Tripropylamine

Endpoint summary

Description of key information

Tri-n-propylamine is acutely toxic via oral and dermal exposure routes. Oral LD50 of 200 -2000 mg/kg bw and dermal LD50 of 430 mg/kg bw point to Cat 3 for oral and dermal routes, respectively. 1-Hour LC50 of 4.5 mg/L (corresponds to 4-hour LC50 of 1.13 mg/L) points to Cat 4 for inhalation route.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented report which meets basic scientific principles.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

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 to treatment and thereafter, on 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:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: DR. K . THOMAE GMBH, Biberach, Germany
- Age at study initiation: Young adult animals
- Weight at study initiation: male: 180 g (mean), female: 183 g (mean)
- Fasting period before study: 16 h
- Housing: 5 per cage
- Diet: Kliba Labordiaet 343, ad libitum
- Water: Tap water, ad libitum
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24 °C
- Humidity (%): 30-70 %
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 4 and 40 %
- Justification for choice of vehicle: Test substance in insoluble in aqua dest.

MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg bw

Doses:

200 and 2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: at least once per day
- Frequency of weighing: days 0, 7 and 13
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Sex:

male/female

Dose descriptor:

LD50

Effect level:

200 - 2 000 mg/kg bw

Mortality:

200 mg/kg bw: no mortality occurred.
2000 mg/kg bw: 4 males and 5 females died within 1 h after application. A further male died within 24h after application.

Clinical signs:

other: other: 200 mg/kg bw: no clinical signs 2000 mg/kg bw: Abdominal position, apathy, clonic convulsions, piloerection, salivation, staggering, tremor, twitching, poor general state.

Gross pathology:

Animals that died: General congestion.
Sacrificed animals: No pathologic findings noted.

Mortality:

Dose (mg/kg bw)	Gender	1 h	day 1	day 7	day 13
200	male	0/5	0/5	0/5	0/5
200	female	0/5	0/5	0/5	0/5
2000	male	4/5	5/5	5/5	5/5
2000	female	5/5	5/5	5/5	5/5

Weight (g):

Dose (mg/kg bw)	Gender	day 0	day 7	day 13
200	male	188	261	305
200	female	187	220	231
2000	male	171	-	-
2000	female	179	-	-

Interpretation of results:

Toxicity Category III

Remarks:

Migrated information according to the criteria in CLP, Annex I Criteria used for interpretation of results: EU

Conclusions:

An oral LD50 of 200-2000 was established for tripropylamine in rats. According to Regulation (EC) No 1272/2008, tripropylamine should be classified in Cat. 3 as an acute toxic substance by the oral route (H301 Toxic if swallowed).

Executive summary:

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. Two dose levels were used: 200 mg/kg bw and 2000 mg/kg bw. The animals were observed for mortality and for clinical symptoms of toxicity. They were weighed prior to treatment and thereafter, on 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. No mortality occurred in animals treated with 200 mg/kg bw, while 4 males and 5 females died within 1 hour after application of 2000 mg/kg bw. No clinical signs were observed in animals in the low dose group (200 mg/kg bw); the animals gained weight. In the highest dose group (2000 mg/kg bw), abdominal position, apathy, clonic convulsions, piloerection, salivation, staggering, tremor, twitching and poor general state were observed. No pathological findings were noted at necropsy in sacrificed animals. In animals that died, general congestion was noted. LD50 is in the range of 200 -2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

200 mg/kg bw

Quality of whole database:

good quality

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1975-06-18 to 1975-08-21

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: no GLP, brief, little information on test method (e.g. no information on acclimatisation, weight of animals, lighting)

Qualifier:

no guideline followed

Principles of method if other than guideline:

Ten male, albino rats were placed in a 70- litre, all glass exposure chamber and exposed to a saturated atmosphere of the test material in air for one hour. The material was administered as an aerosol with particles 3-5 microns in diameter. The rats were subjected to average concentrations of 4.5 mg/L, 7.4 mg/L or 12.8mg/L during the exposure period.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: albino

