Potassium phosphinate

Endpoint summary

Description of key information

There were no acute toxicity for Potassium phosphinate however acute toxicity studies were available for Sodium phosphinate also named Sodium hypophosphite and can be used for read across as follows:

- an acute oral toxicity test in rats (method comparable to EPA 870.1100 and OECD 401 guidelines, GLP compliance not stated in the study report)
- an acute dermal toxicity test in rabbits (method comparable to EPA 870.1200 and OECD 402 guidelines, GLP compliance not stated in the study report)
Sodium hypophosphite is of low acute toxicity following oral exposure:
The oral LD50 was found to be greater than 5000 mg/kg bw in male rats. The oral LD50 in female rats was found to be lower than 5000 mg/kg bw and should be included in the 2000-5000 mg/kg bw acute toxic class.
Sodium hypophosphite is of low acute toxicity following dermal exposure:
The dermal LD0 was determined to be equal or greater than 2000 mg/kg bw in rabbits.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

equivalent or similar to guideline

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

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system 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

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

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.

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

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Good; the study is compliant with Reach guidance requirements

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 1984-05-15 to 1984-05-29

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Comparable guideline study with acceptable restrictions. Methodology used is similar to OECD guideline 402 and guideline OPPTS 870.1200 (limit test) with deviations (less than 5 animals tested). No details on experimental conditions. Only raw data reported.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

less than 5 animals tested with intact skin

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

Reliability scoring based on 1987 guideline for test n°402

Deviations:

yes

Remarks:

less than 5 animals tested with intact skin

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation:
Control rabbits mean weight: 2033 grams
Dosed rabbits mean weight: 1798 grams
For details: see table 2 in free text of results and discussions

IN-LIFE DATES: From: 1984-05-15 to 1984-05-29
No more data available

Type of coverage:

not specified

Vehicle:

not specified

Details on dermal exposure:

TEST MATERIAL
- Amount(s) applied: 2000 mg/kg body weight
No more data available

Duration of exposure:

24 hours

Doses:

One dose at 2000 mg/kg (limit dose)

No. of animals per sex per dose:

- Negative controls: 2 males and 2 females with for each sex 1 with abraded skin and 1 with intact skin
- 2000 mg/kg bw: 5 males (3 of which with abraded skin ) and 5 females (2 of which with abraded skin)

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 0, 7 and 14 days after exposure
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology and behaviour

Statistics:

No data

Sex:

male/female

Dose descriptor:

LD0

Effect level:

>= 2 000 mg/kg bw

Mortality:

No deaths were observed during the study.
cf table 1 in results and discussions free text

Clinical signs:

No systemic clinic signs were observed during the study at the dose-levels of 2000 mg/kg. Moderate erythema and mild to moderate oedema were observed on removal of the dressing. These local reactions cleared within 24 hours.
There were no effects in the control group.

Body weight:

cf table 2 in results and discussions free text

Gross pathology:

No abnormalities were observed at macroscopic examination.

Summarized results:

Table 1: Summarized results for combined sex of cumulative mortality

Acute dermal toxicity, 24h exposure, cumulative mortality
Day	Dose (mg/ kg)	Sex	Dose (mg/ kg)	Sex
	0	M/F	2000	M/F
	Cumulative mortality		Cumulative mortality
0	0/4		0/10
1	0/4		0/10
2	0/4		0/10
3	0/4		0/10
4	0/4		0/10
5	0/4		0/10
6	0/4		0/10
7	0/4		0/10
8	0/4		0/10
9	0/4		0/10
10	0/4		0/10
11	0/4		0/10
12	0/4		0/10
13	0/4		0/10
14	0/4		0/10

Applicant's remark: 5 animals per sex have been tested. however some were tested on abraded skin. Therefore, the minimum number of tested animals is not achieved. The results show no mortality nor clinical signs whatever the sex and the abraded or intact skin. So, the deviation of the number of animals tested is considered as minor and the LD0 > 2000 mg/kg bw can be used for the classification

Table 2: Summarized results for body weight

Acute dermal toxicity, 24h exposure
Skin status	Dose (mg/ kg)	Sex	Mean body weight in grams
			Day 0	Day 7	Day 14
Intact	0	M	1794	2050	2259
Abraded	0	M	1714	2049	2338
Intact	0	F	2352	2528	2756
Abraded	0	F	2272	2456	2662
Intact	2000	M	1789	1909	2163
Abraded	2000	M	1846	2046	2275
Intact	2000	F	1750	1946	2151
Abraded	2000	F	1808	2033	2336

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 dermal application to rabbits

according to methods similar to OPPTS 870.1200 and OECD 402 guidelines. There were no information in the report about GLP compliance.

The test item was applied to the skin of one group of five males (3 with abraded and 2 with intact skin) and five females (2 with abraded and 3 with intact skin) at the dose-level of 2000 mg/kg bw. One group of 2 males and 2 females acts as a control group (1 male and 1 female with abraded skin, 1 male and 1 female with intact skin).The test site was then covered by dressing for 24 hours. Clinical signs, mortality and body weight gain were checked for a period of 14 days following the single application of the test item. All animals were subjected to necropsy.

Neither mortality nor systemic clinical signs were observed during the study. A moderate erythema and a mild to moderate oedema were observed on removal of the dressing and cleared within 24 hours. The body weight gain of the animals was not affected by treatment compared to controls. No apparent abnormalities were observed at necropsy in any animal.

Under these experimental conditions, the dermal LD₀of Sodium hypophosphite was equal or higher than 2000 mg/kg in rabbits

.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Good; the study is compliant with Reach guidance requirements

Additional information

Data from Sodium phosphinate also named sodium hypophosphite :

Acute oral toxicity

One study is reported for this endpoint and was chosen as a key study.

The acute oral toxicity was performed using a methodology similar to EPA OPPTS 870.1100 and OECD 401guidelines.There were no information in the report about GLP compliance.

Sodium hypophosphite was administered at dose-levels of 2000 and 5000 mg/kg bw to male rats. Females rats received only the highest dose.

Negative control groups receiving water only were included in the study.

there were no deaths in the controls and in the 2000 mg/kg bw dosed group while 3 out of 10 males and 6 out of 10 females were found dead at the 5000 mg/kg bw dose. At necropsy, red lungs and stomachs filled with a clear watery fluid were reported in the animals found dead. In the treated surviving animals, mild depression and piloerection were observed from day 1 to day 2 and from day 1 to day 3 in the 2000 mg/kg bw and 5000 mg/kg bw dosed groups respectively . 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 was 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.

Acute dermal toxicity

One study is reported for this endpoint and was chosen as a key study.

The acute dermal toxicity was performed using a methodology similar to EPA OPPTS 870.1200 and OECD 402 guidelines.There were no information in the report about GLP compliance.

Sodium hypophosphite was applied to the skin of five males and five females at the dose-level of 2000 mg/kg bw. One group of 2 males and 2 females acts as a control group.

Neither mortality nor systemic clinical signs were observed during the study. A moderate erythema and a mild to moderate oedema were observed on removal of the dressing and cleared within 24 hours. The body weight gain of the animals was not affected by treatment compared to controls. No apparent abnormalities were observed at necropsy in any animal.

Under these experimental conditions, the dermal LD₀ of Sodium hypophosphite was equal or higher than 2000 mg/kg in rabbits

Justification for classification or non-classification

According to the criteria laid down in EU regulation (EC) n° 1272/2008/EC (CLP) and EU directive 67/548/EEC, Potassium phosphinate does not have to be classified for acute toxicity.