Registration Dossier

There were no data for irritation/corrosion with Potassium phosphinate however studies to test the irritant potential of Sodium hypophosphite were available as follows:

- an in vivo dermal irritation test in rabbits (performed according to 49 CFR Part 173.240 method from the US Hazardous Materials Regulations. This method was comparable to the OECD 404 guideline issued in 1981. The study predates GLP requirements).

- an in vivo eye irritation test in rabbits (method comparable to EPA 870.2400 and OECD 405 guidelines, GLP compliance not stated in the study report).

Based on these studies, Sodium hypophosphite is considered to be non-irritant for skin and eyes.

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

no precise data, 72 hours minimum

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study with acceptable restrictions performed using a method equivalent to the OECD guideline 404. No data on the purity of the tested substance, no observation period for the reversibility and no scoring at 60 minutes after patch removal.

Qualifier:

according to guideline

Guideline:

other: DOT, Hazardous Materials Regulations, 49 CFR Part 173.240

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

. Reliability scoring based on 1981 OECD guideline for test n° 404.

Deviations:

yes

Remarks:

: no observation period for reversibility, no scoring at 60 minutes after patch removal.

GLP compliance:

no

Remarks:

study predates GLP requirements.

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2530 - 3167 grams

No more data available

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: each animal served as its own control

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 500 milligrams by rabbit on shaved backs (intact or abraded sites)

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3 males and 3 females

Details on study design:

TEST SITE
- Type of wrap if used: occlusive
- Testing area: intact (shaved) and abraded skins

REMOVAL OF TEST SUBSTANCE
- Washing: tepid tap water
- Time after start of exposure: 4 hours

SCORING SYSTEM: according to OECD guideline 404

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 24, 72 hours

Score:

<= 0.6

Irritation parameter:

erythema score

Remarks:

Test item applied onto intact skin

Basis:

animal #1

Time point:

other: mean of the 24, 48 and 72-hour readings

Score:

0.66

Max. score:

4

Reversibility:

no data

Irritation parameter:

erythema score

Remarks:

Test item apllied onto the intact skin

Basis:

animal #2

Time point:

other: mean of the 24, 48 and 72-hour readings

Score:

0.66

Max. score:

4

Reversibility:

no data

Irritation parameter:

erythema score

Remarks:

Test item applied onto the intact skin

Basis:

animal #3

Time point:

other: mean of the 24, 48 and 72-hour readings

Score:

1

Max. score:

4

Reversibility:

no data

Irritation parameter:

edema score

Remarks:

Test item applied onto the intact skin

Basis:

animal #1

Time point:

other: mean of the 24, 48 and 72-hour readings

Score:

0

Max. score:

4

Irritation parameter:

edema score

Remarks:

test item applied onto the intact skin

Basis:

animal #2

Time point:

other: mean of the 24, 48 and 72-hour readings

Score:

0

Max. score:

4

Irritation parameter:

edema score

Remarks:

Test item applied onto the intact skin

Basis:

animal #3

Time point:

other: mean of the 24, 48 and 72-hour readings

Score:

0.33

Max. score:

4

Reversibility:

no data

Irritant / corrosive response data:

For raw data see tables in the "remarks on results" freetext.

Raw data for irritant/corrosive response:

Each animal was evaluated according to the grading scale of theOECD 404 guideline.

Table 1: Primary skin irritation scoring values

		Intact skin				Abraded skin
		Hours				Hours
Observations	Grade	4	24	48	72	4	24	48	72
Erythema, Eschar formation	0				2/3	2/3			1/3
	1	3/3	3/3	3/3	1/3	1/3	3/3	3/3	2/3
	2
	3
	4
Edema Formation	0	3/3	3/3	3/3	2/3	3/3	3/3	3/3	3/3
	1				1/3
	2
	3
	4

Table 2: Corrosion results

	Intact skin				Abraded skin
	Hours				Hours
Observations	4	24	48	72	4	24	48	72
Necrosis (corrosion)	0/3	0/3	0/3	0/3	0/3	0/3	0/3	0/3

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: other: CLP (Reg. 1272/2008/EC)

Conclusions:

Under the experimental conditions of this study and according to the criterai laid down in CLP (Reg 1272/2008/EC), the test item Sodium hypophosphite is considered as non-irritant to the skin.

