Tripropylamine

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

Hackett-Fields 1 JULI 1988 to 10 AUG 1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study (EPA OTS 798.4100)

Qualifier:

according to guideline

Guideline:

EPA OTS 798.4100 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes

Type of study:

Buehler test

Justification for non-LLNA method:

Bühler test with Guinea pigs was performed before the LLNA was set as preferred test method.

Species:

guinea pig

Strain:

Hartley

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Davidson's Mills Farm, South Brunswick, NJ
- Weight at study initiation: 332-449 g
- Housing: gang-caged
- Diet (ad libitum): Purina guinea pig pellets
- Water (ad libitum): tap water
- Acclimation period: 24 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.8-22.2

Route:

epicutaneous, semiocclusive

Vehicle:

other: 95% ethanol

Concentration / amount:

pre-test : 1, 2, 4, 6.25, 8, 25, 50%
induction: 4% (highest non irritating dose)
challenge: 4%

Route:

epicutaneous, semiocclusive

Vehicle:

other: 95% ethanol

Concentration / amount:

pre-test : 1, 2, 4, 6.25, 8, 25, 50%
induction: 4% (highest non irritating dose)
challenge: 4%

No. of animals per dose:

15 (5 of them were naive controls)

Details on study design:

RANGE FINDING TESTS:
The maximum non-irritating concentration of 4 % was determined in a range-finding test (4 animals in two sets, application of the test substance to the clipped dorsal thoracolumbar region, 4 test sites per animal, 0.5 ml of 1, 2, 4, 6.25, 8, 25 and 50% dilutions of the test substance in 95% ethanol, 6 h of semiocclusive exposure and examination 24 h after initial application)

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 10
- Exposure period: 6 h each
- Test groups: 10 animals
- Control group: 5 naive control animals per group
- Site: clipped dorsal thoracolumbar region
- Duration: 3.5 weeks
- Concentrations: 4%


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 14 days after 10th induction application
- Exposure period: 6 h (not stated in study report, but according to guideline)
- Test groups: 10 animals
- Control group: 5 naive control animals per group
- Site: untreated site on left flank
- Concentrations: 4%
- Evaluation (hr after challenge): 24 and 48 h after challenge

Challenge controls:

5 naive controls per group

Positive control substance(s):

yes

Remarks:

0.08% dinitrochlorobenzene (DNCB) in 95% ethanol

Positive control results:

6/10 test sites were erythematous 24 h after challenge, 4/10 were clear. At the 48 h reading there were 8 sites with erythema and 2 without effect. Scores ranged from 0.5 (very faint, nonconfluent) to 3 (strong).

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

4%

No. with + reactions:

2

Total no. in group:

10

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 4%. No with. + reactions: 2.0. Total no. in groups: 10.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

4%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 4%. No with. + reactions: 0.0. Total no. in groups: 10.0.

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

No. with + reactions:

0

Total no. in group:

5

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 5.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

No. with + reactions:

0

Total no. in group:

5

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 5.0.

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

0.08% DNCB

No. with + reactions:

6

Total no. in group:

10

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 0.08% DNCB. No with. + reactions: 6.0. Total no. in groups: 10.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

positive control

Dose level:

0.08% DNCB

No. with + reactions:

8

Total no. in group:

10

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 0.08% DNCB. No with. + reactions: 8.0. Total no. in groups: 10.0.

All animals appeared active and healthy and gained weight during the induction phase and in the period to challenge. Induction phase: The occurence of generall sporadic and transient very faint non-confluent erythema (score 0.5) was observed during the first two weeks of the induction phase. One animal had eschar at the test site between the 5th and 6th induction treatment which did not re-occur after change of the test site. One animal showed a faint erythema after the 9th induction. Challenge: Two sites challenged with the test substance showed very faint, non-confluent erythema 24 h after challenge (score 0.5; remaining animals: score 0). No reaction (score 0) was observed in all animals 48 h after application.

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study the test substance was not sensitising in a Buehler guinea pig sensitisation test.

Executive summary:

In this study according to EPA guideline 798.4100 a highest non-irritating concentration of a 4% dilution of the test substance (89% purity) in 95% ethanol was determined in a pre-test. 10 young adult male guinea pigs were treated ten times for 6 h each with this concentration during a 3.5 week induction phase. Another group of 10 males were treated equally with the positive control substance (0.08% dinitrochlorobenzene in 95% ethanol). The occurrence of general sporadic and transient very faint non-confluent erythema was observed during the first two weeks of the induction phase. One animal developed transient eschar at the test site which did not re-occur after change of the test site. One animal showed a faint erythema after the 9th induction. Challenge: Fourteen days after the last induction a challenge with the same concentration of test substance or the positive control substance was performed at a naive site of each animal and the reaction was scored 24 and 48 h later. 5 animals per each group served as naive controls and were treated with the test material or control material only at challenge. Two animals challenged with the test substance showed very faint, non-confluent erythema 24 h after challenge (Score 0.5, remaining animals: score: 0). No reaction was observed in all animals 48 h after application. Based on these results the test substance was judged to be not sensitising. The positive control substance produced a positive response (Pennwalt/PSL, 1988). This study was judged to be reliable (RL1) and selected as key study.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

