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Administrative data

Description of key information

In the key study, TIPA caused skin irritation (with maximum scores of 4 for erythema and edema according to OECD TG 404) that was reversible after 24 hours (Huels AG, 1985). In a Schwartz-Peck Prophetic Patch test with humans, no indications of skin irritation were observed (Research Testing Laboratories, Inc (1975)). In the key study for eye irritation, TIPA was determined to be a severe irritant, resulting in effects that were not reversible within 21 days in one animal, when delivered into the eyes of small white Russian rabbits undiluted (Huels AG, 1985).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
September 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
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted May 12, 1981
Deviations:
no
GLP compliance:
no
Specific details on test material used for the study:
- Substance type: pure active substance
- Physical state: white crystals
- Analytical purity: approx. 99 %
- Impurities (identity and concentrations): < 1 % Diisopropanolamine
Species:
rabbit
Strain:
other: Small White Russian
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Fa. Dr. Karl Thomae GmbH, Biberach, Germany
- Age at study initiation: no data
- Weight at study initiation: 2.0 - 2.6 kg
- Housing: single housing in stainless steel cages
- Diet (e.g. ad libitum): Ssniff K4 complete feed for rabbits, ad libitum, supplied by Ssniff Spezialfutter GmbH, Soest, Germany
- Water (e.g. ad libitum): Drinking water ad libitum, supplied by Gelsenwasser, Wasserwerk Haltern, Germany
- 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
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
Duration of treatment / exposure:
4 hours
Observation period:
72 hours after patch removal
Number of animals:
6 (3 male, 3 female)
Details on study design:
TEST SITE
- Area of exposure: 6 cm² of shaved skin of the dorsal and lateral parts of the trunk of the animals
- % coverage: not mentioned
- Type of wrap if used: on the application area a mull patch (2,5 x 2,5 cm) was placed, which was covered with a polyethylen film (6 x 6 cm). The application area was then immobilised with an elastic dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with warm water
- Time after start of exposure: 4 hours

SCORING SYSTEM: according to OECD guideline 404
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
8
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
see table 1

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

Score at time point / Reversibility

Erythema

Edema

Max. score: 4

Max. score: 4

60 min

0/1/0/0/1/0

0/0/0/0/0/0 

24 h

 0/0/0/0/0/0

0/0/0/0/0/0 

48 h

 0/0/0/0/0/0

 0/0/0/0/0/0

72 h

0/0/0/0/0/0 

0/0/0/0/0/0 

Average 24h, 48h, 72h

 0.0

0.0 

Reversibility*)

 c.

 n. a.

Average time (unit) for reversion

 60 min.

 n. a.

 *) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

 

Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
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
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted 12 May 1981
Deviations:
no
GLP compliance:
no
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
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
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)
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.

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
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.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Additional information

Skin Irritation

In the key study, TIPA was applied to the shaved skin on the dorsal and lateral portion of the trunk of small white Russian rabbits under semiocclusive conditions for 4 hours. Rabbits were observed for 14 days after exposure. TIPA caused minimal irritation, that was reversible after 24 hours. The mean erythema score and edema score were both 0 for the 24 -72 h time point (Huels AG, 1985). In another study, TIPA was administered to the abdomen of New Zealand white rabbits for several applications resulting in continuous contact with intact skin (either unoccluded or under cotton gauze); moderate redness, very slight swelling, slight exfoliation and a superficial burn developed (Dow, 1980).

These findings are supported by another study where skin irritation was investigated in Vienna White rabbits, which were exposed to TIPA for up to 20 hours under occlusive conditions, in a study performed according to a BASF internal method. Slight irritation was only observed (average erythema score of 1.5) after 20 hours of exposure, which was fully reversible within 6 days in all but one animal. Thus, TIPA was judged to be only slightly irritating to the skin (BASF, 1966). No erythema and edema were noted after 1, 5 and 15 minutes exposure.

In a Schwartz-Peck Prophetic Patch test with humans, no indications of skin irritation were observed (Research Testing Laboratories, Inc (1975), IUCLID section 7.10.4).

 

Eye Irritation

In the key study for eye irritation, TIPA was determined to be a severe irritant, resulting in effects that were not reversible within 21 days in one animal, when delivered into the eyes of small white Russian rabbits undiluted (Huels AG, 1985).

In a supporting study performed according to a BASF internal method, TIPA was applied to the eyes of 2 Vienna White rabbits. Eye irritation was investigated up to 8 days following exposure. Application caused slight opacity, slight to moderate erythema and chemosis and in one animal cilliar injections. Erythema, chemosis and iritis symptoms were reversible by the end of the observation period, but one animal still showed opacity. TIPA was judged as being irritating to the eyes (BASF, 1966).

 

Respiratory Irritation

In a study on respiratory irritation, mice were exposed to aerosol concentrations of 329 to 1070 mg/m3 TIPA (Detwiler-Okabayashi, 1996). The 3-hour exposure caused sensory (immediate onset) and pulmonary irritation (delayed onset). No mortality was observed. Post-exposure recovery of the breathing frequency was moderate to good. The RD50 (concentration capable of evoking a 50% decrease in mean breathing frequency; -/+ 95% CI) was calculated to be 815 (570 - 1069) mg/m3.

Justification for classification or non-classification

Based on the available data, TIPA does not need to be classified as irritating to the skin according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

Based on the findings TIPA needs to be classified as Eye Dam. 1, H318: Causes serious eye damage in accordance with EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008