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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:
26 Jan - 16 Feb 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

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

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adpoted May 1981
Deviations:
yes
Remarks:
limited documentation
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 2-Dimethylamino-2-methyl-1-propanol, 73% DMAMP, Polymeen A (P-2614)
- Substance type: clear, pale yellow liquid
- Analytical purity: 72.03%
- Lot/batch No.: 730H18DF36
- pH: 12.5

Test animals / tissue source

Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.6 kg (mean in undiluted and 50% treatment group), 2.5 kg (mean in 25% treatment group)

Test system

Vehicle:
water
Controls:
other: the untreated eye served as the control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): 25% dilution, 50% dilution and undiluted (of a 72.03% solution)

VEHICLE
- Concentration (if solution): 75 and 50%
Duration of treatment / exposure:
25 % dilution and undiluted: single application without washing or removal of test substance 20-30 seconds after instillation
50% dilution: single application without washing
Observation period (in vivo):
21 days
Reading time points: 24, 48 and 72 h, and 4, 7, 14 and 21 days
Number of animals or in vitro replicates:
Undiluted: 9 (6 with unwashed and 3 with washed eyes)
50% dilution: 3 (unwashed eyes only)
25% dilution: 9 (6 with unwashed and 3 with washed eyes)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): for 3 rabbits in each of the groups exposed to a 25% solution and undiluted test substance, the eyes were rinsed with 50 mL lukewarm tap water 20 - 30 seconds after instillation. The eyes of the remaining rabbits were not washed.
- Time after start of exposure: 20 - 30 seconds

SCORING SYSTEM: Draize scoring system. The eyes were examined 24, 48 and 72 hours, and 4, 7, 14 and 21 days after treatment.

TOOL USED TO ASSESS SCORE: fluorescein

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
other: washed eye, undiluted substance
Irritation parameter:
iris score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
24/48/72 h
Score:
1.33
Max. score:
2
Reversibility:
not fully reversible within: 21 days
Remarks on result:
other: washed eye, undiluted substance
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
24/48/72 h
Score:
2.76
Max. score:
3
Reversibility:
fully reversible within: 21 days
Remarks on result:
other: washed eye, undiluted substance
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
24/48/72 h
Score:
3.19
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: washed eye, undiluted substance
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
24/48/72 h
Score:
1.34
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
other: washed eye, 25% dilution
Irritation parameter:
iris score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 21 days
Remarks on result:
other: washed eye, 25% dilution
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
24/48/72 h
Score:
1.89
Max. score:
3
Reversibility:
fully reversible within: 21 days
Remarks on result:
other: washed eye, 25% dilution
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
24/48/72 h
Score:
1.69
Max. score:
4
Reversibility:
fully reversible within: 21 days
Remarks on result:
other: washed eye, 25% dilution
Irritant / corrosive response data:
Undiluted: Immediately after instillation of the test material, the rabbits vocalized, indicating severe eye irritation. At the 24 h time point, the unwashed and washed eyes in all the rabbits showed severe eye irritation with corneal lesions. The severity was only slightly reduced by the 72 h time point. In rabbits with both unwashed and washed eyes the corneal opacity and corneal lesions were still visible by fluorescein treatment on day 7. The corneas were keratinised in all the animals after day 7, a condition which is irreversible. One animal with unwashed and one with washed eyes was sacrificed on day 7 due to the severe eye damage (see Table 1).

The pH of the undiluted liquid is 12.5, which means that the effect of the test substance is most probably due to the high alkalinity. This is also indicated by the severe eye damage that even the 25% dilution caused.

50% dilution: The eyes of the three rabbits showed severe eye irritation from the 24 h time point, with lesions on the cornea. The severity was only slightly reduced by the 72 h time point. The eyes were keratinised after day 14, a condition which is irreversible. One animal was sacrificed on day 14 and one by day 21 due to the severe eye damage.

25% dilution: The eyes of the rabbits in the unwashed and washed group showed severe eye irritation and corneal lesions when examined after 24 hours. The eyes of all the rabbits were keratitised after day 14, with the exception of one animal in the washed eye group, where the effects were almost or completely reversed by day 21. Of the rabbits with unwashed eyes, 4 were sacrificed on day 14 due to the severity of the damage.
Other effects:
There was no effect on body weight.

Any other information on results incl. tables

Table 1. Individual scores for rabbit eyes instilled with undiluted test substance and washed

Rabbit #

 

Time [h]

 

conjunctivae

 

iris

 

cornea

 

redness

swelling

1

 

 

 

 

24

3

4

2

3

48

3*

3.3*

1.3*

2*

72

2.3*

2.6*

1.3*

2*

average

2.77

3.3

1.53

2.33

2

 

 

 

 

24

3

4

1

2

48

3*

3.3*

1.3*

2*

72

2.3*

2.6*

1.3*

2*

average

2.77

3.3

1.2

2

3

 

 

 

 

24

3

3

1

1

48

3*

3.3*

1.3*

2*

72

2.3*

2.6*

1.3*

2*

Average

2.77

2.97

1.2

1.67

* for the 48 and 72-hour reading time points only average scores were reported

 

 

 

 

 

Average score

Time [h]

Conjunctivae

Iris

Cornea

Redness

Swelling

24 h

2.77

3.3

1.53

2.33

48 h

2.77

3.3

1.2

2

72 h

2.77

2.97

1.2

1.67

24+48+72

2.77

3.19

1.31

2

* for the 48 and 72-hour reading time points only an average score of the 3 animals was reported

Applicant's summary and conclusion

Interpretation of results:
corrosive
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: Eye corrosion 1, H318
DSD: Xi, R41