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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
7. Oct - 21. Oct 1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline conform study with sufficient reporting.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
clear liquid
densitiy: ca. 1130 kg/m3
melting point: < -10°C

Test animals

Species:
rabbit
Strain:
other: white Russian
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dr. Karl Thomae GmbH, Biberach, Germany
- Weight at study initiation: 2,3 kg
- Housing: individually in stainless seel cages
- Diet (e.g. ad libitum): K4 Alleindiät für Kaninchen (Sniff Spezialfutter GmbH, Soest, Germany), ad libitum
- Water (e.g. ad libitum): tap water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 1°C
- Humidity (%): 60 +/-5%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12

IN-LIFE DATES: From: 07.10. To: 21.10.1986

Test system

Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
4 h
Observation period:
a. 60 min post applicationem
b. 24 h post applicationem
c. 48 h post applicationem
d. 72 h post applicationem
e. 6 d post applicationem
f .8 d post applicationem
g .10 d post applicationem
h .14 d post applicationem
Number of animals:
1; no further testing mandatory since the substance is corrosive
Details on study design:
TEST SITE
- Area of exposure: 6 cm2
- % coverage: 100%
- Type of wrap if used: The treated area was covered with a gauze patch to prevent loss of test material. The test material and the gauze patch were covered with polyethylene foil and held in contact with the skin with a semi-occlusive patch adhesive tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the residual test substance was removed with warm water
- Time after start of exposure: 4 h

SCORING SYSTEM:
Erythema and eschar formation
No erythema.......................................................................................................................0
very slight erythema (barely perceptible)......................................................................1
well-defined erythema......................................................................................................2
moderate to severe erythema..........................................................................................3
severe erythema (beet redness) to slight eschar formation (lesion in depth).........4

Oedema
No oedema...................................................................................................................................0
very slight oedema (barely perceptible)..................................................................................1
slight oedema (edges of area well defined by definite raising)............................................2
moderate oedema (raised approximately 1mm)....................................................................3
severe oedema (raised more than 1mm and extending beyond area of exposure.........4

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
mean
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
mean
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritant / corrosive response data:
Necrosis was reported from 1 h after application until study termination
Other effects:
no other effects reported

Applicant's summary and conclusion

Interpretation of results:
corrosive
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The strucutral analogon, Phosphoric acid, butyl ester, was tested for its skin irritant properties in 1 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.Therefore, the reaction mass of Methyl dihydrogen phosphate and Orthophoshoric acid and Dimethyl hydrogen phosphate is considered to have to be classified as corrosive to the skin (Causes severe skin burns and eye damage - H314) according to the criteria laid down in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).
Executive summary:

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.

Phosphoric acid, butyl ester was tested for its skin irritant properties in 1 White Russian rabbit. The study was performed according to OECD Guideline 404. 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.

Therefore, the reaction mass of Methyl dihydrogen phosphate and Orthophoshoric acid and Dimethyl hydrogen phosphate is considered to have to be classified as corrosive to the skin (Causes severe skin burns and eye damage - H314) according to the criteria laid down in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).