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Toxicological information

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:
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:
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

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
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 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:
The rabbits exhibited no clinical signs of toxicity
Body weight:
Body weight loss of approximately 2-6% of initial weight occurred in 5 rabbits by the day after application of the test substance.
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.