Ammonium 2-amino-4-(hydroxymethylphosphinyl)butyrate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPP 81-3 (Acute inhalation toxicity)

GLP compliance:

yes

Test type:

traditional 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:

rat

Strain:

Wistar

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hoechst AG, Kastengrund, SPF breeding colony
- Age at study initiation: 8-10 weeks
- Weight at study initiation: males 163-193 g, females 174-193 g
- Housing: in fully air-conditioned rooms in Makrolon cages (Type 4) on softwood granulate in groups of 5 animals
- Diet (e.g. ad libitum): rat diet Altromin 1324 (Altromin GmbH, Lage/Lippe), ad libitum
- Water (e.g. ad libitum): tap water in plastic bottles, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 50 +/- 20
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

>= 0.6 - <= 10.3 µm

Details on inhalation exposure:

The rats were placed individually in cylindrical plastic tubes and exposed to specified dust concentrations for 4 hours. The plastic tubes leading into the exposure cylinder are so arranged that only the noses of the animals are inside the cylinder. The inhalation chamber itself consists of a stainless steel and glass cylinder with a volume of 60 L, standing in a vent pipe with a volume of ca. 4 m3. Particles of test substance escaping from the exposure
chamber into the vent pipe are drawn off and neutralized by gas-cleaning equipment.
The dust was produced with the aid of a "Wright Dust Feed" generator manufactured by L. Adams Ltd., London. The different concentrations were achieved by adjusting the gear transmission ratios. The dust produced by the scraper head was drawn from above into the exposure chamber by a current of air flowing at a rate of 1000 L/h at 4 bar.
A suction device at the bottom of the inhalation chamber drew off the dust at a rate of 1000 L/h through a cotton-wool filter and a washing bottle filled with water.

Remarks on duration:

4 hours

Concentrations:

0.12, 0.19, 0.38, 2.0 mg/L

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weighing took place on days 2, 3, 4, 7 and 14 after exposure
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic examination, behavioural tests

Statistics:

The LC 50, the 95 % range of confidence and the equation of the probit lines were assessed on the basis of the actual death rates by probit analysis (according to the method of UNDER and WEBER); the limits of confidence were calculated according to the method of FIELLER or SIDAK (program supplied by the Department Praktische Mathematik of HOECHST A6)

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LC50

Effect level:

1.26 mg/L air

Effect levels 2

Sex:

female

Dose descriptor:

LC50

Effect level:

2.6 mg/L air

Mortality:

0.12 mg/L: 0/10
0.19 mg/L: 1/10
0.38 mg/L: 2/10
2.0 mg/L: 5/10

Clinical signs:

other: The following clinical signs of intoxication were observed: narrowed eye openings, periodic tremors and clonic convulsions, hyperactivity, pilo-erection, increased salivation and passivity.

Body weight:

A reduction of bodyweights was recorded in the male and female animals during the days immediately after inhalation, to a greater extent with increasing concentrations. All surviving animals had regained their initial weight on day 14 after inhalation.

Gross pathology:

Autopsy of the animals which died during and of those killed at the end of the study revealed no macroscopically visible changes.