Phosphinic acid

Endpoint summary

Description of key information

The dermal and ocular irritant potential of phosphinic acid was assessed using a non-animal testing based on alkaline reserve.
This method can be used at first step of stepwise strategy for assessing cutaneous and ocular irritation.
An amount of the test substance is added to distilled water in a beaker. The solution or suspension is maintained for 4 hours with agitation at 37° C. The pH is directly measured and the sample is then titrated with diluted sodium hydroxyde or hydrochloric acid until neutrality is obtained. The acidic or alkaline reserve (R) is expressed as the number of grams of pure acid or base necessary to neutralise 100 g of product (%). 
Under the test conditions, the aqueous phosphinic acid shows an acidic character demonstrated by a pH of 0,71 for a 100 g/L solution in water, an alkaline reserve of 38,015 (i.e log R = 1,580) and a physicochemical index of 14,870.
According to the method described, as all the criteria are fullfilled, Phosphinic acid can be considered as potentially corrosive to the skin and severely irritant to the eye.
Skin corrosive potantial of Phosphinic Acid was assesed by The Corrositex Assay. 4 vials of 50% Phosphinic Acid solution was used in the test with negative and positive control samples. A membrane disc was placed on the top of the vials and the test item is evenly applied onto the top of the membrance discs. The vial was observed for 3 minutes for any change in the CDS. A one minute interval was left between each treatment. The vials were observed continuously for the first 10 minutes, and at approximate 5 minute intervals for 240 minutes (Category 1 test items) or until breakthrough of
the test item had occurred. The first indication of breakthrough of the test item was detected as achange, either in colour or in physical appearance, in the CDS compared to the negative control. The average breakthrough point is observed as  12 min 05 sec. According to this result Phosphinic Acid is considered as H314 Cat 1B (CLP)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation / corrosion, other

Remarks:

other: alkaline reserve

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Test procedure in accordance with generally accepted scientific standards and described in sufficient detail.

Qualifier:

no guideline available

Principles of method if other than guideline:

Supplement of guidelines 404 and 405 recommends the sequential testing strategy (including pH and alkaline reserve measurements) prior to undertaking the in vivo tests corrosion/irritation of the substance.
The method used in the study which permits the measurement of pH and Alkaline reserve to identify chemicals potentially corrosive to the skin and to the eye was described in V.Froment (1993) and JF.Regnier & C. Imbert (1992), respectively.

Criteria for eye irritation:
The test item is considered at potentially severely irritant to the eye if at least 2 of the 3 following criteria are fulfilled:
- pH <= 2,5 / pH >= 9,5
- log R >= 0, with the R corresponding to the alkaline reserve
- I >= 9, with the I corresponding to the physicochemical index, defined as a weighting of the pH by the decimal logarithm of the Alkaline reserve
I = pH + log R for pH >= 7
I = (14 - pH) + log R for pH < 7

Criteria for skin corrosion :
The test item is corrosive to the skin if at least 2 of the 3 following criteria are fulfilled:
- pH <= 2,5 or pH >= 9,5
- log R >= 0
- I >= 10

GLP compliance:

yes (incl. QA statement)

Species:

other: no species

Strain:

not specified

Irritation parameter:

other: pH, alkaline reserve R, physicochemical index I

Basis:

other: pH, alkaline reserve R, physicochemical index I

Time point:

other: pH

Score:

0.71

Remarks on result:

other: for a 100 g/L solution in water

Irritation parameter:

other: pH, alkaline reserve R, physicochemical index I

Basis:

other: pH, alkaline reserve R, physicochemical index I

Time point:

other: alkaline reserve R

Score:

38.015

Remarks on result:

other: log R = 1.580

Irritation parameter:

other: pH, alkaline reserve R, physicochemical index I

Basis:

other: pH, alkaline reserve R, physicochemical index I

Time point:

other: physicochemical index I

Score:

14.87

Irritant / corrosive response data:

Under the test conditions, the aqueous phosphinic acid shows an acidic character demonstrated by a pH of 0.71 for a 100 g/L solution in water, analkaline reserve of 38,015 (i.e log R = 1,580) and a physicochemical index of 14,870.

