Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 1982-12-02 to 1982-12-22
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions. Methodology used is similar to OECD 401 and OPPTS 870.1100 (limit test) guidelines. No details on experimental conditions. Only raw data reported.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
Reliability scoring based on 2001 guideline for test n°401
Deviations:
no
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material: Sodium hypophosphite, sodium hypophosphite monohydrate
- Analytical purity: 86 % (expressed in anhydrous form NaH2PO2)
- Impurities: Phosphorous acid Anh. (NaH2PO2) 0.44 %, iron (Fe) 2.3 ppm, Heavy metals (Pb) 2 ppm, Citric acid 0.22 %
- Purity test date: 1981-11-05
- Lot/batch No.: 106
- Date of Batch: 1981-10-29
- Other: pH= 4.7
No more data available

Test animals

Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: in average 200 grams (for details see table 2 in free text of results and discussions)
- Housing: 5 rats of same sex/treatment per cage
- Diet: fasted

IN LIFE DATE: from 1982-12-08 to 1982-12-22 or from 1982-12-2 to 1982-12-16

No more data available

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE

- Amount of vehicle (if gavage): dose volumes were calculated from the fasting body weights of the rats and the selected dose volume was 10 ml/kg
body weight.


MAXIMUM DOSE VOLUME APPLIED: 10 mg/kg body weight.

Doses:
0, 2000 and 5000 mg/kg
No. of animals per sex per dose:
- 20 males and 10 females for the negative control (0 mg/kg; only water)
- 10 males for 2000 mg/kg,
- 10 males and 10 females for 5000 mg/kg
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: twice a day and weighing at 0, 7 and 14 days after exposure
- Necropsy of survivors performed: yes
No more data available
Statistics:
None

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: limit test: no mortality
Sex:
female
Dose descriptor:
approximate LD50
Effect level:
<= 5 000 mg/kg bw
Remarks on result:
other: limit test: mortality 6/10
Sex:
male
Dose descriptor:
approximate LD50
Effect level:
> 5 000 mg/kg bw
Remarks on result:
other: limit test: mortality 3/10
Mortality:
- At 2000 mg/kg , no deaths occurred in male rats.
- At 5000 mg/kg, 3 out of 10 males and 6 out 10 females died on day 2.
- In the negative control groups, no deaths occurred.
Clinical signs:
- In males exposed to 2000 mg/kg, mild depression and piloerection were observed from day 1 (1 hour after dosing) to day 2.
- In males and females exposed to 5000 mg/kg, mild depression and piloerection were observed from day 1 (immediately after dosing) to day 3.
- There were no clinical signs in the negative control groups.
Body weight:
Cf table 2 in free text of Results and discussions
Gross pathology:
- Red lungs and stomachs filled with a clear watery fluid were reported in the 3 males and 6 females found dead in the 5000 mg/kg bw groups.
- The remaining animals showed no macroscopic lesions at necropsy.

Any other information on results incl. tables

Table 1: Summarized results for cumulative mortality

Acute oral toxicity, cumulative mortality
Day Dose (mg/ kg) Sex Dose (mg/ kg) Sex Dose (mg/ kg) Sex Dose (mg/ kg) Sex Dose (mg/ kg) Sex Dose (mg/ kg) Sex
0 M 0 M 0 F 2000 M 5000 M 5000 F
Cumulative mortality Cumulative mortality Cumulative mortality Cumulative mortality Cumulative mortality Cumulative mortality
0 0/10 0/10 0/10 0/10 0/10 0/10
1 0/10 0/10 0/10 0/10  3/10  6/10
2 0/10 0/10 0/10 0/10  3/10  6/10
3 0/10 0/10 0/10 0/10  3/10  6/10
4 0/10 0/10 0/10 0/10  3/10  6/10
5 0/10 0/10 0/10 0/10  3/10  6/10
6 0/10 0/10 0/10 0/10  3/10  6/10
7 0/10 0/10 0/10 0/10  3/10  6/10
8 0/10 0/10 0/10 0/10  3/10  6/10
9 0/10 0/10 0/10 0/10  3/10  6/10
10 0/10 0/10 0/10 0/10  3/10  6/10
11 0/10 0/10 0/10 0/10  3/10  6/10
12 0/10 0/10 0/10 0/10  3/10  6/10
13 0/10 0/10 0/10 0/10  3/10  6/10
14 0/10 0/10 0/10 0/10  3/10  6/10

Table 2: Body weight summary

Acute oral toxicity,
Dose (mg/ kg) Sex Mean body weight (for 10 rats) in grams
Day 0 Day 7 Day 14
0 M 203.5 277 319.5
0 M 204.3 288 329
2000 M 204 283.3 326
5000 M 205 272 317
0 F 168 200.8 206
5000 F 170 219 237

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP ( reg 1272/2008/EC)
Conclusions:
Sodium hypophosphite is not classified according to CLP (Reg. n° 1272/2008/EC).
Executive summary:

The objective of this study was to evaluate the toxicity of Sodium Hypophosphite following a single oral administration in rats according to methods similar to OPPTS 870.1100 and OECD 401 guidelines. There were no information in the report about GLP compliance.

Sodium hypophosphite was prepared in water and was administered by gavage under a dosage-volume of 10 ml/kg bw to groups of 10 fasted rats.

Based on a previous study (not available) indicating that LD50 was greater than 1000 mg/kg in male rats, the first dose of the test item to be tested in male rats was 2000 mg/kg. The other tested dose-level administered was 5000 mg/kg (1 group of females, 1 group of males). Negative control groups receiving water only were included in the study.

Clinical signs, mortality and body weight were checked for a period of 14 days following the single administration of the test item. All animals were subjected to necropsy.

At the dose-level of 2000 mg/kg, no mortality occurred. Mild depression and piloerection were observed from day 1 (1 hour after dosing) to day 2. body weight gain was similar to controls and no apparent abnormalities were observed at necropsy

At the dose- level of 5000 mg/kg , 3 out 10 males and 6 out 10 females were found dead on day 2. At necropsy, red lungs and stomachs filled with a clear watery fluid were reported in those animals. In the surviving animals, mild depression and piloerection were observed from day 1 (immediately after dosing) to day 3. Body weight gain was similar to controls and no apparent abnormalities were observed at necropsy.

Under the experimental conditions of this study, the oral LD50 in male rats is higher than 5000 mg/kg and the oral LD50 in female rats should be included in the 2000 -5000 mg/kg bw acute toxic class.