMI BV, Someren, The Netherlands).
- Diet (e.g. ad libitum): Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: The acclimatization period was at least 5 days before the start of treatment under laboratory conditions.
- Health inspection: A health inspection was performed prior to treatment, to ensure that the animals were in a good state of health. Special attention was paid to the skin to be treated, which was intact and free from any abnormality.

Results of analysis for diet (nutrients and contaminants), sawdust, paper and water were assessed and did not reveal any findings that were considered to have affected the study integrity. All certificates and results of analysis are retained in the NOTOX archives.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.0 – 21.6ºC
- Humidity (%): 42 - 79%
Temporary deviations from the maximum level of relative humidity occurred. Laboratory historical data do not indicate an effect of the deviations.
- Air changes (per hr): approximately 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours darkness per day.

IN-LIFE DATES: From: 01-jul-2010 to 15-jul-2010

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

One day before exposure (Day -1) an area of approximately 5x7 cm on the back of the animal was clipped.

The test substance was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females. The formulation was held in contact with the skin with 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.
*. Manufacturers: Laboratoires Stella s.a., Liege, Belgium (surgical gauze) and 3M, St. Paul, Minnesota, U.S.A. (Coban & Micropore).

Frequency: Single dosage, on Day 1.

Washing: Following application, dressings were removed and the skin cleaned of residual test substance using tap water.

Duration of exposure:

24 hours.

Doses:

2000 mg/kg (2.17 mL/kg) body weight.

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Dose level (volume): 2000 mg/kg (2.17 mL/kg) body weight.
Dose volume calculated as dose level (g/kg) / specific gravity.

DOSAGE PREPARATION: The test substance was dosed undiluted as delivered by the sponsor.

Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded.
- Necropsy of survivors performed: yes
- Other examinations performed: none.

Statistics:

None.

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 deaths reported

Mortality:

No mortality occurred.

Clinical signs:

other: Chromodacryorrhoea (snout) was noted for all males and two females on Day 1 and/or 2. Flat posture was observed for two males on Day 1. No clinical signs were noted for three females. Scales were seen in the treated skin-area of one male on Day 5.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The dermal LD50 value of DIDA in Wistar rats exceeded 2000 mg/kg bw in a GLP guideline study.

Executive summary:

The acute dermal toxicity of DIDA (a structally closely-related substance) has been investigated in Wistar rats, in a limit test performed to GLP, and conducted in accordance with OECD Guideline 402.

 

Five male and five female rats were given a 24-hour dermal application of DIDA under occlusion at 2000 mg/kg bw. Animals were observed for 14 days after administration. Clinical signs of toxicity, mortality, and body weights were monitored, and survivors were subject to gross necropsy.

  

No mortalities occurred over the course of the study. Red tears were seen on the snouts of all males and two females on day 1 and/or 2, and flat posture was noted on day 1 in two males. Effects on body weight were within the expected range, and no gross abnormalities were seen at necropsy.

 

The acute dermal LD50 for DIDA was determined to exceed 2000 mg/kg bw. As a result, DIDA does not require classification for acute dermal toxicity under CLP or DSD regulations.