According to the method, the test item is considered:
- as potentially corrosive to the skin as the 3 criteria are fullfilled.
pH <= 2,5 or pH >= 9,5
log R >= 0
I >= 10
- as potentially severely irritant to the eye as the 3 criteria are fullfilled.
pH <= 2,5 or pH >= 9,5;
log R >= 0
I >= 9

As the 3 criteria are fullfilled for both end-points, hypophosphorous acid can be considered as potentially corrosive to the skin and severely irritant to the eye.

Under the test conditions, the aqueous phosphinic acid shows an acidic character demonstrated by a pH of 0.71 for a 100 g/L solution in water, an alkaline reserve of 38,015 (i.e log R = 1,580) and a physicochemical index of 14,870.

Table 1 : Results of neutralization experiments

Replicate	Hypophorous acid 100 g/L, mL	NaOH 0,1 N, mL	Initial pH	Final pH	R	Log (R)	I
1	10	95,110	0,71	7,01	38,015	1,580	14,870
2	10	95,160	0,71	7,04
3	10	95,190	0,71	7,01

Interpretation of results:

corrosive

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

According to the method, the test item is considered:
- as potentially corrosive to the skin as the 3 criteria are fullfilled.
pH <= 2,5 or pH >= 9,5
log R >= 0
I >= 10
- as potentially severely irritant to the eye as the 3 criteria are fullfilled.
pH <= 2,5 or pH >= 9,5;
log R >= 0
I >= 9

As the 3 criteria are fullfilled for both end-points, phosphinic acid can be considered as potentially corrosive to the skin and severely irritant to the eye.

Executive summary:

The pH and Alkaline reserve of the test item phosphinic acid was measured according to the method described in the two following references JF.Regnier and C.Imbert (1992), and V.Froment (1993).

Criteria for eye irritation:

The test item is considered at potentially severely irritant to the eye if at least 2 of the 3 following criteria are fulfilled:

- pH <= 2,5 / pH >= 9,5

- log R >= 0, with the R corresponding to the alkaline reserve

- I >= 9, with the I corresponding to the physicochemical index, defined as a weighting of the pH by the decimal logarithm of the Alkaline reserve

I = pH + log R for pH >= 7

I = (14 - pH) + log R for pH < 7

Criteria for skin corrosion :

The test item is corrosive to the skin if at least 2 of the 3 following criteria are fulfilled:

- pH <= 2,5 or pH >= 9,5

- log R >= 0

- I >= 10

This method can be used at first step of stepwise strategy for assessing cutaneous and ocular irritation.

An amount of the test substance is added to distilled water in a beaker. The solution or suspension is maintained for 4 hours with agitation at 37° C. The pH is directly measured and the sample is then titrated with diluted sodium hydroxide or hydrochloric acid until neutrality is obtained. The acidic or alkaline reserve (R) is expressed as the number of grams of pure acid or base necessary to neutralise 100 g of product (%).

A preliminary titration was performed for a preliminary test to allows good conditions for the alkaline reserve (R) determination: 10 mL volume of a 100 g/L solution are neutralised by approximately 95 mL of 0.1 N NaOH. Then for a definitive test, the titration were performed three times more in the same conditions.

Under the test conditions, the aqueous phosphinic acid shows an acidic character demonstrated by a pH of 0.71 for a 100 g/L solution in water, an alkaline reserve of 38.015 (i.e log R = 1,580) and a physicochemical index of 14.870.

According to the method described, as all the criteria are fullfilled, Phosphinic acid can be considered as potentially corrosive to the skin and severely irritant to the eye.

