Ammonium 2-amino-4-(hydroxymethylphosphinyl)butyrate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EPA OPP 81-2 (Acute Dermal Toxicity)

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

no

Remarks:

The study was subjected to Quality Assurance inspections and is of acceptable quality.

Test type:

standard acute method

Test material

Test material information

Constituent 1

Reference substance name:

Ammonium 2-amino-4-(hydroxymethylphosphinyl)butyrate

EC Number:

278-636-5

EC Name:

Ammonium 2-amino-4-(hydroxymethylphosphinyl)butyrate

Cas Number:

77182-82-2

Molecular formula:

C5H12NO4P.H3N

IUPAC Name:

ammonium 2-amino-4-[hydroxy(methyl)phosphoryl]butanoate

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Froxfield Rabbits, Petersfield, Hampshire, England
- Age at study initiation: 9-13 weeks
- Weight at study initiation: 2.1-2.8 kg
- Housing: individually in metal cages with perforated floors
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: min. 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-21
- Humidity (%): 46-76%
- Air changes (per hr): 19
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Remarks:

distilled

Details on dermal exposure:

TEST SITE
- % coverage: 10%
- Type of wrap if used: gauze fastened with an impermeable dressing encircled firmly around the trunk

REMOVAL OF TEST SUBSTANCE
- Washing (if done): warm (30-40°C) water
- Time after start of exposure: 24 hours

Duration of exposure:

24 hours

Doses:

1500, 2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: observations: 30 min after dosing, then hourly for 6 hours and at least twice per day on the subsequent days. Bodyweights were recorded on day 1 (dosing), 8, 15 (or at death)
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic examination

Results and discussion

Preliminary study:

Preliminary study indicated that the LD50 was above 2000 mg/kg bw

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 2 000 mg/kg bw

Mortality:

2000 mg/kg bw: 2/5 males and 3/5 females died
1500 mg/kg bw: no mortalities

Clinical signs:

There were no dermal reactions at the site of application in any of the treated animals.
Animals treated at 2000 mg/kg bodyweight appeared normal on the day of dosing. Signs of intoxication to treatment were first observed on
Day 2 of the study. These signs were pilo-erection, unsteady gait, lethargy and ataxia. The rabbits were in a collapsed state at this time. Reactions seen shortly after dosing in rabbits treated at 1500 mg/kg were pilo-erection, unsteady gait and lethargy.
Recovery of survivors as judged by external appearance and behaviour was generally complete in animals treated at 1500 mg/kg bodyweight by Day 3 and in animals treated at 2000 mg/kg bodyweight between Days 5 and 7. One male rabbit 736 (2000 mg/kg bodyweight) still showed
pilo-erection on Day 7 and was still thin in appearance on Day 14. A further male rabbit 1410 (1500 mg/kg bodyweight) was not eating on
Days 5 and 6.

Body weight:

A bodyweight loss was recorded on Day 8 for one male (2000 mg/kg bodyweight) and one male (1500 mg/kg bodyweight) and on
Day 15 for one male and one female (2000 mg/kg bodyweight).
Bodyweight gains were recorded for all other surviving rabbits on Days 8 and 15.

Gross pathology:

Autopsy amongst rabbits dosed at 2000 mg/kg bodyweight revealed pale areas on liver lobes containing purulent material in one male and areas of consolidation in the left lung of one male.
All other autopsy findings were normal.