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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
9 December 1981 – 16 December 1981
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study, to GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
see below
Principles of method if other than guideline:
In one group of animals the eye remained unwashed and in the other group the eye was washed 30 seconds after instillation of the test material. The guideline states that “the eyes of the test animals should not be washed for at least 24 hours following instillation of the test substance, except for solids, and in case of immediate corrosive or irritating effects. At 24 hours a washout may be used if considered appropriate.” It goes on to say, in the case of solids, that “if the solid test substance has not been removed from the eye of the test animal by physiological mechanisms at the first observation time point of 1 hour after treatment, the eye may be rinsed with saline or distilled water.” The guideline strongly recommends that “the in vivo test be performed initially using one animal” and if the result indicates a corrosive or severe irritant effect further testing should not be performed. This study used test groups of 3 animals. The animals were examined 7 days after treatment to assess the reversibility of the effects however the guideline states that “to determine reversibility of effects, the animals should be observed normally for 21 days post administration”.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): potassium tetrachloroplatinate (II)
- Molecular formula (if other than submission substance): K2PtCl4
- Substance type: orange-brown powder
- Physical state: solid
- Lot/batch No.: 031440A

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Nottingham University, School of Agriculture, Sutton Bonington, Leicestershire
- Weight at study initiation: 2.08-2.42 kg
- Housing: individually in suspended metal cages
- Diet: ad libitum rabbit diet supplied by J. Waring Limited, Shardlow, Derbyshire
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Air changes (per hr): a minimum of 20 /hr
- Photoperiod (hrs dark / hrs light): lighting cycle of 12 hrs on, 12 hrs off with no daylight

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: Yes, untreated eye
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg
Duration of treatment / exposure:
“Unwashed group” - Eye not rinsed, therefore possibly up to 7 days
“Washed group” - 30 seconds
Observation period (in vivo):
1, 24, 48 and 72 hrs after application and, if irritation persisted, an additional reading was made at day 7 to assess reversibility or irreversibility.
Number of animals or in vitro replicates:
6 (3/group), sex not specified
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, in one of the groups
- Time after start of exposure: 30 seconds

SCORING SYSTEM: Assessment of damage/irritation in both the washed and unwashed groups was made 1, 24, 48 and 72 hr following instillation of the test material, according to the numerical evaluation of Draize (1965). The test material was then assigned a Group Total Score for Eye Irritation.

TOOL USED TO ASSESS SCORE: standard ophthalmoscope (Keeler). The degree of irritation was further investigated at 24 hr under ultra-violet illumination (Mineralight UVSL-58) preceded by the instillation into the eye of fluorescein B.P.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
overall irritation score
Basis:
other: Group Total Score, unwashed group
Time point:
other: 1, 24, 48, 72 hrs and 7 days
Score:
ca. 99
Max. score:
195
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
other: Total score, unwashed group
Time point:
other: 1, 24, 48, 72 hrs and 7 days
Score:
ca. 10
Max. score:
60
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: See below - (1)
Irritation parameter:
iris score
Basis:
other: Total score, unwashed group
Time point:
other: 1, 24, 48, 72 hrs and 7 days
Score:
ca. 13
Max. score:
30
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: See below - (2)
Irritation parameter:
other: conjunctivae score (redness)
Basis:
other: Total score, unwashed group
Time point:
other: 1, 24, 48 and 72 hrs and 7 days
Score:
ca. 31
Max. score:
45
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: See below - (3)
Irritation parameter:
other: conjunctivae score (chemosis)
Basis:
other: Total score, unwashed group
Time point:
other: 1, 24, 48 and 72 hrs and 7 days
Score:
ca. 45
Max. score:
60
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: See below - (4)
Irritation parameter:
overall irritation score
Basis:
other: Group Total Score, washed group
Time point:
other: 1, 24, 48, 72 hrs and 7 days
Score:
ca. 82
Max. score:
195
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
other: Total score, washed group
Time point:
other: 1, 24, 48, 72 hrs and 7 days
Score:
ca. 2
Max. score:
60
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: See below - (5)
Irritation parameter:
iris score
Basis:
other: Total score, washed group
Time point:
other: 1, 24, 48, 72 hrs and 7 days
Score:
ca. 9
Max. score:
30
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: see below - (6)
Irritation parameter:
other: conjunctivae score (redness)
Basis:
other: Total score, washed group
Time point:
other: 1, 24, 48 and 72 hrs and 7 days
Score:
ca. 32
Max. score:
45
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: See below - (7)
Irritation parameter:
other: conjunctivae score (chemosis)
Basis:
other: Total score, washed group
Time point:
other: 1, 24, 48 and 72 hrs and 7 days
Score:
ca. 39
Max. score:
60
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: See below - (8)
Irritant / corrosive response data:
(1) Slight diffuse corneal opacity was seen in all of the treated animals after 24 hrs. Reversibility was only noted in one of the three rabbits at the 72 hr observation period, however there was no improvement in the degree of irritation in the remaining two rabbits at up to 7 days.

