hexasodium (R)-carboxy(phosphono)methanolate (S)-carboxy(phosphono)methanolate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Read-across

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Test material

Test material information

Constituent 1

Details on test material:

- Name of test material (as cited in study report): TK 13061/A
- Physical state: Solid
- Analytical purity: 100%
- Lot/batch No.: Ex BX P807040

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CIBA-GEIGY Ltd, Animal production
- Age at study initiation: 6-8 weeks
- Weight at study initiation: 181-234 grams
- Housing:Macrolon cage, type 4
- Diet (e.g. ad libitum): Rat chow (NAFAG 890 tox) ad libitum
- Water (e.g. ad libitum): water provided ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2 C
- Humidity (%): 55 +/- 10%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hour/day light cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

one single oral dose, by gastric gavage in distilled water vehicle (10 ml/kg bw).

Doses:

500 mg/kg, males
1000 mg/kg, males and females
2000 mg/kg, males

No. of animals per sex per dose:

total number of animals: 20

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: Body weight measured immediately before administration, on days 7, 14 and at death.

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

1 260 mg/kg bw

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

> 1 000 - < 2 000 mg/kg bw

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 383 mg/kg bw

Mortality:

No deaths reported at 500 and 1000 mg/kg doses.
At 2000 mg/kg dose: 2 rats died on day 1, 1 rat died on day 2, 1 rat died on day 4 and 1 rat died on day 5.

Clinical signs:

Piloerection, hunched posture and dyspnoea.

In one male and one female of the 1000 mg/kg dose group, respiratory sounds were noticed. Reduced locomotor activity and chromodacryorrhea were noticed in the animals of the 2000 mg/kg dose group. One animal of the same dose group experienced diarrhoea on day 1 to day 4 and ventral recumbency on day 4 after administration.

Gross pathology:

In animals of the 2000 mg/kg dose group a liquid-filled thoracic and/or abdominal cavity and spotted lungs or thymus were found. The stomach was spotted or dilated.

Applicant's summary and conclusion

Interpretation of results:

sligthly toxic

Remarks:

Migrated information

Conclusions:

LD50 in male rats: 1260 mg/kg bw
LD50 in female rats: > 1000 mg/kg bw
LD50 rats of both sexes: 1383 mg/kg bw

Executive summary:

In an acute oral toxicity study, a group of 20 male/female, 6 -8 week old Tif: RAI Sprague Dawley derived rats were given a single oral dose of  Pure hydroxyphosphonoacetic acid at doses of  500 mg/kg (males only), 1000 mg/kg (males and females) 2000 mg/kg (males only) and observed for 14 days.

 

Oral LD₅₀ Males =  1260 mg/kg bw

      Females = >1000 - < 2000 mg/kg bw

      Combined =  1383 mg/kg  bw

Pure hydroxyphosphonoacetic acid is of low Toxicity based on the LD₅₀ in females.