Amines, C16-18-alkyl, acetates

Endpoint summary

Description of key information

In a GLP compliant OECD TG 431 study, the test item was investigated for skin corrosive properties using the three-dimensional human skin model EpiDermTM, comprising a reconstructed epidermis with a functional stratum corneum. Based on the results, the test item is considered to be not corrosive to skin. In a follow-up study according to the OECD 439 study protocol, C16-18-(even numbered)alkylamine acetates was evaluated as being a skin irritant. This result is in line with data for the corresponding primary alkylamine C16-18-(even numbered)-alkylamines.
No study is available with regard to eye irritation. However, based on data from analogous primary alkylamines a high irritation potential to eyes has to be assumed.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2012-05-09 to 2012-05-11

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit, München, Germany

Test system:

human skin model

Amount/concentration applied:

solids: 25 µL DPBS + 25 mg

Duration of treatment / exposure:

60 +/- 1 minutes

Duration of post-treatment incubation (if applicable):

42 +/- 4 h

Number of replicates:

3

Species:

other: EpiDerm reconstructed human epidermis model (MatTek Corp.)

Details on test animals or test system and environmental conditions:

organotypic reconstructed three-dimensional model of the human epidermis

Type of coverage:

other: direct application

Controls:

other: three tissues for negative control (30µL DPBS) and positive control (30µL 5% SDS)

Details on study design:

3 replicate tissues are dosed with the test item, the negative control (DPBS) and the positive control (5% SDS), respectively. The tissues are incubated for 35 +/-1 minutes in a humidified incubator (37+/- 1 °C, 5 +/- 1% CO2, 95% RH) and further 25 minutes at room temperature. Then the test item and the controls are rinsed off with DPBS and the tissues are post-incubated for 24 +- 2 h and, after medium renewal, for further 18 +/- 2 h. Then the tissues are stained via MTT for 3 hours. Isopropanol extracts are measured photometrically at 550 nm.

Irritation / corrosion parameter:

other: other: mean relative tissue viability

Value:

> 50

Remarks on result:

other:

Remarks:

Basis: other: mean tissue viability of the negative control tissues. Time point: 60 min treatment 42 h post-incubation. Remarks: non-irritant; EU CLP and UN GHS: No Category. (migrated information)

Irritation / corrosion parameter:

other: other: mean relative tissue viability

Value:

<= 50

Remarks on result:

other:

Remarks:

Basis: other: mean tissue viability of the negative control tissues. Time point: 60 min treatment 42 h post-incubation. Remarks: irritant; EU CLP and UN GHS Category 2. (migrated information)

Interpretation of results:

other: irritant

Remarks:

Criteria used for interpretation of results: other: OECD 439

Conclusions:

The test item is classified as "irritant" (Category 2).

Executive summary:

In the in vitro skin irritation test using the EpiDerm human epidermis model 25 mg test item + 25 µL DPBS were applied topically for 60 minutes.

After 42 h post-incubation cytotoxic effects were determined via MTT reduction assay.

The mean relative tissue viability (% negative control) was <= 50%.

The test item is therefore classified as "irritant" (EU CLP and UN GHS: Category 2).

The test item showed irritant effects. The mean relative tissue viability (% negative control) was< 50% (30.6%) after 60 min treatment and 42 h post incubation. The test item could not be applied evenly on the tissue surface due to its waxy/jellylike consistence which formed clots after application. Therefore, the three tissues treated identically with the test item showed varying viabilities, whereas two replicates showed consistent values (17.2% and 22.0% versus 52.6%) indicating irritant potential. The standard deviation between the three tissues was therefore exceeding the 18% cut-off (19.2%). This is accepted due to the properties of the test item as described above.

This study is classified as acceptable:

Mean OD550 of the three negative control tissues is >=1 and <=2.5.

Mean relative tissue viability of the three positive control tissues is <= 20%.

Standard deviation (SD) of relative tissue viablity obtained from each three concurrently tested control tissues is < 18%.

This study satisfies the requirement for Test Guideline OECD 439 for in vitro skin irritation.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The registration substance was tested for skin irritation/corrosion in the in vitro human skin model tests according to OECD TG 431 and 439. Whereas no indication for skin corrosion was revealed, the test item demonstrated skin irritative properties. This is in line with experimental data from analogues primary alkylamines. With regard to eye irritation, no test data on the registration substance is available but data from analogous primary alkylamines indicate that it should be regarded as highly irritating to eyes.

Justification for selection of skin irritation / corrosion endpoint:
Guideline study according to GLP

Justification for selection of eye irritation endpoint:
No study for eye irritation is available for the registration substance. However, based on data from analoguous primary alkylamines a severe eye irritation potential has to be assumed.

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: highly irritating

Justification for classification or non-classification

Based on guideline conform testing, the registration substance has to be considered as a skin irritant and is therefore classified as "skin irritant category 2 with H315 - causes skin irritation" according to GHS-CLP (equivalent to EU Risk-Phrase R38 - irritating to skin according to DSD).

With regard to eye irritation, read-across to analogue primary alkylamines indicate that the registration substance is highly irritating to eyes and thus should be classified as causing serious damage to eyes (category 1, H318) according to GHS-CLP (equivalent to EU Risk-Phrase R41 - risk of serious damage to eyes).