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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:
September to October 1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Remarks:
Study performed according to internationally accepted testing guideline, well documented

Data source

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

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted 12 May 1981
Deviations:
no
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
1,1',1''-nitrilotripropan-2-ol
EC Number:
204-528-4
EC Name:
1,1',1''-nitrilotripropan-2-ol
Cas Number:
122-20-3
Molecular formula:
C9H21NO3
IUPAC Name:
1-[bis(2-hydroxypropyl)amino]propan-2-ol
Test material form:
solid
Specific details on test material used for the study:
- Name of test material: Triisopropanolamin
- Substance type: pure active substance
- Physical state: solid, white crystals
- Analytical purity: approx. 99 %
- Impurities (identity and concentrations): < 1 % diisopropanolamine

Test animals / tissue source

Species:
rabbit
Strain:
other: Small White Russian
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Dr. Karl Thomae GmbH, Biberach, Germany
- Age at study initiation: not mentioned
- Weight at study initiation: 2.1 - 2.4 kg
- Housing: conventional, singly in stainless steel cages
- Diet (e.g. ad libitum): K4 complete feed for rabbits ad libitum, supplied by Ssniff Spezialfutter GembH, Soest, Germany
- Water (e.g. ad libitum): Drinking water ad libitum
- Acclimation period: 14 days

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

IN-LIFE DATES: From: September 4, 1985 To: October 11, 1985

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 g
Duration of treatment / exposure:
72 hours
Observation period (in vivo):
1, 24, 48 and 72 hours, and 5, 7, 10, 12, 14, 19 and 21 days after application
Number of animals or in vitro replicates:
6 (3 male, 3 female)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): with warm physiological saline
- Time after start of exposure: 72 hours

SCORING SYSTEM: according to Draize (Appraisals of the Safety of Chemicals in Foods, Drugs and Cosmetics, FDA, Austin 1, Texas, 1959)

TOOL USED TO ASSESS SCORE: sodium fluorescein solution (72 hours after administration)

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal: #1, #3, #4
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 10 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 5 days
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 10 days
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
iris score
Basis:
animal: #1, #2, #5
Time point:
24/48/72 h
Score:
0.66
Max. score:
2
Reversibility:
fully reversible within: 10 days
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 10 days
Irritation parameter:
iris score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible within: 10 days
Irritation parameter:
iris score
Basis:
animal #6
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Basis:
animal: #1, #2, #3, #4, #5
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 12 days
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
animal: #1, #3, #4, #5
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 10 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.66
Max. score:
4
Reversibility:
fully reversible within: 5 days
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Irritant / corrosive response data:
The effects were not reversible within 21 days in one animal.

Any other information on results incl. tables

Table 1: Irritant/corrosive response data for each animal at each observation time

Score at time point

Cornea

Iris

Conjunctivae

Chemosis

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

1 h

1/1/2/1/1/1

 0/0/0/0/0/1

 3/3/3/3/3/3

2/1/2/1/2/2 

24 h

1/1/1/1/2/1

 1/1/1/0/1/1

 3/3/3/3/3/3

1/1/1/1/1/1

48 h

1/2/1/1/2/1 

 0/1/1/0/1/1

 3/3/3/3/3/3

1/1/1/1/1/1 

72 h

1/1/1/1/2/1 

 1/0/1/0/0/1

3/3/3/3/3/3 

 1/0/1/1/1/1

 5 days  1/0/2/1/2/2  0/0/1/1/1/1  3/3/3/3/3/3 0/0/1/1/1/1 
 7 days  0/0/1/2/2/2 0/0/1/1/1/1   3/1/3/3/3/3  0/0/0/1/0/1
 10 days  0/0/0/0/0/3  0/0/0/0/0/1  2/1/1/1/1/3  0/0/0/0/0/1
 12 days  0/0/0/0/0/3 0/0/0/0/0/1   0/0/0/0/0/3  0/0/0/0/0/1
 14 days  0/0/0/0/0/3  0/0/0/0/0/1  0/0/0/0/0/3  0/0/0/0/0/1
 19 days  0/0/0/0/0/3  0/0/0/0/0/1  0/0/0/0/0/2  0/0/0/0/0/1
 21 days  0/0/0/0/0/3  0/0/0/0/0/1  0/0/0/0/0/2  0/0/0/0/0/1

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
TIPA was determined to be a severe irritant, resulting in effects that were not reversible within 21 days in one animal out of a group of 6.
For 5 animals, observed effects were reversible within 10 days (cornea opacity, chemosis and effects on the iris) or at least 12 days (conjunctivae score).
Executive summary:

In an acute eye irritation study according to OECD 405, six (3 female, 3 male) small white russian rabbits were treated with the undiluted test subtance. The substance was applied to the eye for an exposure of 72 hours. The untreated eye was assigned as the control. After 72 hours the eye was washed with warm physiological saline. According to the Draize score the eyes were observed and scored 1, 24, 48 and 72 hours, and 5, 7, 10, 12, 14, 19 and 21 days after application. Effects on the cornea, iris, conjunctivae and chemosis were observed in all animals. For 5 animals, the effects were reversible within 10 days (cornea opacity, chemosis and effects on the iris) or at least 12 days (conjunctivae score). The effects were not reversible in one animal after 21 days and were severe, e.g. scores up to 3 for the paramter of the cornea.

TIPA was determined to be a severe irritant, resulting in effects that were not reversible within 21 days in one animal out of a group of 6.