(2) Iridial congestion was noted in all of the treated animals after 1 hr. Reversibility was seen in only one of the three rabbits at the 72 hr observation period, and there was no improvement in the degree of irritation in the remaining two rabbit at up to 7 days.

(3) One hr following treatment, slight to diffuse crimson redness was seen in the conjunctival palpebra of all of the treated rabbits, the effect being more marked at the 24 hr observation time with diffuse beefy redness of the palpebra being apparent in two of the three animals. After 48 and 72 hrs, one rabbit showed a slight improvement and another a significant improvement in the irritation, whereas no improvement was seen in the third. The effect was completely reversible by the 7 day observation period in only one of the animals.

(4) Slight to moderate chemosis was seen in all of the treated animals after 1 hr, with the effect becoming more marked after 24 hrs and all animals showing severe chemosis with the lids more than half closed. A slight improvement was seen in one rabbit after 48 hrs and in another after 72 hrs but no improvement was seen in the third animal. The effect had completely disappeared in only one of the three rabbits by the 7 day observation period.

(5) Slight, diffuse corneal opacity was seen in one of the three rabbits at the 24 and 48 hr observation times and the effect had totally disappeared 72 hrs after treatment.

(6) Iridial congestion was seen 1 hr after treatment in all of the treated animals. The irritation became less marked as the observation period proceeded and complete recovery was noted in all of the rabbits after 7 days.

(7) Redness of the conjunctival palpebra was noted in all of the treated rabbits 1 hr after instillation and became a diffuse beefy redness after 24 hrs in two of the animals. Slight recovery was seen in these two animals after 48 hrs but the irritation persisted throughout the entire 7 day observation period.

(8) Slight to moderate chemosis was noted in all of the treated animals after 1 hr, with severe chemosis being recorded in 2 of the rabbits at 24 hrs. The effect had become more marked in the third animal. By 48 hrs, the irritation in the two animals had improved slightly but no further improvement was seen in any of the animals up to the 7 day observation time.

The test material produced moderate ocular irritation in all of the treated rabbits when the eye remained unwashed or was washed after 30 seconds. Irritant effects were recorded in the cornea, iris and conjunctiva. In the unwashed group, only one of the three rabbits showed evidence of complete reversibility after 7 days, the other two showing no improvement in the degree of irritation between the 72 hr and 7 day observation times. When the eye was washed, all evidence of corneal and iridial irritation had disappeared by the 72 hr and 7 day readings respectively. Conjunctival redness and chemosis persisted throughout the 7 day recovery period.

Other effects:
No data

Applicant's summary and conclusion

Interpretation of results:
Category I
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In a guideline eye irritation study, potassium tetrachloroplatinate (II) (0.1 g) produced a group total score of 99 following application into the eye of three rabbits, when the eye was left unwashed. When the test material was washed from the eye 30 seconds following instillation into the eye of a further three rabbits, a group total score of 82 was produced. The observed irritation was not reversible within the 7-day observation period in either group.
Executive summary:

In an OECD Test Guideline 405 study, potassium tetrachloroplatinate (II) (0.1 g) was instilled into the conjunctival sac of the right eye of six rabbits and both lids were briefly closed for about 1 second. The other eye remained untreated and acted as the control. In half of the animals, the treated eye was irrigated with 100 ml sterile distilled water, 30 seconds following instillation. Assessment of damage/irritation to the cornea, iris and conjunctiva of the treated eye, using the Draize scale, was made 1, 24, 48 and 72 hrs following treatment. If irritation was persistent at 72 hrs, an additional reading was made on day 7 in order to assess the reversibility of the effects. These scores were then combined to give a Group Total Score for Eye Irritation of 99 (out of 195) for the unwashed eye and 82 (out of 195) for the washed eye. In both groups, the effects were not reversible within the 7-day period.

 

Based on the results of this study, potassium tetrachloroplatinate (II) should be classified as Category 1 (irreversible effects on the eye) according to EU CLP criteria (EC 1272/2008).