Executive summary:

The potential of sodium hypophosphite to induce skin irritation or corrosion was assessed in adult New Zealand white rabbits (3 males and 3 females) using the 49 CFR Part 173.240 method from the US Hazardous Materials Regulations. This method was comparable to the OECD 404 guideline issued in 1981. The study predates GLP requirements.

The rabbits were dermally exposed to 500 mg of sodium hypophosphite for 4 hours on prepared shaved backs. 3 animals received the test item onto an intact skin while the remaining received the test item onto an abraded area.The test substance was held in contact with the skin by means of an occlusive dressing. Cutaneous reactions were observed 24, 48 and 72 hours after removal of the dressing.

A slight erythema (scoring value 1) was observed in all animals at the 24 -hour reading and was still persistent in 1out 3 animals treated onto an intact skin and 2 out 3 animals treated on an abraded area at the 72 -hour reading. Only one animal with intact skin showed a slight oedema (soring value 1) at the 72 -hour reading.

According to the criteria laid down in EC regulation 1272/2008/EC, Sodium hypophosphite is considered as non-irritant to the skin and is not classified.

Endpoint conclusion:

no adverse effect observed (not irritating)

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 1982-03-09 to 1982-03-19

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions. Methodology used is similar to OECD 405 and OPPTS 870.2400 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 870.2400 (Acute Eye Irritation)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

. Reliability scoring based on 1981 OECD guideline for test n°405

Deviations:

no

GLP compliance:

not specified

Species:

rabbit

Strain:

not specified

Details on test animals or tissues and environmental conditions:

IN-LIFE DATES: From: 1982-03-09 To: 1982-03-16 (or 1982-03-19 for one animal)
No more data available

Vehicle:

unchanged (no vehicle)

Controls:

other: each animal served as its own control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg

Duration of treatment / exposure:

Single exposure

Observation period (in vivo):

Ten days which was the duration needed to clear all ocular effects.

Number of animals or in vitro replicates:

9 rabbits ( 6 animals with eyes not washed after instillation of the test item and 3 animals with eyes washed after instillation of the test item).

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: yes, for 3 animals
- Time after start of exposure: unknown

SCORING SYSTEM: cf free text of materials and methods. Grading scale used is equivalent to the one used in OECD 405.
No more data available

Irritation parameter:

cornea opacity score

Remarks:

: Eyes not rinsed

Basis:

mean

Remarks:

: 6 animals

Time point:

other: mean of the 24, 48 and 72 hours readings

Score:

0

Max. score:

4

Irritation parameter:

iris score

Remarks:

: Eyes not rinsed

Basis:

mean

Remarks:

: 6 animals

Time point:

other: mean of the 24, 48 and 72 hours readings

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Remarks:

: (Redness) Eyes not rinsed

Basis:

mean

Remarks:

: 6 animals

Time point:

other: mean of the 24, 48 and 72 hours readings

Score:

0.89

Max. score:

3

Reversibility:

fully reversible within: 10 days

Irritation parameter:

chemosis score

Remarks:

: Eyes not rinsed

Basis:

mean

Remarks:

: 6 animals

Time point:

other: mean of the 24, 48 and 72 hours readings

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 3 days

Irritation parameter:

cornea opacity score

Remarks:

: Eyes rinsed

Basis:

mean

Remarks:

: 3 animals

Time point:

other: mean of the 24, 48 and 72 hours readings

Score:

0

Max. score:

4

Irritation parameter:

iris score

Remarks:

: Eyes rinsed

Basis:

mean

Remarks:

: 3 animals

Time point:

other: mean of the 24, 48 and 72 hours readings

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Remarks:

: (redness) Eyes rinsed

Basis:

mean

Remarks:

: 3 animals

Time point:

other: mean of the 24, 48 and 72 hours readings

Score:

0.66

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Remarks:

: Eyes rinsed

Basis:

mean

Remarks:

: 3 animals

Time point:

other: mean of the 24, 48 and 72 hours readings

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 4 days

Irritant / corrosive response data:

