Registration Dossier

Administrative data

Description of key information

Acute toxicity data indicate low toxicity: in rats the oral LD50 was 4000 mg/kg bw; in rabbits the dermal LD50 (24h) was > 5000 mg/kg bw. Inhalation exposure for 8 hours to vapour saturated with TIPA failed to cause any deaths in rats (LC50 was not determined). A 3-hour inhalation exposure to 329-1070 mg/m3 TIPA (aerosol) did not cause any mortality in mice.

Key value for chemical safety assessment

Acute toxicity: via oral route

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Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
08. Mar 1965 - 21. Mar 1965
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Principles of method if other than guideline:
BASF-Test: The study was conducted according to an internal BASF method which in principle is comparable to the OECD Guideline 401.
A test group consisting of 5 animals/sex was treated by single gavage application with an aqueous solution of the test substance. The animals were observed for mortality and for clinical symptoms of toxicity. They were weighed prior treatment and thereafter, day 3, day 7 and day 13 post-treatment. At the end of the observation period of 14 days, the surviving animals were sacrificed for the purpose of necropsy; animals that died during the observations period also were subjected to necropsy.
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
- Name of test material (as cited in study report): Triisopropanolamin
- Analytical purity: ca. 92-95 %
- Impurities (identity and concentrations): ca. 3-6 % Diisopropanolamine; <1 % Monoisopropanolamine
Species:
rat
Strain:
other: US-rats
Sex:
male/female
Details on test animals and environmental conditions:
- Weight at study initiation: male: 211 g (mean), female: 171 g (mean)
Route of administration:
oral: gavage
Vehicle:
water
Doses:
200, 1600, 3200, 4000, 5000, 6400 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 4 000 mg/kg bw
Based on:
test mat.
Mortality:
- 8 out of 10 animals died exposed to 6400 mg/kg bw
- 8 out of 10 animals died exposed to 5000 mg/kg bw
- 6 out of 10 animals died exposed to 4000 mg/kg bw
- 0 out of 10 animals died exposed to 3200, 1600, or 200 mg/kg bw
Clinical signs:
- 6400, 5000, 4000 mg/kg bw: After the application piloerrection, high stepping gait, slight stagger, mouth discharge. One hour after application beginning eye discharge, diarrhea, lateral and abdominal position, slight tremor, partly dyspnoea. On the following day heavy stagger, eye and nose crusts, hind limbs seemed to be cramped. Ruffled fur smeared at anogenital region, nose and eyes. Surviving animals were very timid and recovered from day 4.
- 3200, 1600 mg/kg bw: Symptoms similar but less distinctive as in higher doses.
- 200 mg/kg bw: On the day of application piloerrection, chewing motions, high stepping gait. On the next 2-3 days animals showed crusted noses, irregular respiration and heavy ruffled fur.
Body weight:
no data
Gross pathology:
- 6400 mg/kg bw: 1x gastro-intestinal irritation, 1x remaining substance in stomach
- 3200 mg/kg bw: 1x bronchitis and bronchiectasia
- 1600 mg/kg bw: 1x bronchitis and bronchiectasia

Mortality:

Dose (mg/kg bw)  Conc. (%)  1 h  24 h  48 h  7 days
6400  30  1/10  7/10  8/10  8/10  
5000  30  0/10  8/10  8/10  8/10  
4000  30  0/10  6/10  6/10  6/10  

3200

 30  0/10  0/10  0/10  0/10  
1600  20  0/10  0/10  0/10  0/10  
200  2  0/10  0/10  0/10  0/10  
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
4 000 mg/kg bw

