Reaction mass of isopropyl dihydrogen phosphate and phosphoric acid and propan-2-ol

Endpoint summary

Description of key information

Skin irritation: 2 in vivo studies available: corrosive; 1 in vitro study available: corrosive, Cat 1B

Eye irritation: 2 studies available: corrosive

 

There are two in vivo studies and one in vitro study available on the skin irritancy potential. A 1:10 dilution of the test item was tested for its skin irritant properties in 3 or 5 Yellow-silver strain rabbits. The studies were similar to OECD Guideline 404. Effects on the skin (bloody and cracky skin) were observed in most of the animals after application. Therefore, it is concluded that the undiluted registration substance is corrosive.
In a Corrositex test performed with the test item, the substance was applied to an artificial bio-barrier membrane In this study under the given conditions the test substance showed corrosive effects. The test substance is classified as “CORROSIVE”, subcategory 1B according to the UN GHS, as the mean time to activate the CDS was > 3 – 60 min (category 1). The test substance is therefore assigned to Packing Group 2 and to EU Risk-Phrase (R 34).

There are in vivo two studies available on the eye irritancy potential. A 1:10 dilution of test item was tested for its eye irritant properties in 3 or 5 Yellow-silver strain rabbits. The studies were similar to OECD Guideline 405.

The application of a 1:10 dilution of the test substance to the eyes of rabbits lead to slight to moderate opacity, reddening and swelling of the conjunctivae.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin corrosion: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2014-12-04 to 2014-12-05

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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:

Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit, Germany

Test system:

artificial membrane barrier model

Source species:

other: Bio-barrier membrane

Details on animal used as source of test system:

n.a.

Justification for test system used:

commonly accepted for classication of corrosive substances to Cat. 1A, 1B or 1C

Vehicle:

unchanged (no vehicle)

Details on test system:

This assay is composed of three different steps:

1. Qualification
This step ensures that the sample is compatible with the CORROSITEX™ system. 150 µL of the test substance are added to the Qualify test tube. Solids are shaken to dissolve, if necessary. For immiscible liquids and insoluble solids the vial is shaken and let stand for one minute. If the colour or consistency of the CDS changes at the sample/testing fluid interface, the test material is qualified for the assay. If no reaction is observed within five minutes, the sample is not qualified for the CORROSITEX™ Assay.

2. Categorisation
This step establishes the category for cut-off times for the sample. 150 µL of the test substance are added to the tubes labeled Tube A and Tube B. After shaking a colour change in either of the tubes is matched to the corresponding colour charts on the CORROSITEX™ Testing Protocol Poster. Test materials having high acid/alkaline reserves are defined as Category 1 materials, while those with low acid/alkaline reserves are defined as Category 2 materials. If no colour change is observed in either tube, CONFIRM reagent is added to Tube B. After shaking, the resulting colour is matched to the colour chart on the CORROSITEX™ Testing Protocol Poster.
If the test item has strong colouring or shows other characteristics impairing a clear categorization according to the colour chart, the pH value can be measured in the tubes A and B and is used to confirm/determine the category of the test item

3. Classification
This step determines the appropriate Packing Group for the test sample. The CDS vials are warmed to room temperature (17 - 25˚C) before using. Vials 1 - 4 are utilized for sample replicate testing.The vial labeled (+) was utilized for a positive control sample, the vial labeled (-) for a negative control. The vial labeled C served as a CDS colour control. One BIOBARRIER disc was added on top of the first vial. 500 µL of the test item were applied by five steps per 100 µL with a positive displacement-pipette on the top of the BIOBARRIER disc and starting time was recorded with the first 100 µL. The total application has taken 30 seconds. This step was repeated for the remaining vials, staggering each start time by e.g. 10 seconds. The start time difference for each vial was subtracted from the final time to determine the net response time. As soon as a reaction had been observed, the time was recorded.

Control samples:

other: Negative control: 10% citirc acid, positive control: 85% phosphoric acid

Amount/concentration applied:

0.5 mL

Duration of treatment / exposure:

min. 240 minutes

Duration of post-treatment incubation (if applicable):

n.a.

Number of replicates:

4

Amount / concentration applied:

TEST SYSTEM
- Bio-barrier membrane

TEST MATERIAL
- Amount applied: 500 µL

Observation period:

4 hours

Details on study design:

This assay is composed of three different steps:

1. Qualification
This step ensures that the sample is compatible with the CORROSITEX™ system. 150 µL of the test substance are added to the Qualify test tube. Solids are shaken to dissolve, if necessary. For immiscible liquids and insoluble solids the vial is shaken and let stand for one minute. If the colour or consistency of the CDS changes at the sample/testing fluid interface, the test material is qualified for the assay. If no reaction is observed within five minutes, the sample is not qualified for the CORROSITEX™ Assay.