Sex:

male

Details on test animals or test system and environmental conditions:

no data available

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

other: desiccated air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: all glass exposure chamber
- Exposure chamber volume: 70 litres
- Method of holding animals in test chamber: free
- Source and rate of air: air was passed through a desicant prior to being passed through the test material, the rate of flow was 36 litres per minute (4.5 mg/L) or 43 litres per minute (7.4mg/L) and 25.9 litres per minute (12.8 mg/L)
- Method of conditioning air: air was passed through a desicant prior to being passed through the test material.
- System of generating particulates/aerosols: the material was administered as an aerosol with particles 3~5 microns in diameter.
- Temperature, humidity, pressure in air chamber: 72°F

TEST ATMOSPHERE
- Brief description of analytical method used: The air was passed through a deslcant prior to being passed through the test material. By differential weighing it was calculated that the rats were subjected to a concentration of 4.5 mg/L, 7.4 mg/L or 12.8 mg/L during the exposure period. These are averages values over the one hour period.
- Samples taken from breathing zone: no data

TEST ATMOSPHERE (if not tabulated)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): particles 3-5 microns in diameter

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

1 h

Concentrations:

4.5 mg/L, 7.4 mg/L, 12.8 mg/L

No. of animals per sex per dose:

10 male

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: not given
- Necropsy of survivors performed: no data
- Other examinations performed: clinical signs

Sex:

male

Dose descriptor:

LC50

Effect level:

ca. 4.5 other: mg/L

Exp. duration:

1 h

Mortality:

4.5 mg/L: 6 rats died
7.4 mg/L: all rats died within 40 min
12.8 mg/L: all rats died within 35 min

Clinical signs:

other: 4.5 mg/L: within 30 min all rats exhibited body tremors, by 40 min the rats were inactive; the tremors ceased within 24 hours 7.4 mg/L: within 20 min all the rats exhibited vigorous pawing and then tremors, by 30 min all rats exhibited tremors 12.8 mg/L:

Body weight:

no data

Gross pathology:

no data

Other findings:

no other findings reported

Dose of 4.5 mg/L:

Within 30 minutes all rats exhibited body tremors. By 40 minutes the rats were inactive. Within 60 minutes 2 rats were dead and the remaining rats were still exhibited tremors. Within 15 minutes after exposure 4 additional rats died. Tremors ceased within 24 hours and there were no additional deaths during the 14 day observation period. A total of 6 rats died during the 14 day observation period.

Dose of 7.4 mg/L:

Within 20 minutes the rats exhibited vigorous pawing and then tremors. By 30 minutes all rats exhibited tremors. By 40 minutes all 10 rats were dead.

Dose of 12.8 mg/L:

Initially the rats were more active than normal but soon they exhibited decreased activity. Within 10 minutes they exhibited whole body tremors and after 20 minutes the rats were still twitching. By 35 minutes all 10 rats were dead.

Interpretation of results:

Toxicity Category III

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The study was performed without following a specific Guideline and still considered to be of the high quality (reliability Klimisch 2). The test material did induce signs of acute inhalation toxicity in rats under the conditions of the test. LC50 of 4.5 mg/L generated using 1 hour exposure corresponds to a 4-hour LC50 of 2.25 mg/L (obtained by dividing by a factor of 2). LC50 of 2.25 mg/L points to Cat. 3 (H331 Toxic if inhaled).

Executive summary:

A study on the acute inhalation toxicity of tri-n-propylamine (aerosol) for rats was conducted. The exposure was conducted via whole-body exposure of groups of 10 male albino rats to an aerosol (doses: 4.5 mg/L, 7.4. mg/L and 12.8 mg/L) for a single 1-hour period. The particles were 3-5 microns in diameter. After exposure the animals were observed for 14 days. At 12.8 mg/L the rats exhibited initially an increased activity than normal but soon they exhibited decreased activity. Within 10 minutes they exhibited whole body tremors and after 20 minutes the rats were still twitching. By 35 minutes all 10 rats were dead. At 7.4 mg/L the rats exhibited within 20 minutes vigorous pawing and then tremors. By 30 minutes all rats exhibited tremors. By 40 minutes all 10 rats were dead. At 4.5 mg/L all rats exhibited body tremors within 30 minutes. By 40 minutes the rats were inactive. Within 60 minutes 2 rats were dead and the remaining rats were still exhibited tremors. Within 15 minutes after exposure 4 additional rats died. Tremors ceased within 24 hours and there were no additional deaths during the 14 day observation period. A total of 6 rats died during the 14 day observation period. No information is given on body weight changes or pathological examinations.The study thus shows that the test substance has a high acute inhalation toxicity. In conclusion, tri-n-propylamine was found to have a LC50 (median lethal dose) of approximately 4.5 mg./L for albino rats and thus would be considered toxic (acute tox. cat. 3).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