Reference 2

Endpoint:

skin corrosion: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 2013/11/22 to 2013/12/19

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study following OECD guideline without deviation

Qualifier:

according to guideline

Guideline:

OECD Guideline 435 (In Vitro Membrane Barrier Test Method for Skin Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

2012/11/30

Species:

other: Biobarrier membrane (reconstituted collagen matrix)

Strain:

not specified

Amount / concentration applied:

500 µL

Duration of treatment / exposure:

240 minutes

Observation period:

The vials were observed continuously for the first 10 minutes, and at approximate 5 minute intervals for 240 minutes (Category 1 test items) or until breakthrough of the test item had occurred.

Details on study design:

Negative Control: Citric Acid, prepared as a 10% w/v solution
+ Batch: 117130
+ Purity: 99.5%
+ Expiry Date: 15 March 2015
+ Storage Conditions: room temperature

Positive Control: Sulphuric Acid
+ Batch: 1331156
+ Purity: >95%
+ Expiry Date: 15 March 2018
+ Storage Conditions: room temperature

Qualification Screen
The qualification screen was used to determine whether the assay was suitable for the test item. For the qualification screen 150 μL of the test item was added to the "Qualify" test tube. If the test item failed to produce a color or physical change in the qualifying test within five minutes, it cannot be analyzed with the CORROSITEX®.

Categorization Screen
The categorization screen was used to enable the test item to be measured against the appropriate classification scale. Test items having high acid/alkaline reserves are defined as ‘Category 1’ items, while those with low acid/alkaline reserves are defined as ‘Category 2’ items.
The screen was performed by adding 150 μL of the test item to each tube (A and B). Each tube was agitated and the resulting colours observed. The categorisation kit and colour chart provided by In Vitro International were used to determine the category.

Biobarrier Preparation
The membrane discs were prepared three days prior to the assay and were refrigerated at 2 to 8 °C overnight before use. Biobarriers are stable for seven days if wrapped and stored at 2 to 8 °C.
A scintillation vial containing the biobarrier matrix powder was placed in a water bath on a hot plate set at 68 to 70 °C, with the stir switch set to maintain a steady rate for the stir-bar. The entire contents of the biobarrier diluent vial were added slowly to the biobarrier matrix powder to ensure complete and uniform solubilisation. The solution was warmed to 68 to 70 °C to solubilise the biobarrier matrix.

Irritation / corrosion parameter:

other: other: Breakthrough Time

Value:

12

Remarks on result:

other:

Remarks:

Basis: other: cells viability. Max. score: 240.0. Reversibility: not reversible. Remarks: the test was stopped after 12 minutes and 5 secondes because of the corrosion effects. (migrated information)

Qualification Screen

The test item produced an immediate color change and therefore qualified for use in the CORROSITEX® assay.

Categorization Screen

The test item was assigned into Category 1

The results of the test:

	Vial 1	Vial 2	Vial 3	Vial 4
Start time (hr:min:sec)	00:00:00	00:04:00	00:05:00	00:06:00
Detection time (hr:min:sec)	00:12:00	00:17:30	00:16:30	00:17:20
Breakthrough time (hr:min:sec)	00:12:00	00:13:30	00:11:30	00:11:20

Mean Breakthrough time of the four test item replicates: 12 minutes 05 seconds

Positive/Negative Controls Quality Criteria

The results of the assay were accepted on condition of adherence to the positive and negative control item ranges given in the following table:

 

	Chemical	Concentration (weight %)	Breakthrough Time (hr:min:sec)
Positive control	Sulphuric acid	95-98	00:01:08
Negative control	Citric Acid	10	No breakthrough observed

 

Interpretation of results:

Category 1B (corrosive)

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test item was considered to be CORROSIVE. The following classification criteria apply:
UNITED NATIONS PACKING GROUP II.
EU CLP code H314 hazard category 1B

Executive summary:

The Corrositex® assay is a standardized and quantitative in vitro corrosivity test. The potential corrosivity of the test item was assessed by measuring the time that is required for the test item to pass through a biobarrier membrane and produce a change in a Chemical Detection System (CDS).