Without rinsing, a slight (grade1) and fully reversible (within 10 days) redness of the conjunctivae was observed in all rabbits. A slight chemosis
(grade 1) was present in 4 out of 6 rabbits but the reaction cleared within 3 days.
The washing procedure did not modify the ocular reactions. All animals showed a slight (grade 1) and transient redness of the conjunctivae. Chemosis was observed in 1 out 3 animals but the reaction cleared within 4 days.
No lesions of cornea or iris were reported whatever the procedure od treatment. (See Table 1 for complete raw data)

Table 1: Synthesis of the raw results

Scores per animal	Observation	Pre-dose	Day 1	Day 2	Day 3	Day 4	Day 7	Day 10
Eyes not rinsed (6 animals)	Cornea opacity (0-4)	0/0/0/0/0/0	0/0/0/0/0/0	0/0/0/0/0/0	0/0/0/0/0/0	0/0/0/0/0/0	0/0/0/0/0/0	nd/0
	Cornea area (0-4)	0/0/0/0/0/0	0/0/0/0/0/0	0/0/0/0/0/0	0/0/0/0/0/0	0/0/0/0/0/0	0/0/0/0/0/0	nd/0
	Iris (0-2)	0/0/0/0/0/0	0/0/0/0/0/0	0/0/0/0/0/0	0/0/0/0/0/0	0/0/0/0/0/0	0/0/0/0/0/0	nd/0
	Conjonctivae redness (0-3)	0/0/0/0/0/0	1/1/1/1/1/1	1/1/1/1/1/1	1/0/1/1/1/0	1/0/0/1/1/1	0/0/0/0/0/1	nd/0
	Conjonctivae chemosis (0-4)	0/0/0/0/0/0	0/0/1/1/1/0	0/0/1/1/0/1	0/0/0/0/0/0	0/0/0/0/0/0	0/0/0/0/0/0	nd/0
	Conjonctivae discharge (0-3)	0/0/0/0/0/0	1/1/1/1/1/1	1/1/1/1/0/0	0/1/1/1/0/0	0/1/1/1/1/0	0/0/0/0/0/0	nd/0
Total		0/0/0/0/0/0	4/4/6/6/6/4	4/4/6/6/2/4	2/2/4/4/2/0	2/2/2/4/2	0/0/0/0/0/2
Eyes rinsed (3 animals)	Cornea opacity (0-4)	0/0/0	0/0/0	0/0/0	0/0/0	0/0/0	0/0/0	nd
	Cornea area (0-4)	0/0/0	0/0/0	0/0/0	0/0/0	0/0/0	0/0/0	nd
	Iris (0-2)	0/0/0	0/0/0	0/0/0	0/0/0	0/0/0	0/0/0	nd
	Conjonctivae redness (0-3)	0/0/0	1/1/1	0/1/1	0/1/0	0/1/0	0/0/0	nd
	Conjonctivae chemosis (0-4)	0/0/0	0/0/1	0/0/1	0/0/1	0/0/0	0/0/0	nd
	Conjonctivae discharge (0-3)	0/0/0	2/1/1	0/0/1	0/0/1	0/0/1	0/0/0	nd
Total		0/0/0	6/4/6	0/2/6	0/2/4	0/2/2	0/0/0

To obtain subtotal for the cornea multiply the product of the opacity and area scores by 5. For the iris subtotal multiply the score by 5 and for conjunctivae multiply the sum of the scores (redness, chemosis and discharge) by 2.

Total: sum of all subtotals per animal

Table 2: Irritant/corrosive response data of each animal except washed animals according to OPPTS and OECD guidelines scoring system

Score at time point/ Reversibility	Cornea Max. score: 4	Iris Max. score: 2	Conjunctivae Redness Max. score: 3	Conjunctivae Chemosis Max. score: 4
24 h	0/0/0/0/0/0	0/0/0/0/0/0	1/1/1/1/1/1	0/0/1/1/1/0
48 h	0/0/0/0/0/0	0/0/0/0/0/0	1/1/1/1/1/1	0/0/1/1/0/1
72 h	0/0/0/0/0/0	0/0/0/0/0/0	1/0/1/1/1/0	0/0/0/0/0/0
Average 24h, 48h, 72h	0	0	0.89	0.33
Reversibility*	-	-	c.(10 days)	c.

