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Acute Toxicity: oral

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acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally acceptable scientific standards with acceptable restrictions
Reason / purpose for cross-reference:
reference to same study

Data source

Reference Type:
study report

Materials and methods

Test guideline
according to guideline
other: No data
Principles of method if other than guideline:
Species: New Zealand White rabbits
Exposure: Single exposure to 0.5, 1.5, 4.5, 10.0 and 20.0 g/kg
Examinations: Mortalities, sublethal effects and necropsy
GLP compliance:
Study predates GLP
Test type:
Limit test:

Test material

Constituent 1
Chemical structure
Reference substance name:
Reaction mass of 9-icosyl-9-phosphabicyclo[3.3.1]nonane and 9-icosyl-9-phosphabicyclo[4.2.1]nonane
EC Number:
Molecular formula:
Reaction mass of 9-icosyl-9-phosphabicyclo[3.3.1]nonane and 9-icosyl-9-phosphabicyclo[4.2.1]nonane
Details on test material:
- Name of test material (as cited in study report): RM17
- Substance type: No data
- Physical state: White waxy solid at room temperature, somewhat resembling candle wax
- Analytical purity: 89.2%
- Impurities (identity and concentrations):
Light ends 0.2%
RC 78H 0.2%
1-eicosene <0.1%
RC 716 <0.1%
RC 716 oxide 0.1%
Unknown (3) 2.7%
Unknown (6) 2.8%
RM 17 oxide 4.7%
- Composition of test material, percentage of components: No data
- Isomers composition: No data
- Purity test date: 89.2%
- Lot/batch No.: Unable to define samples in terms of batch number
- Expiration date of the lot/batch: No data
- Stability under test conditions: No data
- Storage condition of test material: No data
- Other: The sample actually used to dose the animals was not analysed at the time of dosing. Subsequent analysis of the test material stored in an unsealed drum, however, showed that approximately 40% of the tertiary phosphines had been converted to oxides during several months storage. It is therefore likely that a significant amount of the test material used in the study may have been converted to the oxide during heating of the sample in preparation for dosing.

Test animals

New Zealand White
Details on test animals or test system and environmental conditions:
- Source: Ranch Rabbits, Crawley, Sussex
- Age at study initiation: No data
- Weight at study initiation: 3 - 4 kg
- Fasting period before study: The animals were unfasted
- Housing: The animals were individually housed
- Diet (e.g. ad libitum): Ad libitum throughout the 14 day observation period
- Water (e.g. ad libitum): Ad libitum throughout the 14 day observation period
- Acclimation period: No data

Administration / exposure

Route of administration:
oral: gavage
not specified
Details on oral exposure:
The animals were weighed and the calculated dose of test material was given by intraoesophageal intubation using a polythene catheter and syringe.
0.5, 1.5, 4.5, 10.0 and 20.0 g/kg
No. of animals per sex per dose:
2 male/2 female from 0.5 to 4.5 g/kg, 1 male at 10.0 and 1 male/1 female at 20.0 g/kg.
Control animals:
not specified
Details on study design:
- Necropsy of survivors performed: yes
- Other examinations performed:
After gross post mortem examination, the following tissues were taken from the animals for a detailed histopathological examination using haematoxylin and eosin, Luxol fast blue, cresyl violet and Glees and Marsland stains:
Right & left sciatic nerves (LS sections)
Right & left posterior tibial nerves (LS sections)
Spinal cord at two levels (TS sections)
Brain at three levels: Cerebellum TS, Thalmus TS and Anterior cerebrum TS

Results and discussion

Effect levels
Dose descriptor:
Effect level:
> 10 000 mg/kg bw
Both animals at the 20 g/kg dose level died, one female on Day 1 and one male on Day 4.
Clinical signs:
The surviving animal at 10 g/kg had lost bodyweight and showed moderate hyperaemia of the pyloric region on post mortem examination, but was otherwise normal.

All rabbits excreted chalk coloured faeces.

Body weight:
The survivor at 10 g/kg had lost bodyweight.
Gross pathology:
Rabbits dying following the administration of the test material had lost large quantities of blood into the gastro-intestinal tract.

Post mortem examinations showed small quantities of solidified test material in the gastro-intestinal tract, but no large "stones". The absence of large "stones" can be attributed to the fact that the rabbits were not fasted before dosing.

Applicant's summary and conclusion

Interpretation of results:
not classified
Migrated information Criteria used for interpretation of results: EU
The test item, RM-17, was administered by intraoesophageal intubation using a polythene catheter and a syringe to male and female New Zealand White rabbits at dose levels of 0.5, 1.5, 4.5, 10 and 20 g/kg. The LD50 was determined to be >10 g/kg.