4 vials of 50% Hypophosphorous acid solution used in the test. According to the results (average breakthrough point: 12 min 05 sec) the substance is considered to be CORROSIVE. The following classification criteria apply:

UNITED NATIONS PACKING GROUP II.

EU CLP code H314 hazard category 1B

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation, other

Remarks:

other: alkaline reserve

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Test procedure in accordance with generally accepted scientific standards and described in sufficient detail.

Qualifier:

no guideline available

Principles of method if other than guideline:

Supplement of guidelines 404 and 405 recommends the sequential testing strategy (including pH and alkaline reserve measurements) prior to undertaking the in vivo tests corrosion/irritation of the substance.
The method used in the study which permits the measurement of pH and Alkaline reserve to identify chemicals potentially corrosive to the skin and to the eye was described in V.Froment (1993) and JF.Regnier & C. Imbert (1992), respectively.

Criteria for eye irritation:
The test item is considered at potentially severely irritant to the eye if at least 2 of the 3 following criteria are fulfilled:
- pH <= 2,5 / pH >= 9,5
- log R >= 0, with the R corresponding to the alkaline reserve
- I >= 9, with the I corresponding to the physicochemical index, defined as a weighting of the pH by the decimal logarithm of the Alkaline reserve
I = pH + log R for pH >= 7
I = (14 - pH) + log R for pH < 7

Criteria for skin corrosion :The test item is corrosive to the skin if at least 2 of the 3 following criteria are fulfilled:
- pH <= 2,5 or pH >= 9,5
- log R >= 0
- I >= 10

GLP compliance:

yes (incl. QA statement)

Irritation parameter:

other: pH, alkaline reserve R, physicochemical index I

Basis:

other: pH, alkaline reserve R, physicochemical index I

Time point:

other: pH

Score:

0.71

Remarks on result:

other: for 100g/L solution in water

Irritation parameter:

other: pH, alkaline reserve R, physicochemical index I

Basis:

other: pH, alkaline reserve R, physicochemical index I

Time point:

other: alkaline reserve R

Score:

38.015

Remarks on result:

other: log R = 1.580

Irritation parameter:

other: pH, alkaline reserve R, physicochemical index I

Basis:

other: pH, alkaline reserve R, physicochemical index I

Time point:

other: physicochemical index I

Score:

14.87

Irritant / corrosive response data:

Under the test conditions, the aqueous phosphinic acid shows an acidic character demonstrated by a pH of 0.71 for a 100 g/L solution in water, analkaline reserve of 38,015 (i.e log R = 1,580) and a physicochemical index of 14,870.

According to the method, the test item is considered:
- as potentially corrosive to the skin as the 3 criteria are fullfilled.
pH <= 2,5 or pH >= 9,5
log R >= 0
I >= 10
- as potentially severely irritant to the eye as the 3 criteria are fullfilled.
pH <= 2,5 or pH >= 9,5;
log R >= 0
I >= 9

As the 3 criteria are fullfilled for both end-points, hypophosphorous acid can be considered as potentially corrosive to the skin and severely irritant to the eye.

Under the test conditions, the aqueous phosphinic acid shows an acidic character demonstrated by a pH of 0.71 for a 100 g/L solution in water, an alkaline reserve of 38.015 (i.e log R = 1.580) and a physicochemical index of 14.870.

Table 1 : Results of neutralization experiments

Replicate  Hypophorous acid 100 g/L, mL  NaOH 0,1 N, mL Initial pH  Final pH   R  Log (R)  I  1  10 95,110  0,71  7,01         38,015   1,580      14,870     2  10 95,160 0,71 7,04  3  10 95,190 0,71 7,01

Interpretation of results:

highly irritating

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

According to the method, the test item is considered:
- as potentially corrosive to the skin as the 3 criteria are fullfilled.
pH <= 2,5 or pH >= 9,5
log R >= 0
I >= 10
- as potentially severely irritant to the eye as the 3 criteria are fullfilled.
pH <= 2,5 or pH >= 9,5;
log R >= 0
I >= 9

As the 3 criteria are fullfilled for both end-points, phosphinic acid can be considered as potentially corrosive to the skin and severely irritant to the eye.

