Reaction mass of 9-icosyl-9-phosphabicyclo[3.3.1]nonane and 9-icosyl-9-phosphabicyclo[4.2.1]nonane

Acute Toxicity: other routes

Administrative data

Endpoint:

acute toxicity: other routes

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: STudy does not follow a guideline or GLP but is otherwise well documented.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Materials and methods

Principles of method if other than guideline:

The objective of the study was to determine the acute percutaneous toxicity of RM-17, both molten (50°C) and in organic solvents. The acute (24 h) percutaneous LD50 was determined.

GLP compliance:

no

Remarks:

Predates GLP

Limit test:

no

Test material

Test material information

Constituent 1

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:

915-206-4

Molecular formula:

C28H55P

IUPAC Name:

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): RM-17
- Physical state:Solid

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Shell Toxicology Laboratory (Tunstall) Breeding Colony.
- Age at study initiation: 4-5 months
- Housing: Hanging stainless steel cages with all mesh flooers and tops and half mesh fronts of dimensions 58 x 43 x 43 cm, mounted six to a rack. Sawdust filled trays for excreta were placed beneath each tray and changed twice weekly.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: Minimum of 14 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20± 2°C
- Humidity::55 ± 5%
- Air changes (per hr): 15
- Photoperiod: 12 hrs dark / 12 hrs light

Administration / exposure

Route of administration:

other: percutaneous

Details on exposure:

24 hours prior to the test animals were weighed and approximately 60% of the dorsal hair closely shorn with fine electric clippers. The skin was finally visually inspected immediately before application of the test chemical to ensure that all microabrasions of the stratum corneum had healed.

The calculated dose was applied to the shorn skin by syringe, the dose being altered by varying the volume of constant concentration injection material. The application site was left unoccluded and oral ingestion was prevented by fitting each rabbit with a plastic collar which remained in place throughout the experiment. Molten RM-17 was applied at 40-50°C; the solutions were dosed at room temperature.

Doses:

1800 mg/kg of RM-17 at 45-50°C
5% w/v solution of RM-17 in n-butanol at a dose level of 100 mg/kg
25% w/v solution of RM-17 in toluene at a dose level of 500 mg/kg

No. of animals per sex per dose:

3

Details on study design:

- Duration of observation period following administration: 28 days
- Frequency of observations and weighing: Initial and weekly bodyweights were recorded.

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 1 800 mg/kg bw

Based on:

other: Molten RM-17 at 45-50°C

Effect levels 2

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 100 mg/kg bw

Based on:

other: 5% w/v solution of RM-17 in n-butanol

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 500 mg/kg bw

Based on:

other: 25% (w/v) solution of RM-17 in toluene

Mortality:

There were no mortalities at any of the doses tested.

Clinical signs:

RM-17 at 45-50°C at a dose level of 1800 mg/kg:
All animals showed signs of irritation and eventual shedding of skin at the site of application but there were no other signs of toxicity.
On day 14, one female which had been severly stressed by the collar was killed, but there were no signs of toxicity due to RM-17 in this animal.


5% w/v solution of RM-17 in n-butanol at 100 mg/kg
All animals showed irritation, scabbing and eventual skin loss at the site of application. No signs of systemic toxicity were observed. The animals ate and gained body weight at the usual rate.

25% w/v solution of RM-17 in toluene at 500 mg/kg:
All animals showed signs of irritation, ridging and cracking of the skin at the site of application. Leading eventually to some shedding of the skin.
 No signs of systemic toxicity were observed. The animals ate and gained bodyweight at the usual rate. 

Applicant's summary and conclusion

Conclusions:

The acute percutaneous LD50 of RM-17 at 45-50°C was > 1800 mg/kg.
The acute percutaneous LD50 of 5% (w/v) solution of RM-17 in n-butanol was > 100 mg/kg
The acute percutaneous LD50 of 25% (w/v) solution of RM-17 in toluene was > 500 mg/kg