1 125 mg/m³ air

Quality of whole database:

good quality

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable well documented publication which meets basic scientific principles

Qualifier:

no guideline followed

Principles of method if other than guideline:

Penetration of rabbit skin is estimated by a technique closely akin to the one-day cuff method of Draize and associate. No information is on test animals and their environmental conditions as well as health state after the treatment.

GLP compliance:

no

Remarks:

the study was conducted prior adoption of GLP

Test type:

other: penetration on rabbit skin

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2.0-3.5 kg

Type of coverage:

occlusive

Vehicle:

not specified

Details on dermal exposure:

TEST SITE
- Area of exposure: back
- % coverage: entire trunk
- Type of wrap if used: imperious plastic film
The animals were immobilized during the exposure.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): no data; Dosages greater than 20 mL/kg could not be retained in contact with the skin.

Duration of exposure:

24 hours

Doses:

No data

No. of animals per sex per dose:

4

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: no data
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: no data

Statistics:

Based upon mortalities during a 14-day observation period, the most probable LD50 value and its fiducial range are estimated by the method of Thompson using the Tables of Weil. The figures' in parentheses show limits of ± 1.96 standard deviations while the absence of parentheses indicates that no range is calculable because no dosage resulted in fractional mortality.

Sex:

male

Dose descriptor:

LD50

Effect level:

430 mg/kg bw

Based on:

test mat.

Remarks:

0.57 mL/kg bw

Remarks on result:

other: (0.26-1.23), the dose is calculated based on density of 0.7557 g/cm³

Mortality:

No data

Clinical signs:

other: other: No data

Gross pathology:

No data

Interpretation of results:

Toxicity Category III

Remarks:

Migrated information GHS Criteria used for interpretation of results: EU

Conclusions:

LD50 of 0.57 mL/kg bw (corresponding to 430 mg/kg bw) was reported for tripropylamine. According to Regulation (EC) No 1272/2008, tripropylamine should be classified in Cat 3 as acute toxic substance by dermal route (H301 Toxic in contact with skin).

Executive summary:

Tripropylamine was tested in a range-finding toxicity study in New Zealand rabbits (Smyth et al., 1969). Penetration of rabbit skin is estimated by a technique closely akin to the one-day cuff method of Draize and associates using groups of four male albino New Zealand rabbits weighing 2.5 to 3.5 kg. The fur is removed from the entire trunk by clipping, and the dose is retained beneath an impervious plastic film. Dosages greater than 20 ml/kg cannot be retained in contact with the skin. The animals are immobilized during the 24-hour contact period, after which the film is removed and the rabbits are caged for the subsequent 14-day observation period. Based upon mortalities during 14 -day observation period, the most probable LD50 value and its fiducial range are estimated by the method of Thompson using the Tables of Weil (references are cited in the publication). LD50 of 0.57 mL/kg bw (range 0.26 - 1.23) was reported for tripropylamine. The range shows limit of± 1.96 standard deviation. Based on the density of 0.7557 g/cm³ (Lechte, 2010), 0.57 mL/kg bw corresponds to 430 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

