Castor oil, hydrogenated, lithium salt

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

6 December 2012 to 3 January 2013

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other: GLP-compliant, guideline study, available as an unpublished report.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

2013

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:

Lithium myristate

EC Number:

243-743-8

EC Name:

Lithium myristate

Cas Number:

20336-96-3

IUPAC Name:

lithium myristate

Test material form:

other: Solid

Details on test material:

- Physical state: White solid
- Purity: >99%
- Substance identity: 10634 Lithium myristate, synthetic sample
- Batch number: 10074
- Analysis code: A194/99
- Expiration date: 2012-12-31
- 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: Harlan laboratories UK Ltd., Oxon, UK. Animals were 8 to 12 weeks old and nulliparous and non-pregnant.
- Acclimatisation: On receipt, animals were randomly assigned to cages. After at least 5 days acclimatisation, animals were selected at random and marked with a unique identifier for the test in indelible ink.
- Housing: Animals were housed in groups of four in suspended solid-floor polypropylene cages furnished with woodflakes. With the exception of an overnight fast immediately before doing and for approximately 3 to 4 hours after dosing, the animals had free access to mains drinking water and food.
- Environmental conditions: Temperature and relative humidity were set to achieve limits of 19 to 25 deg C, and 30 to 70% humidity. Rate of air exchange was at least 15 changes per hour and the lighting controlled by a time switch to give 12 hours light/12 hours darkness. Animals were provided with enrichment items.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

- Preparation: The lithium myristate did not dissolve or suspend in distilled water, it was freshly prepared as a suspension in arachis oil BP and applied to the test system within 2 hours of formulation. As an exception with regard to GLP, the homogeneity, concentration or stability or the formulation were not analysed but it was assumed that the formulation was stable for the duration until use.
- Dosing: Animals were dosed once only by gavage with 10 mL/kg dose volumes using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted body weight at the time of dosing.

Doses:

In the absence of data regarding the toxicity of lithium myristate, a preliminary study with a single animal was conducted at 300 mg/kg bw. As no effects were observed, an additional animal was treated at 2000 mg/kg bw. In the absence of evident toxicity at a dose level of 2000 mg/kg bw, four additional animals were dosed sequentially at this dose level.

No. of animals per sex per dose:

Five female rats were treated at a single dose concentration.

Control animals:

no

Details on study design:

- Observations: Clinical observations were made at 30 mins, 1, 2 and 4 hours after dosing, then daily for 14 days. Morbidity and mortality checks were made twice daily and individual body weights were recorded on days 0, 7 and 14. At the end of the exposure, animals were killed by cervical dislocation and subject to gross necropsy by external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded but no tissues were retained.

Statistics:

Evaluation of data included identification of the number of animals which died or were killed for humane reasons and the determination of the nature, severity, onset and duration of the toxic effects. The mortality data obtained were used to estimate the acute oral median lethal dose.

Results and discussion

Preliminary study:

In the preliminary study at 300 mg/kg bw with a single animal, there was no death and no signs of systemic toxicity during the observation period and at test termination, no abnormalities were noted at necroscopy. The animal showed the expected gains in bodyweight over the observation period.

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

During the definitive study, there were no deaths.

Clinical signs:

other: at 2000 mg/kg bw/day the initial treated animal showed diarrhoea two hours after dosing but there were no signs of systemic toxicity noted in the remaining animals.

Gross pathology:

During necropsy, hydrophrosis was noted of two animals. No abnormalities were noted at necropsy of the remaining animals.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral median lethal dose (LD50) of lithium myristate in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight and therefore, lithium myristate is considered not to meet the criteria for classification under the CLP Regulation.

Executive summary:

The acute oral toxicity of lithium myristate to female Wistar rats was determined in a GLP-compliant, fixed-dose method study following OECD guideline 420. Five rats were treated once with 2000 mg/kg bw lithium myristate by oral gavage and observed for the following 14 days for mortality, systemic toxicity and bodyweight gain. No deaths or significant signs of toxicity were seen. The LD50 value is > 2000 mg/kg bw/day. The study is considered to be relevant and reliable for use for this endpoint.