Reaction mass of methyl dihydrogen phosphate and orthophosphoric acid and dimethyl hydrogen phosphate

Endpoint summary

Description of key information

There are two studies available on the skin irritancy potential. A 1:10 dilution of Reaction mass of Methyl dihydrogen phosphate and Orthophosphoric acid and Dimethyl hydrogen phosphate was tested for its skin irritant properties in 3 or 5 Yellow-silver strain rabbits. The study was similar to OECD Guideline 404. Effects on the skin (necrosis and scrabby skin) were observed all animals after application. Therefore, it is concluded that the undiluted reaction mass of Methyl dihydrogen phosphate and Orthophosphoric acid and Dimethyl hydrogen phosphate is corrosive.
There are two studies available on the eye irritancy potential. A 1:20 dilution of Reaction mass of Methyl dihydrogen phosphoric phosphate and Orthophosphoric acid and Dimethyl hydrogen phosphate was tested for its eye irritant properties in 3 or 5 Yellow-silver strain rabbits. The study was similar to OECD Guideline 405. 
The application of a 1:10 dilution of the test substance to the eyes of 3 rabbits lead to moderate opacity, slight reddening and swelling of the conjunctivae. 

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:

weight of evidence

Study period:

April 1968

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Study design follows the "Barail-Test"; summary report

Qualifier:

equivalent or similar to guideline

Guideline:

other: Barail Test

Deviations:

not specified

Principles of method if other than guideline:

The test substance was applied in dilutions (1:10 and 1:30) to rabbit`s skin on 5 consecutive days.

GLP compliance:

no

Remarks:

performed before GLP

Species:

rabbit

Strain:

other: Yellow-silver strain

Details on test animals or test system and environmental conditions:

TEST ANIMAL
- Housing: individually
- Diet (e.g. ad libitum): Standard Altromin K (Altrogge, Lage/Lippe, Germany), ad libitum
- Water (e.g. ad libitum): tap water, ad libitum

Type of coverage:

not specified

Preparation of test site:

clipped

Vehicle:

physiological saline

Controls:

not required

Amount / concentration applied:

0.5 mL of 1:10 or 1:30 dilution

Duration of treatment / exposure:

once every day on 5 consecutive days

Observation period:

5 days

Number of animals:

5

Details on study design:

no data

Irritation parameter:

erythema score

Remarks:

only description of skin reaction available; non guideline study

Basis:

mean

Time point:

24/48/72 h

Max. score:

4

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Remarks:

only description of skin reaction available; non guideline study

Basis:

mean

Time point:

24/48/72 h

Max. score:

4

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

1:10 dilution: slightly reddened, scrabby skin
1:30 dilution: no effects

Observed effects:

1:10 dilution: slightly reddened, scrabby skin

1:30 dilution: no effects

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

The application of a 1:10 dilution the test substance on 5 consecutive days to the clipped skin of 5 rabbits lead to slightly reddened scrabby skin. Therefore, it is concluded that the undiluted reaction mass of Methyl dihydrogen phosphate and Orthophosphoric acid and Dimethyl hydrogen phosphate is irritant at least.

Executive summary:

The test substance was applied in dilutions (1:10 and 1:30) to rabbit`s skin on 5 consecutive days. The 1:10 dilution lead to skin reddened scrabby skin. No effects were observed after the repeated application of the 1:30 dilution.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

Apr 1968

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Study design similar to OECD Guideline with some deviations; summary report

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

dilutions tested

GLP compliance:

no

Remarks:

performed before GLP

Species:

rabbit

Strain:

other: Yellow-silver strain

Details on test animals or tissues and environmental conditions:

TEST ANIMAL
- Housing: individually
- Diet (e.g. ad libitum): Standard Altromin K (Altrogge, Lage/Lippe, Germany), ad libitum
- Water (e.g. ad libitum): tap water, ad libitum

Vehicle:

physiological saline

Controls:

not required

Amount / concentration applied:

0.1 mL of 1:10 or 1:100 dilution

Duration of treatment / exposure:

The eyes were not washed after application.

Observation period (in vivo):

1 hour post application
3 hour post application
7 hour post application
24 hours post application
48 hours post application
72 hours post application

Number of animals or in vitro replicates:

5

Details on study design:

After treatment the eyes were not washed out.

Irritation parameter:

cornea opacity score

Remarks:

only qualitiative description of the effects in the eye available, non guideline study

Basis:

mean

Time point:

24/48/72 h

Max. score:

4

Reversibility:

not specified

Remarks on result:

probability of severe irritation

Irritation parameter:

iris score

Remarks:

only qualitiative description of the effects in the eye available, non guideline study

Basis:

mean

Time point:

24/48/72 h

Max. score:

2

Reversibility:

not specified

Remarks on result:

probability of severe irritation

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Max. score:

3

Reversibility:

not specified

Remarks on result:

probability of severe irritation

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Max. score:

4

Reversibility:

not specified

Remarks on result:

not determinable

Irritant / corrosive response data:

- 1:10 dilution:
eye slightly reddened, moderate opacity and swelling of the conjunctivae

