1,2-Propanediamine, N1-(2-aminoethyl)-3-(4-ethoxyphenyl)-, hydrochloride (1:2), (2S)-

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from March to April 96

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

only one animal tested with severe irritating findings

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

24 February 1987

Deviations:

yes

Remarks:

despite of reversibility of effects no further animals tested to confirm irritation

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

(S)-1-(4-Ethoxybenzyl)-3-azapentane-1,5-diaminedihydrochloride

EC Number:

606-947-1

Cas Number:

221640-21-7

Molecular formula:

C13 H23 N3 O . 2 Cl H

IUPAC Name:

(S)-1-(4-Ethoxybenzyl)-3-azapentane-1,5-diaminedihydrochloride

Test material form:

solid

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Schriever
- body weight: 2.9 kg
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 18 days
- Identification: tattoo numbers in the ear

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- rel. Humidity (%): 52 - 58
- Photoperiod (hrs dark / hrs light): 12 / 12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: the left eye, which remained untreated, served as control.

Amount / concentration applied:

0.1 mL (corresponded to 51 mg substance)

Duration of treatment / exposure:

test substance remained in the eye (eye was not rinsed)

Observation period (in vivo):

13 days

Number of animals or in vitro replicates:

1 male- since severe intolerance reactions occurred in this animal, the other animals originally foreseen for this study were not exposed to the substance for humane reasons.

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no washing

SCORING SYSTEM: According to Annex to EEC Directive 92/69/EWG, dated 31. Jul. 92, for the 17th adaptation of the EEC Directive 67/548/EWG, B. 5 Acute Toxicity (Eye irrtation) Off J EEC, L383, Luxembourg, 29 Dec. 92.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Reversibility:

other: not applicable

Remarks on result:

not measured/tested

Remarks:

Chemosis refers to reddening of the eye lids and nictating membranes, only reddening of the conjunctivae was measured.

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 3

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 4

Irritation parameter:

conjunctivae score

Remarks:

reddening

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

3

Results 5

Irritation parameter:

conjunctivae score

Remarks:

swelling

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Any other information on results incl. tables

Summary of local findings after single application of the test substance in the rabbit eye

Findings	Right eye 0.1 mL test item/eye; animal: 696M
	A	X-Y
Outer eyelids
secretion with wetting of surrounding fur
+	1	1-1
++	2	1-2
+++	1	1-1
swelling of the edge of the eyelids (clue to severely edematous
(+)	1	7-7
swelling of conjunctiva palpebrae)
+	6	2-8
+++	3	1-1
reddening of the skin of the eyelids
(+)	1	7-7
+	7	1-9
++	3	1-3
incomplete eyelid closure
+	4	1-2
dacryorrhea, red-coloured	1	1-1
incrustation of secretoryproduct at the fur around the eye	5	2-6
red-coloured incrustation of secretory product at the fur around the eye	3	3-5
Conjunctiva palpebrae
reddening
(x)	2	11-12
+	2	9-10
++	5	4-8
+++	5	1-3
swelling, partly edematous
(+)	2	9-10
+	6	3-8
++	1	2-2
+++	3	1-1
injection of blood vessels
+	2	11-12
++	4	7-10
+++	8	1-6
hemorrhage
+	3	4-6
Membrana nicitans
reddening
+	2	7-8
++	8	1-6
swelling (partly edematous)
+	3	4-6
++	2	2-3
+++	3	1-1
injection of blood vessels
+	2	11-12
++	4	7-10
+++	7	1-6
hemorrhage
++	7	2-8
not visible due to bleeding of the mucosa	1	2-2
mucosa partly whitish	6	7-12
Conjunctiva sclerae
reddening
+	1	2-2
injection of blood vessels
+	4	3-8
++	1	2-2
could not be assessed due to the severe swelling of the conjunctiva palpebrae	3	1-1
injection of blood vessels
+	4	3-8
++	1	2-2
Cornea
opacity
+	3	1-1
bluntness
+	3	1-1
Iris
Iris only partly visible	3	1-1

A = summation of positive findings

x-y = first-last day of occurrence of a finding

(+) = very slight, + = slight, ++ = moderate, +++ = severe

 

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

In a local tolerance test on the rabbit eye according to OECD TG 405 in the initial test using one animal a single application of the test substance into the conjunctival sac provoked severe irritation which gradually subsided during the course of the 13 days observation period. The other animals originally foreseen for this study were not exposed to the substance for animal welfare reasons.
Despite of the reversibility of the effects the investigation of only one animal in this study is limitating the assessment. Since the structural analogue Z-Triamin-Dihydrochloride (CAS 221640-14-8) was found to be corrosive to the eye in a BCOP test (OECD TG 437) also for the Triamine-Dihydrochloride (CAS 221640-21-7) severe eye damage (corrosion) cannot be excluded.

Executive summary:

In a primary eye irritation study similar to OECD TG 405, 0.1 mL corresponding to 51 mg of Triamine Dihydrochloride was instilled into the conjunctival sac of the right eye of a young adult male New Zealand White rabbit and the animal was observed for 14 days. The eyes were not washed. Irritation was scored by the method described in the guideline.

A single application of 0.1 mL of the test substance into the conjunctival sac of the rabbit eye led to slight to severe secretion, reddening and swelling of the outer eyelids, moderate but predominantly severe reddening, swelling and vascular injection of the conjunctivae, incomplete eyelid closure accompanied by ectropium as well as slight opacity of the cornea on the application day. Moderate to severe reddening and vascular injection and slight to moderate swelling of the conjunctivae accompanied by hemorrhage into the mucous membrane of the conjunctivae were observed up to day 6. Afterwards the findings gradually subsided and had disappeared by day 13. With regard to the observed effects in this study, the test item is considered to be a severe eye irritant.