* c.=completely reversible

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: other: CLP (Reg. 1272/2008/EC)

Conclusions:

Under the experimental conditions of this study and according to the criterai laid down in CLP (Reg 1272/2008/EC), the test item Sodium
hypophosphite is considered as non-irritant to the eyes.

Executive summary:

The potential of Sodium hypophosphite to induce eye irritation was assessed in 9 rabbits according to methods similar to OPPTS 870.2400 and OECD 405 guidelines. There were no information in the report about GLP compliance.

A single dose of 100 mg of the test item was instilled into one eye, the other eye was not treated and served as control. For 6 rabbits, the eyes were not rinsed after administration of the test item while a washing procedure was applied for 3 other animals .Ocular reactions were observed 24, 48 and 72 hours after the administration and then daily until reversibility of the ocular reactions. The values of the scores for chemosis, redness of the conjunctiva, iris lesions and corneal opacity were noted for each animal.

Mean scores calculated over 24, 48 and 72 hours for the 6 animals without rinsing were 0.33 for chemosis, 0.89 for redness of the conjunctiva, 0 for iris lesions and 0 for corneal opacity. Redness and chemosis were fully reversible within 10 and 3 days respectively.

Washing procedure did not change the ocular reactions.

Under these experimental conditions,Sodium hypophosphite was considered non- irritant when administered by ocular route to rabbits.

Endpoint conclusion:

no adverse effect observed (not irritating)

Endpoint conclusion:

no study available

Data for Sodium hypophosphite:

Skin irritation/corrosion:

One valid study is recorded for this endpoint and was chosen as key study (Wilson, 1977).

The potential of sodium hypophosphite to induce skin irritation or corrosion was assessed in rabbits using the 49 CFR Part 173.240 method from the US Hazardous Materials Regulations. This method was comparable to the OECD 404 guideline issued in 1981. The study was performed before the implementation of GLP.

Six rabbits were dermally exposed to 500 mg of sodium hypophosphite for 4 hours. 3 received the test item onto an intact skin while the remaining received the test item onto an abraded area. The test substance was held in contact with the skin by means of an occlusive dressing. Cutaneous reactions were observed 24, 48 and 72 hours after removal of the dressing. No observation and no scoring were performed after 72 hours.

A slight erythema (scoring value 1) was observed in all animals at the 24 -hour reading and was still persistent in 1out 3 animals treated onto an intact skin and 2 out 3 animals treated on an abraded area at the 72 -hour reading. Only one animal with intact skin showed a slight oedema (scoring value 1) at the 72 -hour reading.

Based on these results and according to the criteria laid down in EC regulation 1272/2008/EC and EU directive 67/548/EEC, Sodium hypophosphite is considered as non-irritant to the skin and is not classified.

Eye irritation:

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

The potential of Sodium hypophosphite to induce eye irritation was assessed in 9 rabbits according to methods similar to OPPTS 870.2400 and OECD 405 guidelines. There were no information in the report about GLP compliance.

A single dose of 100 mg of the test item was instilled into one eye, the other eye was not treated and served as control. For 6 rabbits, the eyes were not rinsed after administration of the test item while a washing procedure was applied for 3 other animals .Ocular reactions were observed 24, 48 and 72 hours after the administration and then daily until reversibility of the ocular reactions. The values of the scores for chemosis, redness of the conjunctiva, iris lesions and corneal opacity were noted for each animal.

Mean scores calculated over 24, 48 and 72 hours for the 6 animals without rinsing were 0.33 for chemosis, 0.89 for redness of the conjunctiva, 0 for iris lesions and 0 for corneal opacity. Redness and chemosis were fully reversible within 10 and 3 days respectively.

Washing procedure did not change the ocular reactions.

Based on these results and according to the criteria laid down in EC regulation 1272/2008/EC and EU directive 67/548/EEC, Sodium hypophosphite is considered as non-irritant when administered by ocular route and is not classified.

According to the criteria laid down in EU regulation (EC) n°1272/2008 (CLP) and EU Directive 67/548/EEC, Potassium phosphinate has not to be classified for skin irritation/corrosion nor eye irritation.