Dimethyl adipate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2001

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Justification for type of information:

This IUCLID for dimethyl adipate is compiled using data from the substance itself, a structurally related compound (dimethyl glutarate) and a mixture of dibasic esters (dimethyl adipate, succinate and glutarate). The toxicity of each of these substances is similar and the document attached justifies why data on the category members can be used to support the data gaps for dimethyl adipate.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

not applicable

Principles of method if other than guideline:

not applicable

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dimethyl adipate

EC Number:

211-020-6

EC Name:

Dimethyl adipate

Cas Number:

627-93-0

Molecular formula:

C8H14O4

IUPAC Name:

dimethyl adipate

Constituent 2

Reference substance name:

Hexanedioic acid, dimethyl ester

IUPAC Name:

Hexanedioic acid, dimethyl ester

Details on test material:

- Name of test material (as cited in study report): H-24926
- Physical state: clear liquid
- Impurities (identity and concentrations): Trace amounts of hydrogen cyanide (< 2 ppm)
- Composition of test material, percentage of components: > 98.5% Dimethyl adipate, < 0.1% Dimethyl succinate

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Covance Research Products, Denver, Pennsylvania
- Age at study initiation: adults
- Weight at study initiation: 1584.7 to 2230.2 grams
- Housing: The rabbits were housed singly in suspended, stainless steel, wire-mesh cages.
- Diet: The rabbits were offered approximately 125 grams of PMI Nutrition International, Inc. Certified High Fiber Rabbit LabDiet 5325 daily during the study.
- Water: ad libitum
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C ± 1°C
- Humidity (%): 50% ± 10%.
- Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark cycle

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: The area to be treated (approximately 6" x 5") was outlined on the skin of each rabbit's back with a water-insoluble marker. The aliquot of test substance designated for an animal was spread evenly, directly on the skin, covering an area of approximately 190 square centimeters.
- % coverage: approximately 10 percent of the total body surface area of rabbits in the 2 - 3 kg body weight range.
- Type of wrap if used: The test substance was covered with a 2-ply gauze patch. The rabbits were then wrapped with stretch gauze bandage and elastic adhesive bandage. This procedure was followed for each of 5 male and 5 female rabbits. After wrapping, the rabbits were returned to their cage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Approximately 24 hours after treatment, the rabbits were removed from their cages, and the wrappings were removed. Excess test substance was washed from the animals' backs with warm water, and the skin was dried with a paper towel.
- Time after start of exposure: 24 hours after treatment

TEST MATERIAL
- H-24926 was measured for each animal on the day of treatment at a dose of 1000 mg/kg of body weight. The amount of test substance designated for an animal was calculated based on body weights collected prior to treatment and the test substance density of 1064 mg/mL.

Duration of exposure:

24 hours

Doses:

1000 mg/kg body weight

No. of animals per sex per dose:

5 male + 5 female

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Approximately 24 hours after treatment, the rabbits were removed from their cages, and the wrappings were removed. Excess test substance was washed from the animals' backs with warm water, and the skin was dried with a paper towel. Approximately 1 hour after removal of the test substance, the rabbits were weighed, observed for clinical signs of toxicity and dermal response, and returned to their cages. Dermal effects were scored according to the Draize Scale.
- Necropsy of survivors performed: no

Statistics:

none

Results and discussion

Preliminary study:

not applicable

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 1 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: highest dose tested

Mortality:

No mortality was observed

Clinical signs:

other: The rabbits exhibited no clinical signs of toxicity

Gross pathology:

not performed

Other findings:

none

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

Under the conditions of this test, the skin absorption LD50 for H-24926 was greater than 1000 mg/kg of body weight for male and female rabbits and according to Annex VI of the Directive 67/548/CEE and according to EU Regulation 1272/2008 (CLP) would not be classified.

Executive summary:

A single dose of H-24926 was applied to the shaved, intact skin of 5 male and 5 female rabbits at a dose of 1000 mg/kg of body weight. The application site was semi-occluded for 24 hours, after which the test substance was removed. Observations during the 15-day test period included daily mortality checks, body weight determinations, and observations for clinical signs of toxicity and dermal irritation. No deaths occurred. The rabbits exhibited no clinical signs of toxicity or dermal irritation. Body weight loss of approximately 2-6% of initial weight occurred in 5 rabbits by the day after application of the test substance.

Under the conditions of this test, the skin absorption LD50 for H-24926 was greater than 1000 mg/kg of body weight for male and female rabbits.