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Toxicological information

Acute Toxicity: dermal

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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 guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
EPA OPP 81-2 (Acute Dermal Toxicity)
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

Constituent 1
Chemical structure
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-(hydroxymethylphosphinyl)butyrate

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.

Applicant's summary and conclusion