Registration Dossier

Administrative data

Description of key information

No sensitisation potential was reported in guinea pigs upon dermal sensitisation and challenge with 22.9% TIPA in a study similar to EPA guidelines. In a Schwartz-Peck Prophetic Patch test with human volunteers, a lotion containing 1.1% TIPA was found not an irritant, sensitiser, or phototoxin.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Remarks:
in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
EPA OPP 81-6 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
other: Modification of the Maguire method (H.C. Maguire, 1973. The Bioassay of Contact Allergens in the Guinea Pig. J. Soc. Cosmet. Chem., 24, 151-162.)
Justification for non-LLNA method:
Currently no LLNA study is available for assessment. The Modified Maguire method has been carried out as an animal test to predict human sensitization and is recommended by international test guidelines such as EPA.
Specific details on test material used for the study:
22.9% triisopropanolamine in water
Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
The skin sensitization test was conducted on male Hartley albino guinea pigs weighing between 260 and 325 g (Charles River Breeding Laboratories, Inc., Kingston, NY). Upon arrival at the laboratory the guinea pigs were examined for health status by the laboratory veterinarian. Animals were housed five per wire-bottom cage in rooms designed to control temperature at approximately 22C, relative humidity at approximately 50% and a twelve-hour photocycle. Animal care facilities are fully accredited by the American Association for Accreditation of Laboratory Animal Care. They were supplied with Purina Certified Guinea Pig Chow #5026 (Ralston Purina Company, St. Louis, Missouri) and tap water ad libitum. Analysis of the certified feed was performed by the Ralston Purina Company to confirm that the diet provided adequate nutrition and to quantitate low levels of selected chemical contaminants. Analysis of the tap water (municipal water supply) was routinely performed according to the Standard Operating Procedures of the Mammalian and Environmental Toxicology Research Laboratory. All animals were acclimated to the laboratory environment at least one week prior to initiation of the study. Each animal was identified by a numbered metal ear tag and was randomly assigned to treatment groups.
Route:
epicutaneous, semiocclusive
Vehicle:
water
Concentration / amount:
22.9% / 0.1 mL
Day(s)/duration:
4 applications within 10-day period
No.:
#1
Route:
epicutaneous, open
Vehicle:
water
Concentration / amount:
22.9% / 0.1 mL
Day(s)/duration:
single application after 2 weeks
No. of animals per dose:
10
Details on study design:
The back of each guinea pig was clipped free of hair approximately 48 hours prior to study initiation. Twenty-four hours prior to the first application, Neet (hair cream remover) was applied over the clipped area to remove any remaining hair. Following this procedure, ten guinea pigs received four applications of the test material within ten days during the insult phase of the study. An additional group of ten guinea pigs received DER 331 epoxy resin as a 10% solution in DOWANOL DPM/Tween 80 (9:1). This epoxy resin is a known skin sensitizer and served as a positive control. Each insult application consisted of 0.1 mL of the test material or the positive control applied to an approximately 15 mm x 15 mm gauze square patch placed on the back of the guinea pig. This patch was covered with Micropore and secured with adhesive tape. At the time of the third application, a total of 0.2 mL of Freund's Adjuvant (Bacto-Adjuvant complete, H37RA DIFCO Laboratories, Detroit, Michigan) was injected intradermally at multiple points adjacent to the insult site. Observations for redness and/or edema were recorded each time the insult patches were removed. At the time of the last observation, the toe nails and distal portion of both rear feet were wrapped with adhesive tape. The animals were allowed to rest for at least two weeks. After the rest period, both flanks of the animal were clipped and the left flank was challenged with the test material or positive control. The right flanks of controls were challenged with solvent. The challenge application was not covered. Skin responses at these sites were recorded at 24 and 48 hours post-application. Guinea pigs were weighed weekly throughout the study.

Routine monitoring was limited to animal husbandry procedures required to ensure the availability of food and water. All guinea pigs were humanely euthanatized at study termination.
Challenge controls:
The right flanks of controls were challenged with solvent.
Positive control substance(s):
yes
Remarks:
DER 331 epoxy resin as a 10% solution in Dowanol DPM/Tween 80 (9:1)
Positive control results:
Slight to marked hyperemia was observed on ten of ten guinea pigs challenged with DER 331. The observed response in each animal was considered to be a positive response.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
22.9%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
22.9%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
10%
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
slight to marked hyperemia
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
10%
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
slight to marked hyperemia
Remarks on result:
positive indication of skin sensitisation
Group:
negative control
Remarks on result:
other: no information

None of the guinea pigs challenged with the test material revealed any signs of hyperemia or edema.

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

TIPA was given to 10 male Hartley albino guinea pigs at 22.9% in water for 4 epicutaneous, semiocclusive applications within a 10-day period (induction phase) (study according to EPA guidelines). After a two week rest period, animals were dermally challenged (uncovered) and the skin responses were recorded 24 and 48 hours post-application. No signs of sensitisation (i.e. hyperemia or edema) were observed after TIPA exposure. Sensitisation was verified in a positive control group (Dow, 1986).

In a human Schwartz-Peck Prophetic Patch test the irritation, sensitisation and phototoxicity of a lotion containing 1.1% TIPA was investigated in 98 volunteers (Research Testing Laboratories, 1975). Ninety-eight panelists participated in a Schwartz-Peck Prophetic Patch test to determine the irritation, sensitisation, and phototoxicity of a lotion product containing 1.1 % TIPA. Open and occlusive patches were applied for 48 h, and results were scored according to the International Contact Dermatitis Research Group procedure with a 0-3+ scoring scale. After a non-treatment period of approximately 14 days, a second set of open and occlusive patches was applied and scored 48 h later. After scoring the second occlusive patch reactions, these same test sites of all panelists were irradiated for 1 minute with a Hanovia Tanette Mark I Lamp (wavelength 5600 Angstroms). This site was scored for phototoxicity 48 h later. No reactions were observed at the first or second open patch, the first occlusive patch, or 48 h after irradiation. Four subjects had 1+ (weak, nonvesicular) reactions to the second occlusive patch, and one subject had a 2+ (strong, edematous or vesicular) reaction to the second occlusive patch. These reactions were not considered clinically significant. The product was not an irritant, phototoxin, or sensitiser under these test conditions.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

No data are available. However, no positive human data are available suggesting that the substance causes respiratory tract sensitisation.

Justification for classification or non-classification

Based on the results of the dermal sensitisation test, TIPA does not need to be classified according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.