Acute toxicity: via inhalation route

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Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study was conducted prior to GLP and test guidelines, but sufficient data is available for interpretation of results
Principles of method if other than guideline:
Test material was applied under an impervious cuff held in place with rubber bands and covered with a cloth bandage taped to the marginal hair. Following a 24-hour exposure period the cuffs were removed and the skin was washed with soap and water. Observations were made at this time for erythema, edema and necrosis. All animals were observed for signs of toxicity during and after exposure and were weighed at intervals up to two weeks post-application or, when practical, until any weight loss has been regained and the animals appear healthy.
GLP compliance:
no
Test type:
fixed dose procedure
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
female
Details on test animals and environmental conditions:
Male or female New Zealand albino rabbits (Langshaw Farms, Augusta, Michigan) were obtained. Twenty four hours prior to use the hair is removed from the entire trunks of New Zealand albino rabbits with electric clippers.
Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
Test material was applied under an impervious cuff held in place with rubber bands and covered with a cloth bandage taped to the marginal hair. Following a 24-hour exposure period the cuffs were removed and the skin was washed with soap and water. Observations were made at this time for erythema, edema and necrosis. All animals were observed for signs of toxicity during and after exposure and were weighed at intervals up to two weeks post-application or, when practical, until any weight loss has been regained and the animals appear healthy.
Duration of exposure:
24 hours
Doses:
5000 mg/kg
No. of animals per sex per dose:
2 females
Control animals:
no
Details on study design:
Test material was applied under an impervious cuff held in place with rubber bands and covered with a cloth bandage taped to the marginal hair. Following a 24-hour exposure period the cuffs were removed and the skin was washed with soap and water. Observations were made at this time for erythema, edema and necrosis. All animals were observed for signs of toxicity during and after exposure and were weighed at intervals up to two weeks post-application or, when practical, until any weight loss has been regained and the animals appear healthy.
Statistics:
no data
Preliminary study:
no data
Sex:
female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
no mortality was observed at 5000 mg/kg.
Clinical signs:
Twenty four hours after application of the test material, moderate erythema was noted in both rabbits, slight edema and necrosis was observed in one rabbit.
Body weight:
Both rabbits gained weight
Gross pathology:
no data
Other findings:
no additonal findings

Both rabbits survived the two-week observation period. No signs of toxicity were observed in the rabbits.

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Both rabbits survived the two-week observation period. No signs of toxicity were observed in the rabbits. The dermal LD50 is >5000 mg/kg.
Executive summary:

A sample of triisopropanolamine, also known as TIPA, was submitted for acute toxicological evaluation and definition of industrial handling hazards. Toxicity tests were conducted on this material as an 85% solution in distilled water. This is the final use dilution. Eye, skin irritation and acute percutaneous absorption tests were conducted on male or female New Zealand albino rabbits (Langshaw Farms, Augusta, Michigan).

The potential of this material to produce systemic toxicity when absorbed through the skin is low. In the acute percutaneous absorption test 2 rabbits received 5000 mg/kg of the material as an 85% aqueous solution; both rabbits survived the two-week observation period. No signs of toxicity were observed in the rabbits.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
5 000 mg/kg bw

Additional information

Acute toxicity: oral

Several non-guideline oral acute toxicity studies have been reported. In rats the oral LD50 value was determined to be 4000 mg/kg bw (BASF, 1966). At doses of 4000 mg/kg bw and higher, the following clinical signs were noted: piloerection, high stepping gait, slight stagger, mouth discharge, eye discharge, diarrhea, lateral and abdominal position, slight tremor, partly dyspnoea, heavy stagger, eye and nose crusts, cramped hind limb, ruffled fur smeared at the anogenital region, nose and mouth. Surviving animals were very timid and recovered from day 4. At necropsy, gastro-intestinal irritation and remaining substance in the stomach were observed upon macroscopic examination in one animal of the highest dose group (i.e. 6400 mg/kg bw). Other investigators established oral LD50 values in rats of 6500 mg/kg bw (Smyth et al., 1941) and 5994 mg/kg bw (Dow, 1980).

Acute toxicity: inhalation

Due to its extremely low volatility, there is a lack of data documenting the acute inhalation toxicity. As good quality data for the oral and dermal route is available, in accordance with column 2 of REACH Annex VIII, a study regarding the inhalation route is not required. One limited report stated that whole-body exposure of rats to a saturated test substance atmosphere (concentration not given) at 20°C for 8 hours failed to cause any deaths, therefore no LC50 value has been determined for this compound (BASF, 1966). In a study on respiratory irritation, mice were exposed to aerosol concentrations of 329 - 1070 mg/m3 test substance (Detwiler-Okabayashi, 1996). The 3-hour exposure caused sensory irritation (immediate onset) and pulmonary irritation (delayed onset). No mortality was observed. Post-exposure recovery of the breathing frequency was moderate to good.

Acute toxicity: dermal

Female New Zealand White rabbits were administered undiluted test material via dermal application under an impervious cuff to their trunks for 24 hours, followed by a 14-day recovery period. No evidence of systemic toxicity was reported and the LD50 was greater than 5000 mg/kg bw. Only modest skin irritation was evident following the 24 hours of exposure (Dow, 1980).

Justification for classification or non-classification

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