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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
2006-09-05 to 2006-11-06
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
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:
2006
Report Date:
2006

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
See information in the field "Confidential details on test material"

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
The animals were nulliparous and non-pregnant. After an acclimatisation period of at least five days the animals were selected at random and given a number unique within the study by indelible ink-marking on the tail and a number written on a cage card. At the start of the study the animals were eight to twelve weeks of age. The bodyweights fell within an interval of ± 20% of the mean initial bodyweight of the first treated group.

The animals were housed in groups of three in suspended solid-floor polypropylene cages furnished with woodflakes. With the exception of an overnight fast immediately before dosing and for approximately three to four hours after dosing, free access to mains drinking water and food was allowed throughout the study. The diet, drinking water and bedding were routinely analysed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.

The temperature and relative humidity were set to achieve limits of 19 to 25°C and 30 to 70% respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 4.96 ml/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: based on available historical data/information
Doses:
5000 mg/kg
No. of animals per sex per dose:
3 female animals
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: 30 min, 1h, 2h, 4h, then daily up to 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
Hunched posture and pilo-erection were noted in one animal two days after dosing and in one animal three days after dosing. Animals appeared normal three or four days after dosing.
Body weight:
Animals showed expected gain in bodyweight over the study period.
Gross pathology:
No abnormalities were noted at time of necropsy.

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated to be greater than 5000 mg/kg bodyweight. Therefore DBE is not classified according to Annex VI of the Directive 67/548/CEE and according to EU Regulation 1272/2008 (CLP).
Executive summary:

DBE has been tested in an acute oral toxicity study using female Sprague Dawley rats, according to OECD guideline n° 423 and EU guideline n° B.1 tris in compliance with Good Laboratory Practice.

The test item was administered without vehicle once by oral route (gavage) to a group of three fasted female rats at a dose level of 5000 mg/kg.

Clinical signs, mortality and body weight gain were checked for a period of up to 14 days after the single administration of DBE. All animals were subjected to necropsy.

No mortality was recorded during the study. Body weight gain of the treated animals was not affected by treatment. At necropsy, no abnormalities were observed in any animal.

As the LD 50 is higher than 5000 mg/kg, DBE is not classified according to Annex VI of the Directive 67/548/CEE and according to EU Regulation 1272/2008 (CLP).