Hydrogen bis[2-[(4,5-dihydro-3-methyl-5-oxo-1-phenyl-1H-pyrazol-4-yl)azo]benzoato(2-)]chromate(1-), compound with 2-ethylhexylamine (1:1)

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: early study with short report but giving the essential details of the experiment; no GLP, poor substance characterisation

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1975

Report date:

1975

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

6 animals used

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: Code of Federal Regulations, Title 16, Section 1500.42

GLP compliance:

no

Remarks:

pre-dates GLP regulation

Test material

Test material information

Constituent 1

Reference substance name:

Hydrogen bis[2-[(4,5-dihydro-3-methyl-5-oxo-1-phenyl-1H-pyrazol-4-yl)azo]benzoato(2-)]chromate(1-), compound with 2-ethylhexylamine (1:1)

EC Number:

275-864-7

EC Name:

Hydrogen bis[2-[(4,5-dihydro-3-methyl-5-oxo-1-phenyl-1H-pyrazol-4-yl)azo]benzoato(2-)]chromate(1-), compound with 2-ethylhexylamine (1:1)

Cas Number:

71701-15-0

Molecular formula:

C42H44CrN9O6

IUPAC Name:

Chromate(1-), bis[2-[2-[4,5-dihydro-3-methyl-5-(oxo-kO)-1-phenyl-1H-pyrazol-4-yl]diazenyl-kN1]benzoato(2-)-kO]-, hydrogen, compd. with 2-ethyl-1-hexanamine (1:1:1)

Test animals / tissue source

Species:

rabbit

Strain:

not specified

Details on test animals or tissues and environmental conditions:

no data

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

100 µL = 53 mg

Duration of treatment / exposure:

24 hours, no washing

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

6

Details on study design:

Six albino rabbits are used for each test substance.
Animal facilities for such procedures shall be so designed and maintained as to exclude sawdust, wood chips, or other extraneous materials that might produce eye irritation. Both eyes of each animal in the test group shall be examined before testing, and only those animals without eye defects or irritation shall be used. The animal is held firmly but gently until quiet. The test material is placed in one eye of each animal by gently pulling the lower lid away from the eyeball to form a cup into which the test substance is dropped, The Iids are then gently held together for one second and the animal is released.
The other eye, remaining untreated, serves as a control. For testing liquids, 0.1 mL is used. For solids or pastes, 100 milligram of the test substance is used, except that for substances in flake, granule, powder, or other particulate form the amount that has a volume of 0. l millilitre (after compacting as much as possible without crushing or altering the individual particles, such as by tapping the measuring container) shall be used whenever this volume weighs less than 100 milligram. In such a case, the weight of the 0. 1 mL test dose should be recorded. The eyes are not washed following instillation of test material except as noted below:
The eyes are examined and the grade of ocular reaction is recorded at 24, 48 and 72 hours. Reading of reaction is facilitated by use of a binocular Ioupe, hand slit-lamp, or other expert means.
After the recording of observations at 24 hours, any or all eyes may be further examined after applying fluorescein. For this optional test, one drop of fluorescein sodium ophthalmic solution U.S.P. or equivalent is dropped directly on the cornea. After flushing out the excess fluorescein with sodium chloride solution U.S.P. or equivalent, injured areas of the cornea appear yellow; this is best visualized in a darkened room under ultra-violet illumination. Any or all eyes may be washed with sodium chloride solution U.S. P. or equivalent after the 24 hour reading.
An animal shall be considered as exhibiting a positive reaction if the test substance produces at any of the readings ulceration of the cornea (other than a fine stippling), or opacity of the cornea (other than a slight dulling of the normal lustre), or inflammation of the iris (other than a slight deepening of the folds (or rugae) or a slight circumcorneal injection of the blood vessels), or if such substance produces in the conjunctivae (excluding the cornea and iris) an obvious swelling with partial eversion of the lids or a diffuse crimson-red with individual vessels not easily discernible.
The test shall be considered positive if four or more of the animals in the test group exhibit a positive reaction. If only one animal exhibits a positive reaction, the test shall be regarded as negative. If two or three animals exhibit a positive reaction, the test is repeated using a different group of six animals. The second test shall be considered positive if three or more of the animals exhibit a positive reaction. If only one or two animals in the second test exhibit a positive reaction, the test shall be repeated with a different group of six animals. Should a third test be needed, the substance will be regarded as an irritant if any animal exhibits a positive response.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24 h

Score:

0

Max. score:

0

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24 h

Score:

0

Max. score:

0

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24 h

Score:

1.66

Max. score:

2

Reversibility:

not fully reversible within:

Remarks on result:

other: 1 of 6 animals showed a slight redness on day7

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 3 days

Results 5

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 24 h to 72 h

Score:

1.1

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: 1 of 6 animals showed a slight redness on day7

Irritant / corrosive response data:

none to slight redness and swelling in 3 of 6 animals.

Other effects:

no data

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test item is considered to be "non-irritant" to the rabbit eye when classified as recommended by the ETAD Sub-committee for Toxicology.

Executive summary:

EXPERIMENTAL PROCEDURE

The procedure employed was that prescribed by The Consumer Product Safety Commission of the U.S.A. in The Code of Federal Regulations, Title 16, Section 1500.42.

On this occasion 53 mg of the test item was instilled into one eye of each animal, the other eye remaining untreated, served as control. The ocular reactions were scored by the method described by J.H. Draize in "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" p51, 1959 and categorized from the mean values as recommended by the ETAD Sub-committee .for Toxicology.

RESULT

A diffuse crimson red colouration of the conjunctivae was observed in one animal.

Mild conjunctival reactions were observed in two animals.

Three animals did not show any observable response to treatment throughout the 7 days observation period.

Mean Draize score at days 1, 2 and 3 = 1.1

CONCLUSION Savinylgelb RLS is considered to be "non-irritant" to the rabbit eye when classified as recommended by the ETAD Sub-committee for Toxicology.