430 mg/kg bw

Quality of whole database:

good quality

Additional information

Acute toxicity: oral

In a key study, conducted according to an internal BASF method which in principle is comparable to the OECD Guideline 401 (BASF, 1990; Report No. 10A0756/891202), a test group consisting of 5 animals/sex was treated by a single gavage application with an aqueous solution of the test substance. Two dose levels were used: 200 mg/kg bw and 2000 mg/kg bw. The animals were observed for mortality and for clinical symptoms of toxicity. They were weighed prior to treatment and thereafter, on 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. No mortality occurred in animals treated with 200 mg/kg bw while 4 males and 5 females died within 1 hour after application of 2000 mg/kg bw. No clinical signs were observed in animals in the low dose group (200 mg/kg bw); the animals gained weight. In the highest dose group (2000 mg/kg bw), abdominal position, apathy, clonic convulsions, piloerection, salivation, staggering, tremor, twitching and poor general state were observed. No pathological findings were noted at necropsy in sacrificed animals. In animals that died, general congestion was noted. LD50 is in the range of 200 -2000 mg/kg bw.

In a supporting study, conducted according to an internal BASF method and which in principle is comparable to the OECD Guideline 401 (BASF, 1977; Report No. XXVI/207), a test group consisting of 5 animals/sex was treated by a single gavage application with an aqueous solution of the test substance. The doses tested were 161, 237, 348 and 510 mg/kg bw. The animals were observed for mortality and for clinical symptoms of toxicity. They were weighed prior to treatment and thereafter, on 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. No animals died in the lowest dose group (161 mg/kg bw). The mortality in the other dose groups was dose-dependent. The following clinical signs were observed: dyspnoea, apathy, abdominal-lateral position, partly staggering, tremor, tonic-clonic convulsions, exsiccosis, partly exophthalmia, salivation and poor general state. Normal body weight gain was observed in the survived animals. In animals that died, an acute dilatation of heart and acute congestive hyperaemia were noted. No abnormalities were detected in the sacrificed animals.

In a publication, tripropylamine was tested in a range-finding toxicity study in Carworth-Wistar rats (Smyth et al., 1969). A single dose of the test substance was administered to groups of five non-fasted male rats by gastric intubation. The dosages were arranged in a logarithmic series differing by a factor of 2. Based upon mortalities during 14 -day observation period, the most probable LD50 value and its fiducial range are estimated by the method of Thompson using the Tables of Weil (references are cited in the publication). LD50 of 0.096 mL/kg bw (range 0.071 - 0.13) was reported for tripropylamine. The range shows limit of ± 1.96 standard deviation. Based on the density of 0.7557 g/cm³ (Lechte, 2010), 0.096 mL/kg bw corresponds to 72.5 mg/kg bw.

Acute toxicity: inhalation

In a key study, the acute inhalation toxicity of tri-n-propylamine (aerosol) in rats was studied (Biosearch, 1975). The exposure was conducted via whole-body exposure of groups of 10 male albino rats to an aerosol (doses: 4.5 mg/L, 7.4. mg/L and 12.8 mg/L) for a single 1-hour period. The particles were 3-5 microns in diameter. After exposure the animals were observed for 14 days. At 12.8 mg/L the rats exhibited initially an increased activity than normal but soon they exhibited decreased activity. Within 10 minutes they exhibited whole body tremors and after 20 minutes the rats were still twitching. By 35 minutes all 10 rats were dead. At 7.4 mg/L the rats exhibited within 20 minutes vigorous pawing and then tremors. By 30 minutes all rats exhibited tremors. By 40 minutes all 10 rats were dead. At 4.5 mg/L all rats exhibited body tremors within 30 minutes. By 40 minutes the rats were inactive. Within 60 minutes 2 rats were dead and the remaining rats were still exhibited tremors. Within 15 minutes after exposure 4 additional rats died. Tremors ceased within 24 hours and there were no additional deaths during the 14 day observation period. A total of 6 rats died during the 14 day observation period. No information is given on body weight changes or pathological examinations.The study thus shows that the test substance has moderate acute inhalation toxicity. In conclusion, tri-n-propylamine was found to have a LC50 (median lethal dose) of approximately 1.13 mg/L (obtained by conversion of 1-hour LC50 value of 4.5 mg/L into 4 -hour value by dividing by a factor of 4 (for dusts and mists)) for albino rats and thus would be considered harmful (acute tox. cat. 4).