To assess skin sensitisation potential of tripropylamine the following sensitisation studies on the related substances were used:

EPA Guinea Pig Skin Sensitisation Test (Buehler) (tributylamine, CAS No. 102 -82 -9)

In this study according to EPA guideline 798.4100 a highest non-irritating concentration of a 4% dilution of the test substance (89% purity) in 95% ethanol was determined in a pre-test (Hackett-Fields, 1988, Report No. T-7718). 10 young adult male guinea pigs were treated ten times for 6 h each with this concentration during a 3.5 week induction phase. Another group of 10 males were treated equally with the positive control substance (0.08% dinitrochlorobenzene in 95% ethanol). The occurrence of general sporadic and transient very faint non-confluent erythema was observed during the first two weeks of the induction phase. One animal developed transient eschar at the test site which did not re-occur after change of the test site. One animal showed a faint erythema after the 9th induction. Challenge: Fourteen days after the last induction a challenge with the same concentration of test substance or the positive control substance was performed at a naive site of each animal and the reaction was scored 24 and 48 h later. 5 animals per each group served as naive controls and were treated with the test material or control material only at challenge. Two animals challenged with the test substance showed very faint, non-confluent erythema 24 h after challenge (Score 0.5, remaining animals: score: 0). No reaction was observed in all animals 48 h after application. Based on these results the test substance was judged to be not sensitising. The positive control substance produced a positive response.

Sensitisation Intracutaneous Method (triethylamine, CAS No. 121 -44 -8)

Triethylamine was tested in male albino guinea pigs for its sensitisation potential in an Intracutaneous Test (Carpenter, 1958, Report No. 86 -870001424). 0.1% solutions of test material in 0.75% saline was administered to 20 test animals by intracutaneous injection 8 times (not specified if once each day). Challenge doses were given 3 weeks after the last sensitising dose. 8 animals were infected, killed or died on study. No positive sensitisation responses were noted in the 12 survived animals. The animals on study were considered to be not entirely healthy. Therefore if the test substance was a sensitiser, such animals would be more refractory to sensitisation. The test substance was considered to be not sensitising by the author of the study report.

Mouse Ear Swelling Test (Sensitisation Assay) (triethylamine, CAS No. 121 -44 -8)

The study was conducted in order to evaluate the allergic contact sensitisation potential of triethylamine in mice (Blaszcak, 1987; Report No. 6717 -86). The test design was based on procedures described in "Development and Validation of an Alternative Dermal Sensitisation Test: Mouse Ear Swelling Test (MEST)" (Shayne et al., 1986). The concentrations of test material and positive control substance at induction and challenge phases were determined in a range-finding study. For the main study, on day 0, 0.02 mL of a 50% concentration of FCA in water was administered by intradermal injection to two clipped sites of abdomen of two groups of albino mice (CF1 BR) (10/group). Thereafter the animals were treated topically with 100 µL either 1.0 % test material in vehicle or 0.5% (w/v) 2,4 -dinitrochlorobenzene (DNCB)(positive control substance) in vehicle. 70% ethanol served as vehicle. Another 15 animals (5/group) were taken on study to serve as irritation control group in order to differentiate reactions produced by irritation from those produced by sensitisation. During induction phase these animals were treated with vehicle and FCA only. On days 1, 2 and 3 the same amount of the appropriate material or vehicle was administered to the test site of each animal, once each day. On the day 10, the animals were challenged topically with 10 µL of either pure test material or 1% (w/v) DNCB to the dorsal and ventral surfaces of the ear. Irritation control animals (previously treated with vehicle and FCA) were subjected to the same procedure as the test animals. The animals were also re-challenged on day 17 and the procedures were followed the same as at challenge.

Except for one animal which did not recover from the anesthesia at the 24 -hour Challenge Response Measurement (DNCB irritation control animal), all animals survived throughout the study. 80% of the animals treated with DNCB exhibited a positive sensitisation response (test ear at least 20%thicker than control ear), at 24 -hours and 100% exhibited a positive response at 48 hours. There were no positive responders in the irritation control group. This positive response to a known sensitiser demonstrated the susceptibility of this group of animals to sensitisation. Animals challenged with test material exhibited no positive response at challenge or re-challenge in either the test group or irritation control groups. Thus, the test material exhibited no potential to produce sensitisation in mice.

Migrated from Short description of key information:
The nearest structural analogue TBA was not sensitising in Guinea pigs (Buehler Test) and another structural analogue TEA was not sensitising in an Intracutaneous Test and in Mouse Ear Swelling test. Therefore, TnPA is considered to be non-sensitiser.

Justification for selection of skin sensitisation endpoint:
Reliable guideline study

Justification for classification or non-classification

The structural analogue substances TEA and TBA was not sensitising in the available tests. Therefore, no sensitisation potential of TnPA is expected. TnPA does not need to be classified or labelled as skin sensitiser in accordance with CLP Regulation (EC) No 1272/2008.