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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study according to OECD Guideline 405 (adopted 1981).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
2,2-Dimethyl-1,3-propanediol

Test animals / tissue source

Species:
rabbit
Strain:
other: Small White Russian
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Fa . Dr . Karl Thomae GmbH, Biberach, FRG
- Age at study initiation: no data
- Weight at study initiation: 2.1-2.5 kg
- Housing: individually
- Diet (ad libitum): K4 for rabbits, Ssniff Spezialfutter GmbH, Soest, FRG
- Water (ad libitum): tap water
- Acclimation period: 14 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21
- Humidity (%): 55-65
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: right eye no treatment
Amount / concentration applied:
0.1 ml or ca. 100 mg test substance (solid) instilled into the conjunctival sac.
Duration of treatment / exposure:
no washing
Observation period (in vivo):
Scoring 1, 24, 48, and 72 hours and 6, 8, 10, 13, 17, and 21 days after instillation.
Number of animals or in vitro replicates:
3 males and 3 females
Details on study design:
Scoring system according to OECD Guideline 405; additionally the area of the cornea involved concerning opacity was determined and scored as described in the Table below. The same was done with discharge from conjunctivae (see Table below).

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24 h
Score:
1.16
Max. score:
4
Reversibility:
not fully reversible within: within 21 days
Remarks on result:
other: irreversible damage; in 2 out of 6 rabbits corneal opacity score 2
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 72 h
Score:
0.83
Max. score:
2
Reversibility:
not fully reversible within: 21 days
Remarks on result:
other: score 1 in 2 rabbits at day 21
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48, and 72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Remarks on result:
other: score 1 in 3 rabbits at day 21
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24 h
Score:
2.16
Max. score:
4
Reversibility:
fully reversible within: 13 days
Irritant / corrosive response data:
The individual results are presented in the Tables below. Critical for evaluation is the opacity of the cornea (grading score 2, area involved score 2) accompanied by circumcorneal injection and iritis at termination (day 21) in 2 out of 6 rabbits (grade 1 for erythema and edema was also found in these 2 animals at termination) and necrosis of nictitating and mucous membrane of the conjunctivae in all rabbits reported the first 72 h.
The authors calculated an irritation index of 31.96 (max. value 110; related to the first 4 time points).
Other effects:
no

Any other information on results incl. tables

Opacity of the cornea
Scoring according to OECD405 (Op) or according to the Table 'Scoring of the area of cornea involved' (Ar)

Rabbit

1 h

24 h

48 h

72 h

6 d

8 d

10 d

13 d

17 d

21 d

Op

Ar

Op

Ar

Op

Ar

Op

Ar

Op

Ar

Op

Ar

Op

Ar

Op

Ar

Op

Ar

Op

Ar

M1

1

4

1

3

2

2

2

3

2

3

1

4

1

4

0

0

0

0

0

0

M2

1

2

1

4

1

4

1

3

1

2

1

2

1

2

1

2

2

2

2

2

M3

1

1

1

3

1

3

1

2

2

2

2

1

2

1

2

2

2

2

2

2

F1

1

2

1

4

1

4

2

3

2

1

1

1

0

0

0

0

0

0

0

0

F2

1

3

2

3

2

2

1

2

0

0

0

0

0

0

0

0

0

0

0

0

F3

1

2

1

4

1

3

2

3

2

1

0

0

0

0

0

0

0

0

0

0

M: male; F: female; Op: grade of corneal opacity; Ar: area of cornea involved

x

x

Effects on iris

Scoring according to OECD405

rabbit

1 h

24 h

48 h

72 h

6 d

8 d

10 d

13 d

17 d

21 d

Ir

Ad

Ir

Ad

Ir

Ad

Ir

Ad

Ir

Ad

Ir

Ad

Ir

Ad

Ir

Ad

Ir

Ad

Ir

Ad

M1

1

R

1

R

1

R

1

R

1

R, In

1

In

1

In

1

In

0

0

0

0

M2

0

0

0

0

0

0

0

0

1

In

1

In

1

In

1

In

1

In

1

In

M3

0

0

1

R

0

0

1

R

0

0

1

In

1

In

1

In

1

In

1

In

F1

0

0

1

R

0

0

1

R

0

0

0

0

0

0

0

0

0

0

0

0

F2

0

0

0

0

0

0

1

R

0

0

0

0

0

0

0

0

0

0

0

0

F3

0

0

0

0

0

0

1

R

0

0

0

0

0

0

0

0

0

0

0

0

M: male; F: female; Ir:  Scoring of iris according to OECD405; Ad: additional effects described; In: circumcorneal injection; R: iris redened

x

x

x

Erythema (E) and chemosis (C) of the conjunctivae scored according to OECD405

Discharge (D) from conjunctivae (scoring system see Table above in methods)

Rab- bit

1 h

24 h

48 h

72 h

6 d

8 d

10 d

13 d

17 d

21 d

E/C

D/Ad

E/C

D/Ad

E/C

D/Ad

E/C

D/Ad

E/C

D/Ad

E/C

D/Ad

E/C

D/Ad

E/C

D/Ad

E/C

D/Ad

E/C

D/Ad

M1

3/1

3/-

3/2

2/N

3/1

1/N

3/1

1/N

3/1

1/N

3/0

0/-

2/0

0/-

1/0

0/-

1/0

0/-

0/0

0/-

M2

2/2

3/-

3/3

2/N

3/2

2/NA

3/1

1/N

3/1

2/N

3/1

2/N

3/1

1/-

1/0

0/-

1/0

0/-

1/0

0/-

M3

2/2

3/-

3/2

2/N

3/1

1/N

3/1

2/N

2/0

2/-

2/0

1/-

1/0

0/-

2/0

0/-

1/0

0/-

1/0

0/-

F1

2/2

3/-

3/2

1/N

3/1

0/NA

3/1

1/NA

1/0

0/-

1/0

0/-

1/0

0/-

1/0

0/-

1/0

0/-

1/0

0/-

F2

2/2

3/-

3/2

1/N

3/1

2/NA

3/1

1/N

1/0

0/-

1/0

0/-

0/0

0/-

0/0

0/-

0/0

0/-

0/0

0/-

F3

3/2

3/-

3/2

1/N

3/1

1/NA

3/1

1/N

1/0

0/-

1/0

0/-

0/0

0/-

0/0

0/-

0/0

0/-

0/0

0/-

M: male; F: female; Ad: additional effects documented; N: partly necrosis of nictitating and mucous membrane; A: ablation of the mucous membrane

Applicant's summary and conclusion

Conclusions:
The instillation of the test substance resulted in serious damage to the eyes.
Executive summary:

This study is conducted according to OECD Guideline 405 (adopted 1981).

Three Males and 3 females rabbits received instillations of ca. 100 mg crystalline test substance into the left conjunctival sac, the right eye was untreated (control). Scoring according to the Guideline was performed 1, 24, 48, and 72 hours and 6, 8, 10, 13, 17, and 21 days after instillation. The first 72 h after instillation necrosis of nictitating and mucous membrane of the conjunctivae of all 6 rabbits were reported. At termination (day 21) irreversible damage in 2 out of 6 rabbits was obvious: opacity of the cornea (grading score 2, area involved score 2) accompanied by circumcorneal injection and iritis.

Conclusion: The instillation of the test substance resulted in serious damage to the eyes.