Dilithium sebacate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

16 April to 21 May 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-compliant, guideline study, available as an unpublished report.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Dilithium adipate

EC Number:

242-449-7

EC Name:

Dilithium adipate

Cas Number:

18621-94-8

Molecular formula:

C6H8O4.2Li

IUPAC Name:

dilithium adipate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Physical state: White powder
- Purity: 100%
- Substance identity: FLTL G14058
- Batch number: A049/99
- Expiration date: 2018-03-06
- Storage of test material: Room temperature in the dark

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

- Source: Charles River Deutschland, Sulzfeld, Germany. Animals were 8 to 10 weeks old and nulliparous and non-pregnant.
- Acclimatisation: The acclimatization period was at least 5 days before the start of treatment under laboratory conditions and animals were group housed.
- Housing: Individual housing of animals in the pilot study and group housing of four animals per cage in the main study in labeled Makrolon cages (MIV type; height 18 cm.) containing sterilized sawdust as bedding material and paper as cage-enrichment. The rats had free access to pelleted rodent diet and tap water.
- Environmental conditions: Temperature and relative humidity were set to achieve limits of 18 to 24 deg C, and 40 to 70% humidity. Rate of air exchange was at least 10 changes per hour and there was a 12 hour light/12 hour dark cycle.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

- Preparation: The preparations (w/w) were kept at room temperature protected from light and were dosed within 4 hours after adding the vehicle to the test substance. Homogeneity was obtained to visually acceptable levels.
- Dosing: Oral gavage, using plastic feeding tubes. The test item preparations were stirred on a magnetic stirrer during dosing. The concentration of the test substance in vehicle was varied to allow constant dosage volume in terms of mL/kg body weight.

Doses:

In the absence of any other toxicity information a "Pilot study" was conducted in which single female rats were orally dosed with the test substance at 2000 or 300 mg/kg body weight. Based on the Pilot results, a fixed dose level was selected for the main study and four further females were dosed at 300 mg/kg body weight.

No. of animals per sex per dose:

For the main study a total of five female rats (including the pilot study rat) were treated at a single dose concentration.

Control animals:

no

Details on study design:

- Observations: Clinical observations were made on the day of dosing and then once daily until Day 15. Morbidity and viability checks were made twice daily and individual body weights were recorded on days 0, 8 and 15. 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.

Statistics:

The Fixed Dose Procedure does not require any statistical analyses of the data.

Results and discussion

Preliminary study:

In the preliminary study at 2000 mg/kg bw with a single animal, the animal was found dead on Day 2. At 300 mg/kg bw no mortality of the single animal occured. Hunched posture and piloerection were noted at both treatment levels, up to day 6 at 300 mg/kg bw.

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 mg/kg bw

Based on:

test mat.

Mortality:

During the definitive study, there were no deaths.

Clinical signs:

other: Hunched posture and piloerection were noted for all animals on Day 1.

Gross pathology:

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

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The highest dose level of Dilithium adipate that did not produce mortality in Wistar rats was established as 300 mg/kg body weight and the estimated minimum lethal dose level was 2000 mg/kg body weight. Based on the mortality rate at 2000 mg/kg body weight, it was concluded that the oral LD50 value of Dilithium adipate was within the range of 300-2000 mg/kg body weight. Based on these results Dilithium adipate should be classified as Category 4.

Executive summary:

The acute oral toxicity of Dilithium adipate to female Wistar rats was determined in a GLP-compliant, fixed-dose method study following OECD guideline 420 (Latour 2015). A preliminary study indicated mortality of a single rat at 2000 mg/kg bw Dilithium adipate but no mortality of a single rat at 300 mg/kg bw Dilithium adipate. For the definitive test four further rats were treated once with 300 mg/kg bw Dilithium adipate by oral gavage and observed for the following 15 days for mortality, systemic toxicity and bodyweight gain. No deaths or significant signs of toxicity were seen. The LD50 value is within the ranges 300 -2000 mg/kg bw Dilthium adipate. Based on these results Dilithium adipate should be classified as Category 4. The study is considered to be relevant and reliable for use for this endpoint.