Phosphonic acid, monoethyl ester, sodium salt (1:1)

Endpoint summary

Description of key information

Skin irritation (OECD 404): not irritating
Eye irritation (OECD 405): not irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

16 - 24 May 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

(adopted in July 1992) and current version of 2002

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

(adopted in July 1992)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Version / remarks:

(adopted August 1998)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Republique Francaise, Premier Ministre, Groupe Interministeriel Des Produits Chimiques, Paris Cedex, France

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CEGAV, Saint Mars d'Egrenne, France
- Weight at study initiation: 2.6 ± 0.2 kg
- Housing: individually in polystyrene cages
- Diet: 110 pelleted diet (UAR, Villemoisson, Epinay-sur-Orge, France), ad libitum
- Water: filtered water (FG Millipore membrane (0.22 micron)), ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): approx. 12
- Photoperiod (hrs dark / hrs light): (12 / 12)

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Remarks:

the gauze pad was moistened with distilled water prior to treatment to ensure good contact with the skin

Controls:

yes

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

Duration of treatment / exposure:

3 min and 4 h

Observation period:

72 h
Reading time points: 1, 24, 48 and 72 h

Number of animals:

1 male (initial test, treatment for 3 min on one flank and for 4 h on the other flank)
2 males (4 h exposure)

Details on study design:

TEST SITE
- Area of exposure: 3 min exposure: left flank (initial test animal); 4 h exposure: right flank (3 test animals)
- Type of wrap if used: The treated skin was covered by an adhesive hypoallergenic aerated dressing and a restraining bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residual test material was wiped off with a dry cotton pad.
- Time after start of exposure: 3 min (initial test animal) or 4 h

SCORING SYSTEM: Draize scoring system

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritant / corrosive response data:

Topical application of the test substance for 3 min did not induce cutaneous reactions in the initial test animal. After elongation of the exposure time to 4 h, one animal revealed a very slight erythema (scored with grade 1) visible 1 h after removal of the dressing. No skin reactions were noted at the following reading time points.

Table 1: Four -hour exposure - Individual cutaneous examinations and mean values of the scores recorded for each animal (24, 48, and 72 hours)

Observation time	Rabbit no.
	1		2		3
	Erythema	Edema	Erythema	Edema	Erythema	Edema
1 h	0	0	0	0	1	0
24 h	0	0	0	0	0	0
48 h	0	0	0	0	0	0
72 h	0	0	0	0	0	0
Mean value 24 + 48 + 72 h	0.00	0.00	0.00	0.00	0.00	0.00

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

Under the conditions chosen, the test substance did not induce skin irritation to the skin of rabbits.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23 May - 31 May 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

(adopted in February 1987)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

2012

Deviations:

yes

Remarks:

No systemic analgesic was used sixty minutes before application, local analgesic applied two minutes prior to treatment instead of five minutes, no use of systemic analgesic after treatment

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

(adopted in July 1992)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Version / remarks:

(adopted in August 1998)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Republique Francaise, Premier Ministre, Groupe Interministeriel Des Produits Chimiques, Paris Cedex, France

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: CEGAV, Saint Mars d'Egrenne, France
- Weight at study initiation: 2.8 ± 0.2 kg
- Housing: individually in polystyrene cages
- Diet: 110 pelleted diet (UAR, Villemoisson, Epinay-sur-Orge, France), ad libitum
- Water: filtered water (FG Millipore membrane (0.22 micron)), ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): approx. 12
- Photoperiod (hrs dark / hrs light): (12 / 12)

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g

Duration of treatment / exposure:

single application without washing

Observation period (in vivo):

72 h
Reading time points: 1, 24, 48 and 72 h

Number of animals or in vitro replicates:

3 males

Details on study design:

SCORING SYSTEM: Draize scoring system supplemented with scoring scale for discharge and area of opacity

TOOL USED TO ASSESS SCORE: fluorescein (on Day 2 and repeated thereafter whenever necessary)

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility not applicable

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibilty not applicable

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48

Irritant / corrosive response data:

The test item induced slight to moderate effects on the conjunctivae (redness) in 3/3 test animals scored with grade 2 in 2/3 (animal # 2 and 3) and grade 3 in 1/3 animals (animal #1) 1 h after instillation of the test substance. Moreover, chemosis was observed in 3/3 animals at the same reading time point graded with 2 (animal #2) or 3 (animal # 1 and 3). 24 h after substance instillation, chemosis was observed in 2/3 animals (grade 1) which was fully reversible at the 48 h reading time point. Effects on the conjunctivae (redness) were still visible after 24 h (animal #2, grade 1; animal #1 and 3, grade 2) or 48 h (animal #1 and 3, grade 1) but were completely reversible in all animals after 72 h at the latest. No other ocular reactions were observed in the test animals.