In a following-up acute inhalation study, groups of 10 male albino rats were exposed for a single 1 -hour period to an aerosol of tri-n-propylamine via whole-body exposure at concentrations of 1.99 mg/L, 2.02 mg/L and 2.10 mg/L (Biosearch, 1976). The particles were 3-5 microns in diameter. After exposure the animals were observed for 14 days. At all exposure concentrations, the rats exhibited huddling during exposure period. There were no deaths at any time during the 14 day observation period. No information is given on body weight changes or pathological examinations. The LC50 is greater than 2.1 mg/L was reported.The study provides additional information to the LC50 value of 4.5 mg/L obtained in the previous inhalation study in rats in which test material produced deaths and toxic systemic effects at concentrations of 4.5, 7.4, and 12.8 mg/L.

In a supporting study, the toxicity of tripropylamine at a saturated atmosphere at the room temperature was studied (BASF, 1977; Report No. XXVI/207). 3 rats per sex were exposed sequentially to the vapours, generated by bubbling 200 L/h air through a substance column of about 5 cm above a fritted glass disc in a glass cylinder for 3, 10 and 30 min at concentrations of 18.0, 18.3 and 18.4 mg/L, respectively. The documentation of clinical signs was performed over a period of 7 days. No animal died during 3 min exposure. 4/6 animals died within 1 hour after exposure during 10 min to the test substance. After 30 -min exposure, all animals died with the exposure time. The following clinical signs were observed in animals after 3 -min exposure: eyelids closed, intense tremor and malfunction of motion coordination. After 10 -min and 30 -min exposure: eyelids closed, intense tremor, convulsions and colourless nasal secretion. Animals that survived showed no clinical signs anymore after one hour and after one day exposure following 3-min or 10-min exposure, respectively. The surviving animals gained weight. For those animals that survived and were sacrificed after 7 days, no abnormalities were detected. Animals that died showed in the lungs infrequent pneumonic areas. The inhalation of a highly saturated vapour-air mixture represents a severe hazard (mortality within 10 minutes). An LC100 of 18 mg/L is determined for rats within 30 min.

In another supporting study, albino male Carworth-Wistar rats were exposed to vapour of tripropylamine at nominal concentration of 250 ppm (corresponds to 1462 mg/m³). The rats were observed during 14 days. 3 out of 6 rats died after exposure to the chemical (Smyth et al., 1969).

Data on read-across substances

TEA

In the GLP and OECD compliant acute 1 -hour inhalation study (International Research and Development Corporation, 1995), the exposure of rats to triethylamine caused a clear dose-dependent response.Severe toxicity leading to death was observed among rats exposed to triethylamine via inhalation.Four measured exposure concentrations were used: 2,450, 3,200, 4,000, and 5,050 ppm. Rats showed laboured breathing and tremors at all exposure levels; some also showed increased salivation and (at 3,200 ppm) excessive lacrimation. After 2,450 ppm all rats (5 male and 5 female) returned to normal by post-exposure day 5. At 3,200 ppm two female rats died immediately post-exposure, but the other 3 females and all 5 males returned to normal by post-exposure day 6. At 4,000 pm 9/10 rats died immediately after exposure, and at 5,050 ppm all 10 died immediately.

Mean body weight gains were normal after 2,450 ppm (for both male and female rats) and for female rats after 3,200 ppm. Male body weight gains were depressed during the first week after 3,200 ppm exposure, but all returned to normal by day 14. At necropsy, no macroscopic abnormalities were recorded for either the lowest or the highest exposure groups. At 3,200 ppm one male rat had bilateral corneal opacity. Four males and four females had discoloured lungs after 4,000 ppm. 1 -hour LC50 was determined to be 3496 ppm (14270 mg/m³). For the purpose of classification and labelling this value can be extrapolated to 4 -hour exposure value by dividing by a factor of 2 and then can serve as key value (Guidance on the Application of Regulation (EC) No. 1272/2008).