- 1:100 dilution:
eye slightly reddened; effects reversible within 1h

Other effects:

no further data

Observed effects:

- 1:10 dilution:

eye slightly reddened, moderate opacity and swelling of the conjunctivae

- 1:100 dilution:

eye slightly reddened; effects reversible within 1h

Interpretation of results:

corrosive

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

The application of a 1:10 dilution of the test substance to the eyes of 5 rabbits lead to moderate opacity, reddening and swelling of the conjunctivae.
Therefore it is concluded that the undiluted reaction mass of Methyl dihydrogen phosphate and Orthophosphoric acid and Dimethyl hydrogen phosphate has to be classified as irritant to the eyes (R41 - Risk of serious damage to the eyes; H318 - Causes serious eye damage) according to the criteria laid down in the EU Dangerous Substances Directive (67/548/EEC) and in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).

Executive summary:

A 1:10 and 1:100 dilution of reaction mass of Methyl dihydrogen phosphateand Orthophosphoric acid and Dimethyl hydrogen phosphate were tested for its eye irritant properties in 5 rabbits.The study was performed similar to OECD Guideline 405.

The application of a 1:10 dilution of the test substance to the eyes of 3 rabbits lead to moderate opacity, slight reddening and swelling of the conjunctivae.

Therefore it is concluded that the undiluted reaction mass of Methyl dihydrogen phosphate and Orthophosphoric acid and Dimethyl hydrogen phosphate has to be classified as irritant to the eyes (R41 - Risk of serious damage to the eyes; H318 - Causes serious eye damage) according to the criteria laid down in the EU Dangerous Substances Directive (67/548/EEC) and in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation: 2 studies available: corrosive; 1 read across available: corrosive

Eye irritation: 2 studies available: corrosive

 

There are two studies available on the skin irritancy potential. A 1:10 dilution of Reaction mass of Methyl dihydrogen phosphate and Orthophosphoric acid and Dimethyl hydrogen phosphate was tested for its skin irritant properties in 3 or 5 Yellow-silver strain rabbits. The study was similar to OECD Guideline 404. Effects on the skin (necrosis and scrabby skin) were observed all animals after application. Therefore, it is concluded that the undiluted reaction mass of Methyl dihydrogen phosphate and Orthophosphoric acid and Dimethyl hydrogen phosphate is corrosive.
In another skin irritation study performed with Phosphoric acid, butyl ester which was taken for read across purposes, the substance was applied to the clipped skin of one White Russian rabbit. Effects on the skin (erythema grades up to 4 and edema scores up to 4 as well as necrosis) were observed 1 hour after application.These signs were not reversible within 14 days.
The substance tested in the present skin irritation study, Phosphoric acid, butyl ester, and the substance to be registered, Reaction mass of Methyl dihydrogen phosphate and Orthophosphoric acid and Dimethyl hydrogen phosphate are both members of the Phosphoric acid, alkyl ester family. The characteristic and active functionalities of this substance category are the central ester binding and the free hydroxyl group(s) for which most of the Phosphoric acid, alkyl esters are proven to be corrosive. Both Phosphoric esters have a very low pKa (Reaction mass of Methyl dihydrogen phosphate: 2.6 (first step); Phosphoric acid, butyl ester: 2.5 (first step)) value indicating the strong tendency to set free protons, which themselves are responsible for the pH and consequently for the skin/eye corrosive properties of the short chain Phosphoric acid, alkyl esters. Since the Reaction mass of Methyl dihydrogen phosphoric phosphate and Orthophosphoric acid and Dimethyl hydrogen phosphate takes over an intermediate role between Orthophosphoric acid and Phosphoric acid, butyl ester (both corrosive) with reference to its physical-chemical and structural properties a read across between Phosphoric acid, butyl ester and Phosphoric acid, methyl ester is supposed to be justified.

With reference the reported scores and the presence of necrotic skin Reaction mass of Methyl dihydrogen phosphoric phosphate and Orthophosphoric acid and Dimethyl hydrogen phosphate has to be classified as corrosive to the skin (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).

There are two studies available on the eye irritancy potential. A 1:20 dilution of Reaction mass of Methyl dihydrogen phosphoric phosphate and Orthophosphoric acid and Dimethyl hydrogen phosphate was tested for its eye irritant properties in 3 or 5 Yellow-silver strain rabbits. The study was similar to OECD Guideline 405.

The application of a 1:10 dilution of the test substance to the eyes of 3 rabbits lead to moderate opacity, slight reddening and swelling of the conjunctivae.

 

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Justification for classification or non-classification

With reference the reported scores and the presence of necrotic skin Reaction mass of Methyl dihydrogen phosphoric phosphate and Orthophosphoric acid and Dimethyl hydrogen phosphate has to be classified as corrosive to the skin (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 reaction mass of Methyl dihydrogen phosphate and Orthophosphoric acid and Dimethyl hydrogen phosphate has to be classified as irritant to the eyes (R41 - Risk of serious damage to the eyes; H318 - Causes serious eye damage) according to the criteria laid down in the EU Dangerous Substances Directive (67/548/EEC) and in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).