Executive summary:

The pH and Alkaline reserve of the test item phosphinic acid was measured according to the method described in the two following references JF.Regnier and C.Imbert (1992), and V.Froment (1993).

Criteria for eye irritation:

The test item is considered at potentially severely irritant to the eye if at least 2 of the 3 following criteria are fulfilled:

- pH <= 2,5 / pH >= 9,5

- log R >= 0, with the R corresponding to the alkaline reserve

- I >= 9, with the I corresponding to the physicochemical index, defined as a weighting of the pH by the decimal logarithm of the Alkaline reserve

I = pH + log R for pH >= 7

I = (14 - pH) + log R for pH < 7

Criteria for skin corrosion :

The test item is corrosive to the skin if at least 2 of the 3 following criteria are fulfilled:

- pH <= 2,5 or pH >= 9,5

- log R >= 0

- I >= 10

This method can be used at first step of stepwise strategy for assessing cutaneous and ocular irritation.

An amount of the test substance is added to distilled water in a beaker. The solution or suspension is maintained for 4 hours with agitation at 37° C. The pH is directly measured and the sample is then titrated with diluted sodium hydroxide or hydrochloric acid until neutrality is obtained. The acidic or alkaline reserve (R) is expressed as the number of grams of pure acid or base necessary to neutralise 100 g of product (%).

A preliminary titration was performed for a preliminary test to allows good conditions for the alkaline reserve (R) determination: 10 mL volume of a 100 g/L solution are neutralised by approximately 95 mL of 0.1 N NaOH. Then for a definitive test, the titration were performed three times more in the same conditions.

Under the test conditions, the aqueous phosphinic acid shows an acidic character demonstrated by a pH of 0.71 for a 100 g/L solution in water, an alkaline reserve of 38.015 (i.e log R = 1.580) and a physicochemical index of 14.870.

According to the method described, as all the criteria are fullfilled, Phosphinic acid can be considered as potentially corrosive to the skin and severely irritant to the eye.

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The pH and Alkaline reserve of the test item phosphinic acid was measured according to the method described in the two following references JF.Regnier and C.Imbert (1992), and V.Froment (1993).

Criteria for eye irritation:

The test item is considered at potentially severely irritant to the eye if at least 2 of the 3 following criteria are fulfilled:

- pH <= 2,5 / pH >= 9,5

- log R >= 0, with the R corresponding to the alkaline reserve

- I >= 9, with the I corresponding to the physicochemical index, defined as a weighting of the pH by the decimal logarithm of the Alkaline reserve

I = pH + log R for pH >= 7

I = (14 - pH) + log R for pH < 7

Criteria for skin corrosion :

The test item is corrosive to the skin if at least 2 of the 3 following criteria are fulfilled:

- pH <= 2,5 or pH >= 9,5

- log R >= 0

- I >= 10

The skin irritation potantial of Phosphinic Acid is assessed by The Corrositex Assay. The criteria for classification is as follows

Corrosive	I	1A	0 -3
Corrosive	II	1B	>3 -60
Corrosive	III	1C	>60 -240
Non-Corrosive	Not applicable	Not classified for corrosivity	>240

According to the test the the Mean Breakthrough time of 4 samples was observed as 12 min 05 sec. So, the criteria of classification H314 hazard category 1B was fulfilled.

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Justification for classification or non-classification

According to the method described, as all the criteria are fullfilled, Phosphinic acid is classified (following the CLP Regulation EC N° 1272/2008) as:

- Skin corrosive, Category 1B

- Eye Damage, Category 1

According to The Corrositex Assay results the test item was considered to be CORROSIVE. The following classification criteria apply:

UNITED NATIONS PACKING GROUP II.

EU CLP code H314 hazard category 1B