Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
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:
2017
Report Date:
2017

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: Young adult animals (approx. 10 weeks)
- Weight at study initiation: Animlas of comparable weight (+/- 20% of the mean weight)
- Fasting period before study: at least 16 hours before administration
- Housing: single housing (Makrolon cage, type III)
- Diet (e.g. ad libitum): VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany, ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: at least 5 days before the beginning of the experimental phase

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 30 - 70 %
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Deionized water
Doses:
300 and 2000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,pathology

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
In the first 2000 mg/kg bw test group no mortality occurred.
In the second 2000 mg/kg bw test group one animal died on study day 2 and one animal was sacrificed in a moribund state on study day 6.
No mortality occurred in both 300 mg/kg bw test groups.
Clinical signs:
In all animals of the first 2000 mg/kg bw test group impaired general state and piloerection were observed from hour 1 or 2 until study day 3 after administration. In addition, reduced defecation was noted in two animals from hour 5 until day 1 or on study day 1.
Loss of body weight was seen in all animals on study day 2 and persisted in two animals until study day 3. In one animal chromodacryorrhea was noted on study day 1, while exsiccosis was seen in this animal on study day 1 and 3. In this animal lack of defecation was observed on study day 3.
In all animals of the second 2000 mg/kg bw test group impaired general state and piloerection were noted from hour 0 or 3 until study day 1, 3 or 6. Poor general state was observed in one of these animals on study day 6. In addition, dyspnoea was seen in two animals on study day 1 and was noted again in one of these animals on study day 6. Cowering position was noticed in the same 2 animals on study day 1. Furthermore, reduced defecation was seen in two animals on study day 1 and persisted in one of theses animals until study day 3. In another animal this finding was seen on study day 6. Exsiccosis was seen in two animals from study day 3 until study day 6, while loss of body weight was noticed in these animals on study day 3 and persisted in one animal until study day 6. In only one animal of the first 300 mg/kg bw test group impaired general state and piloerection were observed from hour 3 until hour 4 after administration. In addition, dyspnoea was noted in this animal at hour 3. No clinical signs were observed in the other 2 animals.
In the second 300 mg/kg bw test group no clinical signs were observed during clinical examination.
Body weight:
The body weight of the animals in the first and second 2000 mg/kg bw test group decreased within the first 2, 3 or 6 days after administration. Thereafter, the body weights increased in the surviving animals in a normal range, although two of these animals did not reach their initial weight during the first observation week. In the second week, the body weights increased within the normal range.
Body weights of the 300 mg/kg bw test groups increased within the normal range with one exception in the second 300 mg/kg bw test group. This animal gained weight in a normal range during the first observation week but the body weight only slightly increased during the second week. This effect is observed at times in the rat strain used, because in the required age range the female animals have already reached the phase of slow growth.
Gross pathology:
In the animal that died in the second 2000 mg/kg bw test group red discoloration of the glandular stomach and small intestine were observed during necropsy. In another animal of this test group, that was sacrificed in a moribund state on study day 6, no macroscopic pathological findings were observed. There were no macroscopic pathological findings in the surviving animals sacrificed at the end of the observation period (2000 mg/kg bw 4 females; 300 mg/kg bw 6 females).

Any other information on results incl. tables

Mortality

Dose (mg/kg bw):

2000

2000

Sex:

female

female

Administration:

1

2

No. of animals:

3

3

Sacrificed moribund:

-

1

Mortality (animals)

No mortality

1

Mortality

Dose (mg/kg bw):

300

300

Sex:

female

female

Administration:

1

2

No. of animals:

3

3

Mortality (animals)

No mortality

No mortality

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Under the conditions of this study the median lethal dose of Phosphorwolframic acid hydrate after oral administration was found to be greater than 300 mg/kg bw and less than 2000 mg/kg bw in rats.