(hexadecylamidopropyl)trimethylammonium chloride

Endpoint summary

Description of key information

Buehler test: not sensitizing (OECD guideline 406; GLP; RL2); Induction (epicutaneous, occlusive): 100%; Challenge (epicutaneous, occlusive): 100%; sensitization in 0/10 animals

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:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

1992

Deviations:

yes

Remarks:

only 10 instead of 20 animals were used

Qualifier:

according to guideline

Guideline:

EPA OPP 81-6 (Skin Sensitisation)

GLP compliance:

yes

Type of study:

Buehler test

Justification for non-LLNA method:

A valid Buehler test conducted comparable to guideline with acceptable restrictions is available, which is reliable with restrictions and adequate for classification and labelling purposes. Potency estimation is not mandatory when existing guideline and GLP conforming data are available, which were conducted before the new annex of the REACH Regulation entered into force. Moreover, no indication for skin sensitisation was observed in this study, thus, no dose response information is needed. For this reason and for reasons of animal welfare no additional LLNA was conducted.

Species:

guinea pig

Strain:

Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Weight at study initiation: Males (357-406 g); Females (381-452 g)
- Housing: 1-4 per cage (males separate from females) in suspended stainless steel cages with wire bottom
- Diet (e.g. ad libitum): Guinea Pig Diet #5025, PMI Feeds Inc., ad libitum
- Water (e.g. ad libitum): municipal tap water, ad libitum- Acclimation period: 5 d

ENVIRONMENTAL CONDITIONS
- Temperature: 72°F±5
- Humidity (%): 30-80
- Air changes (per hr): 10-12
- Photoperiod (hrs dark / hrs light): 12/12

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

100%

Day(s)/duration:

once weekly (on days 1, 8, 15); 6 h/d

Adequacy of induction:

other: non-irritant substance; pre-treatment not required for Buehler test

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

100%

Day(s)/duration:

on day 29; 6 h exposure

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

pretest: 4 (2 m / 2 f)main study: 10 (5 m/ 5 f)

Details on study design:

RANGE FINDING TESTS:
2 f and 2 m guinea pigs were selected for irritation screening to determine both the maximum dose producing no more than moderate irritation and the maximum nonirritating dose.
Tested concentrations: 100% (400 mg of test substance moistened with 300 µL deionized water), 75%, 50% and 25 % w/v concentrations of the test substance in deionised water.

MAIN STUDYA. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 h
- Test groups: test substance
- Control group: no treatment
- Site: lateral (left) from midline on the back
- Frequency of applications: once weekly (on days 1, 8, 15)
- Concentrations: 100%, moistened with deionised water

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 29
- Exposure period: 6 h
- Test groups: test substance
- Control group: test substance
- Site: virgin test site, laterally on the right rear quadrant of the exposure area
- Concentrations: 100%, moistened with deionised water
- Evaluation (hr after challenge): 24, 48

Challenge controls:

yes

Positive control substance(s):

yes

Remarks:

1-Chloro-2,4-dinitrobenzene

Positive control results:

positive reaction in 10/10 animals after 24 h and in 4/10 animals after 48 h

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

100%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

100%

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:

negative control

Dose level:

100%

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:

negative control

Dose level:

100%

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:

0.1% w/v solution in acetone

No. with + reactions:

10

Total no. in group:

10

No skin irritation was observed after 24 or 48 h in the irritation screening test at any concentration level. Body weight gain in the treated group was comparable to the negative control group.

Interpretation of results:

GHS criteria not met

Conclusions:

C16 Alkylamidopropyltrimethylammonium Chloride was not sensitising in this dermal sensitisisation study in guinea pig using the Buehler method.

Executive summary:

In a dermal sensitisation study comparable to OECD guideline 406 (17 July 1992) with C16 Alkylamidopropyltrimethylammonium Chloride (97.8% a.i.) 10 young adult Hartley guinea pigs were tested using the method of Buehler.

Test concentrations were selected based on the results of an irritation screening study: neither of the concentrations used in the pretest (100%, 75%, 50% and 25% w/v concentrations of the test substance in deionised water) produced skin irritation. Thus, in the main study 400 mg of the test substance moistened with 300 µL deionized water were used for epicutaneous induction and challenge.

After challenge no visible changes of the treated skin sites were observed in the test and control group animals 24 and 48 h after patch removal (= grade 0).

The positive control 1-Chloro-2,4-dinitrobenzene produced a sensitisation rate of 100%.

The test material produced a response in 0% of animals. According to CLP, EU GHS (Regulation (EC) No 1272/2008), a response of at least 15% of the test animals of an non-adjuvant type guinea pig test method for skin sensitisation is considered as positive.

C16 Alkylamidopropyltrimethylammonium Chloride is not a dermal sensitiser in this study.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

In a dermal sensitisation study comparable to OECD guideline 406 (17 July 1992) with C16 Alkylamidopropyltrimethylammonium Chloride (97.8% a.i.) 10 young adult Hartley guinea pigs were tested using the method of Buehler.

Test concentrations were selected based on the results of an irritation screening study: neither of the concentrations used in the pretest (100%, 75%, 50% and 25% w/v concentrations of the test substance in deionised water) produced skin irritation. Thus, in the main study 400 mg of the test substance moistened with 300 µL deionized water were used for epicutaneous induction and challenge.

After challenge no visible changes of the treated skin sites were observed in the test and control group animals 24 and 48 h after patch removal (= grade 0).

The positive control 1-Chloro-2,4-dinitrobenzene produced a sensitisation rate of 100%.

The test material produced a response in 0% of animals. According to CLP, EU GHS (Regulation (EC) No 1272/2008), a response of at least 15% of the test animals of a non-adjuvant type guinea pig test method for skin sensitisation is considered as positive.

C16 Alkylamidopropyltrimethylammonium Chloride is not a dermal sensitiser in this study.

 

Similar results were obtained with the structurally closely related read-across substance Stearic acid 3-(dimethylaminopropyl)amide:

In a dermal sensitisation study according to OECD TG 406, 1992) with Stearic acid 3-(dimethylaminopropyl)amide (a.i. > 99 %) in paraffinum perliquidum, young adult Dunkin-Hartley guinea pigs were tested using the Maximization test method. Positive control substance was mercaptobenzothiazole with a sensitisation rate of 70 %.

Mild to moderate skin reactions and necrosis were observed after intradermal induction (2.5 %) and dermal induction (1 %) in the test substance animals. After challenge exposure (2 %) no skin reactions were observed in test or control animals at any observation time. Therefore the sensitisation rate was 0%.

For the challenge concentration, which is the highest non-irritant dose, 2 % of the test item was used. The higher challenge concentration compared to the dermal induction concentration can be explained by the different exposure times, i.e. 48 hours for the dermal induction and 24 hours for the challenge.

In this study, Stearic acid 3-(dimethylaminopropyl)amide (a.i. > 99 %), is not a dermal sensitiser.

 

There is no information available for respiratory sensitisation. Therefore, there is a data gap in this respect. However, the data gap cannot be fulfilled with experimental data, since there is no internationally accepted animal model for respiratory sensitisation. In case human data for respiratory sensitisation emerges, this will be taken into account.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on relevant, reliable and adequate data, C16 Alkylamidopropyltrimethylammonium Chloride does not need to be classified and labelled according to Regulation (EC) No 1272/2008 with respect to skin sensitisation.