In a supporting study (BASF, 1960) rats were inhaled to the vapour TEA-air-mixtureduring 8 minutes. All animals died within 4 minutes. Dyspnoea was observed as clinical symptom. There were no abnormalities found by gross pathology. Meyers and Ballantyne exposed two groups of rats by inhalation during 4 hours and 2 hours, respectively (Myers and Ballantyne, 1997). Clinical observation included closed eyes, wet mouths and noses, loss of coordination, nasal irritation, salivation, wet fur, tremors, labored breathing, and convulsions. Gross necropsy revealed no remarkable pathology.

TBA

Male and female rats (5 rats/sex/dose) were subjected to test acute inhalation toxicity (Pennwalt Corp./HRC, 1987). The animals were exposed (whole body) to vapour at analytical dose levels of 0.35, 0.51, 0.73, and 2.27 mg/L test item (purity 98.5%) for 4 h and were observed for further 14 days. The animals showed abnormal breathing, restlessness, signs of irritation, closed eyelids, excessive salivation, whole body tremor and clonic convulsions, yet no symptoms were observed any more in surviving animals after 4 days. At a concentration of 0.51 mg/L air 4 out of 5 male and 2 out of 5 female rats died within 3 to 24 h. At necropsy, hypaeremic congestion of the lung was observed in deceased animals. No particular findings were observed in surviving animals. The results obtained thus led to a LC50 = 0.5 mg/L air.

Acute toxicity: dermal

Tripropylamine was tested in a range-finding toxicity study in New Zealand rabbits (Smyth et al., 1969). Penetration of rabbit skin is estimated by a technique closely akin to the one-day cuff method of Draize and associates using groups of four male albino New Zealand rabbits weighing 2.5 to 3.5 kg. The fur is removed from the entire trunk by clipping, and the dose is retained beneath an impervious plastic film. Dosages greater than 20 mL/kg cannot be retained in contact with the skin. The animals are immobilized during the 24-hour contact period, after which the film is removed and the rabbits are caged for the subsequent 14-day observation period. Based upon mortalities during 14 -day observation period, the most probable LD50 value and its fiducial range are estimated by the method of Thompson using the Tables of Weil (references are cited in the publication). LD50 of 0.57 mL/kg bw (range 0.26 - 1.23) was reported for tripropylamine. The range shows limit of± 1.96 standard deviation. Based on the density of 0.7557 g/cm³ (Lechte, 2010), 0.57 mL/kg bw corresponds to 430 mg/kg bw.

Acute toxicity: i.p. route

The study was conducted according to an internal BASF method (BASF, 1977, Report No. XXVI/207). A test group consisting of 5 animals/sex was treated by a single injection of tripropylamine into the peritoneal cavity. The dose levels were: 316, 215, 147, 121, 100, 68.1 and 46.4 µL/kg bw. The animals were observed for mortality and for clinical symptoms of toxicity. They were weighed prior to treatment and thereafter, on day 3, 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. At dose levels of 100, 68.1 and 46.4 µL/kg bw, no animal died within 14 days of observation. The mortality was dose-dependent in animals of the other dose groups. The following clinical signs were noted: dyspnoea, apathy, abdominal-lateral position, partly staggering, tremor, tonic-clonic convulsions, exsiccosis, partly exophthalmia, salivation and poor general state. Normal body weight gain was observed in the surviving animals. Neither intraabdominal precipitation of the substance nor conglutinations were observed at gross pathology. An LD50 of 75 -90 mg/kg bw (corresponds to 100 -120 µL/kg bw) was established based on the density of test material.

Justification for selection of acute toxicity – oral endpoint
A reliable study conducted according to an internal BASF method, which is similar to the principles outlined in the OECD 401 guideline.

Justification for selection of acute toxicity – inhalation endpoint
A reliable study, which allowed identification of LC50 for tripropylamine. The study report is well documented.

Justification for selection of acute toxicity – dermal endpoint
Test result originates from an old study published (1969) but conducted with the target chemical. The publication is well documented and meets basic scientific principles.

Justification for classification or non-classification

Based on the results of the acute toxicity studies, tri-n-propylamine is subject to classification and labelling for acute toxic effects according to Regulation (EC) 1272/2008:

Acute toxicity: oral: Cat 3

Acute toxicity: inhalation: Cat 4

Acute toxicity: dermal: Cat 3