Benzenemethanamine, .alpha.,4-dimethyl-, (.alpha.R)-

Eye irritation

Administrative data

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: No guidline study, but conducted according to GLP.

Justification for type of information:

See chap. 13 read across justification

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: HET-CAM Test

Principles of method if other than guideline:

There are no official guidelines for the HET-CAM Test; however, the study was conducted
according to the following publications:
- Lüpke N.P. (1985): Hen’s Egg Chorio allantoic Membrane Test for Irritation Potential. Fd.
Chem. Toxic. 23, pp. 287 – 291.
- Spielmann, H. (1995): HET-CAM Test. In: Methods in Molecular Biology, 43 (eds.:
O’Hare, S. and Atterwill, C. K.) pp. 199 – 204.
- Spielmann, H. et al. (1996): Results of a Validation Study in Germany on Two In Vitro
Alternatives to the Draize Eye Irritation Test the HET-CAM Test and the 3T3 NRU
Cytotoxicity Test. ATLA 24, pp. 741 – 858.
In addition the study follows the testing strategy for determination of eye irritation/corrosion
as given in the following guideline:
- OECD Guideline for Testing of Chemicals No. 405, April 24, 2002 (“Acute Eye
Irritation/Corrosion”)

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

1-(3-methoxyphenyl)ethanamine

EC Number:

700-849-3

Cas Number:

62409-13-6

Molecular formula:

C9 H13 N O

IUPAC Name:

1-(3-methoxyphenyl)ethanamine

Details on test material:

The analyses of the test substance were carried out at the Analytical Department of BASF Aktiengesellschaft, Ludwigshafen, Germany.
Name of test substance: rac-1-(3-Methoxyphenyl)ethylamine
Test-substance No.: 06/0647-1
Batch identification: VSVU0019/VU0962 Fr 6 + Fr 8 LJ 8248/06
Purity: 99.3 area-% (analytical report No.: 06L00246)
Homogeneity: The test substance was homogeneous by visual inspection.
Storage stability: The stability under storage conditions over the study period was guaranteed by the sponsor, and the sponsor holds this responsibility.

ADDITIONAL TEST-SUBSTANCE INFORMATION
pH-value: ca. 7 (undiluted test substance); ca. 6 (10% preparation)

Test animals / tissue source

Species:

other: Chicken

Strain:

other: White Leghorn

Test system

Vehicle:

other: Olive oil Ph.Eur./DAB

Controls:

yes

Amount / concentration applied:

undiluted and 10% solution of the test substance in olive oil Ph.Eur./DAB

Duration of treatment / exposure:

A volume of 0.3 mL per egg of the liquid test substance / testsubstance solution was applied with a syringe and the CAM was observed until unambiguous irritation reactions were detected or up to a maximum time period of 3.5 minutes, respectively. It was possible to observe the reactions through the test substance/test-substance solution. The time until appearance of reactions was recorded.

Number of animals or in vitro replicates:

Number of eggs: 3 (undiluted test substance) and 3 (10% test-substance solution)

Results and discussion

In vitro

Results

Results 1

Remarks on result:

other: The undiluted test substance caused severe intravascular as well as extravascular coagulation and moderate haemorrhagia in all eggs within 9 – 12 seconds after application.

Results 2

Remarks on result:

other: The 10% test-substance solution in olive oil Ph.Eur./DAB caused moderate intravascular coagulation in all eggs after 49 – 85 seconds and moderate haemorrhagia in all eggs within 11 – 17 seconds.

Any other information on results incl. tables

The evaluation depends on the solubility of the test substance, the tested concentrations and the time until appearance of unambiguous intravascular coagulation of middle-sized vessels or extravascular coagulation of the treated CAM, respectively. The mean time until appearance of reaction over the eggs of a treatment group was calculated (mean time to coagulation = mtc in seconds):

mtc(100%) < 90 "risk of serious damage to the eyes"

or

mtc(100%) x 0.019 + mtc(10%) x 0.017 < 4.404 "risk of serious damage to the eyes"

mtc(100%) ≥ 90 "no risk of serious damage to the eyes"

Grading

0 No visible change

1 Slight reaction

2 Moderate reaction

3 Severe reaction

Applicant's summary and conclusion

Conclusions:

Based on the results of this study it was concluded, that rac-1-(3-Methoxyphenyl)ethylamine caused serious eye damage in the HET-CAM Test under the test conditions.

Executive summary:

The potential of rac-1-(3-Methoxyphenyl)ethylamine to cause serious damage to the eyes/mucous membranes was assessed by a single topical application of 0.3 mL of the undiluted test substance and 0.3 mL of a 10% test-substance solution in olive oil Ph.Eur./DAB, to the chorionallantoic membrane (CAM) of fertilized and incubated hen eggs. Three eggs per test-substance concentration were observed until unambiguous irritation reactions were detected or up to a maximum time period of 210 seconds. The occurrence of vascular injury or intravascular coagulation in response to the test substance was recorded. The undiluted test substance caused severe intravascular as well as extravascular coagulation and moderate haemorrhagia in all eggs within 9 – 12 seconds after application. The 10% test substance solution in olive oil Ph.Eur./DAB caused moderate intravascular coagulation in all eggs after 49 – 85 seconds and moderate haemorrhagia in all eggs within 11 – 17 seconds. Based on the results of this study it was concluded, that rac-1-(3-Methoxyphenyl)ethylamine causes serious eye damage in the HET-CAM Test under the test conditions.