Registration Dossier

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

Reference
Name:
Unnamed
Type:
Constituent
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 levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
1 260 mg/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
> 1 000 - < 2 000 mg/kg bw
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.