2. Categorisation
This step establishes the category for cut-off times for the sample. 150 µL of the test substance are added to the tubes labeled Tube A and Tube B. After shaking a colour change in either of the tubes is matched to the corresponding colour charts on the CORROSITEX™ Testing Protocol Poster. Test materials having high acid/alkaline reserves are defined as Category 1 materials, while those with low acid/alkaline reserves are defined as Category 2 materials. If no colour change is observed in either tube, CONFIRM reagent is added to Tube B. After shaking, the resulting colour is matched to the colour chart on the CORROSITEX™ Testing Protocol Poster.
If the test item has strong colouring or shows other characteristics impairing a clear categorization according to the colour chart, the pH value can be measured in the tubes A and B and is used to confirm/determine the category of the test item

3. Classification
This step determines the appropriate Packing Group for the test sample. The CDS vials are warmed to room temperature (17 - 25˚C) before using. Vials 1 - 4 are utilized for sample replicate testing. Controls are set-up in parallel to the test item in order to confirm the validity of the test: positive control, negative control and one colour control. One BIOBARRIER disc was added on top of the first vial. 500 µL of the test item were applied by five steps per 100 µL with a positive displacement-pipette on the top of the BIOBARRIER disc and starting time was recorded with the first 100 µL. This step was repeated for the remaining vials, staggering each start time by e.g. 10 seconds. The start time difference for each vial was subtracted from the final time to determine the net response time. As soon as a reaction had been observed, the time was recorded.

Irritation / corrosion parameter:

penetration time (in minutes)

Run / experiment:

mean of 4 replicates

Value:

20.92

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

positive indication of irritation

Qualification Test / Categorization Test

The test substance was compatible with the CORROSITEX™ Assay, as assessed in the qualification step. A direct colour change was observed in tube A and the category was read from the CORROSITEX™ colour chart. The chemical has been categorized to category 1.

Classification Test

	CORROSITEX™ time [min]	Colour change	consistency change
Replicate 1	20.17	yes	no
Replicate 2	20.75	yes	no
Replicate 3	21.17	yes	no
Replicate 4	21.58	yes	no
Mean +/- SD	20.92 +/- 0.60
Positive Control	12.33	yes	no
Negative Control	88.78	yes	no

The mean time, required to activate the CDS was 20.92 +/- 0.60 min.

 

Interpretation of results:

Category 1B (corrosive)

Remarks:

Migrated information Criteria used for interpretation of results: other: OECD 435

Conclusions:

In this study under the given conditions the test substance showed corrosive effects. The test substance is classified as “CORROSIVE”, subcategory 1B according to the UN GHS, as the mean time to activate the CDS was > 3 – 60 min, (category 1). The test substance is therefore assigned to Packing Group 2 and to EU Risk-Phrase (R 34).

Executive summary:

The potential of the test substance to induce skin corrosion was analysed by using the “In Vitro Membrane Barrier Test (CORROSITEX™ Assay)”, comprising a Chemical Detection System covered by a bio-barrier membrane.

The test substance Hordaphos CC MIN proved its ability to activate the CDS and was subsequently subjected to the timescale category test. The test substance was applied undiluted atop thebio-barrier membraneand the timerequired to activate the CDS was measured in four replicates. The mean time was compared to the given thresholds (see Table 1).

The test substance was compatible with the CORROSITEX™ Assay, as assessed in the qualification step. The categorization step and the classification step could be performed.

A direct colour change was observed in tube A and the category was read from the CORROSITEX™ colour chart. The chemical has been categorized to category 1.

In this study under the given conditions the test substance showed corrosive effects. The test substance is classified as “CORROSIVE”, subcategory 1B according to the UN GHS, as the mean time to activate the CDS was > 3 – 60 min, (20.92 ± 0.60 min.) (category 1). The test substance is therefore assigned to Packing Group 2 and to EU Risk-Phrase (R 34).

The controls confirmed the validity of the study. The test substance qualified for the CORROSITEX™ Assay, as assessed in the qualification test. The positive control activated the CDS between 3 - 60 min. (12.33 min.), the negative control did not activate the CDS before 60 min. (88.78 min.).

This study satisfies the requirement for Test Guideline OECD 435 for in vitro Membrane Barrier Test Method for Skin Corrosion.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study need not be conducted because the available information indicates that the criteria are met for classification as corrosive to the skin or irritating to eyes

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

With reference to the presence of bloody, scabby skin after application to rabbit skin the registration substance has to be classified as corrosive to the skin, Cat. 1 (H314 – Causes severe skin burns and eye damage) according to the criteria laid down in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).

It is concluded that the undiluted registration substance has to be classified as irritant to the eyes (H318 - Causes serious eye damage) according to the criteria laid down in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).