Other effects:

Clear to whitish purulent discharge was noted in all animals (grade 2), which was reversible latest 48 h after instillation of the test substance.

Table 1: Results of eye irritation study

Rabbit #	Time [h]	conjunctivae		iris	cornea
		redness	swelling
1	1	3	3	0	0
	24	2	0	0	0
	48	1	0	0	0
	72	0	0	0	0
	average	1.0	0.0	0.0	0.0
2	1	2	2	0	0
	24	1	1	0	0
	48	0	0	0	0
	72	0	0	0	0
	average	0.3	0.3	0.0	0.0
3	1	2	3	0	0
	24	2	1	0	0
	48	1	0	0	0
	72	0	0	0	0
	average	1.0	0.3	0.0	0.0

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

Under the conditions chosen, the test substance did not induce irritation to the eyes of rabbits.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation/corrosion

The irritancy potential of the test substance to skin was evaluated according to OECD guideline 404 and in compliance with GLP (M-211140-01-1). In an initial test, 0.5 g test substance (81.8% purity) were placed on a dry gauze pad moistened with water, which was applied to the closely-clipped skin of the left or right flank of a single New Zealand White rabbit under a semi-occlusive dressing for 3 min and 4 h, respectively. As no cutaneous reactions were observed in this animal, the test substance was topically applied for 4 h to 2 further test animals. The untreated skin served as control. The test item did not induce irritant or corrosive effects determined 1, 24, 48 and 72 h after removal of the dressing despite a very slight erythema (scored with grade 1) observed in one test animal 1 h after removal of the dressing. No other cutaneous reactions were observed until the end of the study. Mean scores evaluated over 24, 48 and 72 h were 0.0 for erythema and oedema for each animal.

Furthermore, 0.5 mL of an aqueous test solution with a content of 22.1% test substance were applied topically to the clipped skin of 3 New Zealand White rabbits under semi-occlusive dressing according to OECD Guideline 404 and GLP in a supporting study (M-207091-01-1). Dermal exposure to the test substance for 4 h did not induce cutaneous reactions in any test animal scored 1, 24, 48 and 72 h after removal of the dressing.

 

In conclusion, the test substance did not exhibit skin irritating properties in the conducted studies.

 

Eye irritation

A GLP-conform eye irritation/corrosion study was performed according to OECD Guideline 405 to evaluate the eye irritancy potential of the test substance (M-211144-01-1). Initially, a single dose of 0.1 g test substance (purity 81.1%) was instilled to the eye of one male New Zealand White rabbit without washing. As the test substance was not severely irritant, the test item was instilled in the eyes of two further rabbits after application of a local anaesthetic (Novesine® at 0.4% oxybuprocaine). The test item induced slight to moderate effects on the conjunctivae (redness) in 3/3 test animals scored with grade 2 in 2/3 and grade 3 in 1/3 animals 1 h after instillation of the test substance. Moreover, chemosis was observed in 3/3 animals at the same reading time point graded with 2 (1/3 animals) or grade 3 (2/3 animals). 24 h after substance instillation, chemosis was observed in 2/3 animals (grade 1) which was fully reversible 48 h after instillation of the test substance. Effects on the conjunctivae (redness) were still visible after 24 h (1/3 animals: grade 1; 2/3 animals: grade 2) or 48 h (2/3 animals: grade 1) but were fully reversible after 72 h at the latest. Mean values of 1/0.3/1 and 0/0.3/0.3 were derived for the effects on the conjunctival redness and chemosis induced in the test animals 1 -3, respectively, calculated over the 24, 48 and 72 h reading time points. No ocular reactions on the cornea or iris were observed.

Moreover, a single dose of 0.1 mL of an aqueous solution with a content of 22.1% test substance was applied to the eyes of 3 male New Zealand White rabbits following OECD Guideline 405 (M-207087-01-1). Instillation of the test solution induced very slight chemosis (grade 1) and conjunctival redness (grade 1) in 2/3 animals observed 1 h after substance instillation which were reversible latest 72 h after substance instillation. Mean values of 0/0.3/0 and 0/0.7/0 were derived for conjunctival redness and chemosis in the test animals 1 -3, respectively, calculated over the 24, 48 and 72 h reading time points. No further ocular reactions were determined until the end of the observation period.

 

In conclusion, the test substance did not exhibit eye irritating properties in the conducted studies.

Justification for classification or non-classification

The available data on skin and eye irritation of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.