A mixture of: N,N-diethylpropane-1,3-diamine 6-methyl-2-(4-(2,4,6-triaminopyrimidin-5-ylazo)phenyl)benzothiazole-7-sulfonate; 2,2-iminodiethanol 6-methyl-2-(4-(2,4,6-triaminopyrimidin-5-ylazo)phenyl)benzothiazole-7-sulfonate; 2-methylaminoethanol 6-methyl-2-(4-(2,4,6-triaminopyrimidin-5-ylazo)phenyl)benzothiazole-7-sulfonate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to the OECD TG 405 and followed GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

(1987)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

A mixture of: N,N-diethylpropane-1,3-diamine 6-methyl-2-(4-(2,4,6-triaminopyrimidin-5-ylazo)phenyl)benzothiazole-7-sulfonate; 2,2-iminodiethanol 6-methyl-2-(4-(2,4,6-triaminopyrimidin-5-ylazo)phenyl)benzothiazole-7-sulfonate; 2-methylaminoethanol 6-methyl-2-(4-(2,4,6-triaminopyrimidin-5-ylazo)phenyl)benzothiazole-7-sulfonate

EC Number:

403-410-1

EC Name:

A mixture of: N,N-diethylpropane-1,3-diamine 6-methyl-2-(4-(2,4,6-triaminopyrimidin-5-ylazo)phenyl)benzothiazole-7-sulfonate; 2,2-iminodiethanol 6-methyl-2-(4-(2,4,6-triaminopyrimidin-5-ylazo)phenyl)benzothiazole-7-sulfonate; 2-methylaminoethanol 6-methyl-2-(4-(2,4,6-triaminopyrimidin-5-ylazo)phenyl)benzothiazole-7-sulfonate

Cas Number:

114565-65-0

Molecular formula:

C18 H16 N8 O3 S2 . x C7 H18 N2 . x C4 H11 N O2 . x C3 H9 N O

IUPAC Name:

(3-aminopropyl)diethylamine; 2-(methylamino)ethan-1-ol; 2-[(2-hydroxyethyl)amino]ethan-1-ol; 6-methyl-2-{4-[2-(2,4,6-triaminopyrimidin-5-yl)diazen-1-yl]phenyl}-1,3-benzothiazole-7-sulfonic acid

Details on test material:

- Name of test material (as cited in study report): FAT 11'184/B
- Physical state: powder
- Analytical purity: No data mentioned in the report. However, in an Ames test report (CCR 124312, see IUCLID chapter 7.6.1) using the same batch of test substance the analytical purity was given as 89.6%.
- Lot/batch No.: Op. 1 BD 823/8
- Expiration date of the lot/batch: January, 1993
- Stability under test conditions: test substance in dilution is stable for at least 2 hours

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Designation: New Zealand White, KFM (SPF-Quality)
- Source: Kleintierfarm Madoerin AG, CH 4414 Fuellinsdorf / Switzerland
- Age at study initiation: 14 - 15 weeks
- Weight at study initiation: 3 - 3.1 kg
- Housing: individually in stainless steel cages with automatic cleaning and drinking system
- Diet: Pelleted standard Kliba 341, Batch 32/87 rabbit maintenance diet, ad libitum
- Water: tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 40 - 70
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated eye served for control

Amount / concentration applied:

The test article was applied undiluted (0.1 g per animal) in the conjunctival sac of the left eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test article.

Duration of treatment / exposure:

The treated eyes were not rinsed; the first examination was done one-hour after instillation of the test article in the conjunctival sac. Further examinations were conducted after 24, 48 and 72 hours, 7, 14 and 21 days following treatment.

Observation period (in vivo):

The observation was terminated 21 days after administration of the test article. All rabbits were then sacrificed and discarded.

Number of animals or in vitro replicates:

Three animals (one male and 2 females) were used.

Details on study design:

The irritation was assessed according to the OECD guideline and the findings were scored according to the numerical Draize scoring system.
Eye examinations were made with a slit-lamp 30 SL (C. Zeiss AG, Zuerich / Switzerland) and a Varta Cliptrix diagnostic-lamp (A. Riegger, Basel / Switzerland).

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: mean over 24, 48 and 72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 21 days

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: mean over 24, 48 and 72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 21 days

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

other: mean over 24, 48 and 72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 4

Irritation parameter:

iris score

Basis:

animal: 1, 2 and 3, respectively

Time point:

other: mean over 24, 48 and 72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility: not applicable

Remarks on result:

other: no effects seen in the iris

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: mean over 24, 48 and 72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 14 days

Results 6

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: mean over 24, 48 and 72 h

Score:

1.7

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: mean over 24, 48 and 72 h

Score:

1.7

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 8

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: mean over 24, 48 and 72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 9

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: mean over 24, 48 and 72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 10

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: mean over 24, 48 and 72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritant / corrosive response data:

In animal 1, corneal opacity graded 1 was seen at reading time point (RTP) 72 h, 7 d and 14 d; conjunctival redness graded 2 was seen at RTP 1, 24, 48 and 72h, and had turned slight (grade 1) on 7d; thereafter no redness was evident; chemosis was graded 2 at RTP 1 h and 1 thereafter, at RTP 24, 48 and 72 h. The iris was inconspicuous. Discharge reaching from severe to slight was observed until RTP 14 d whereas an orange discoloration of the eye lasted until RTP 7 days. Complete reversibility of all findings was attained after 21 days.
In animal 2, corneal opacity graded 1 was seen at reading time point (RTP) 24 h, 48 h, 72 h, 7 d and 14 d; conjunctival redness graded 2 was seen at RTP 1, 24, 48 h, and had turned slight (grade 1) at 72 h; thereafter no redness was evident; chemosis was graded 2 at RTP 1 h and 1 thereafter, at RTP 24 and 48 h. The iris was inconspicuous. Discharge reaching from severe to slight was observed until RTP 48 h whereas an orange discoloration of the eye lasted until RTP 7 days. Complete reversibility of all findings was attained after 21 days.
In animal 3, corneal opacity graded 1 was seen at reading time point (RTP) 72 h and 7 d; conjunctival redness graded 2 was sen at RTP 1, 24, 48 h, and had turned slight (grade 1) at 72 h; thereafter no redness was evident; chemosis was graded 2 at RTP 1 h and 1 thereafter, at RTP 24 and 48 h. The iris was inconspicuous. Discharge reaching from severe to slight was observed until RTP 48 h whereas an orange discoloration of the eye lasted until RTP 7 days. Complete reversibility of all findings was attained after 14 days.

Other effects:

Discharge, initially severe becoming slight in the course of time, was seen in all 3 animals (animal 1 until day 14, animal 2 until 48 h, animal 3 until 48 h).
In the area of application a orange staining of the cornea and conjunctivae by pigment or coloring of the test article was observed, which lasted for 7 days in each of the 3 animals.
No acute toxic symptoms were observed in the animals during the test period, and no mortality occurred.The body weight gain of all rabbits was similar.

Any other information on results incl. tables

Eye Finding (Scoring according to Draize):

Animal 1
Reading time point	Eye Findings (Scoring according to Draize)
	Cornea opacity	Iris	Conj. Redness	Chemosis	Discharge	Discoloration
1 h	0	0	2	2	severe	yes
24 h	0	0	2	1	severe	yes
48 h	0	0	2	1	severe	yes
72 h	1	0	2	1	slight	yes
7 d	1	0	1	0	slight	yes
14 d	1	0	0	0	slight	none
21 d	0	0	0	0	none	none
Animal 2
Reading time point	Eye Finding (Scoring according to Draize)
	Cornea opacity	Iris	Conj. Redness	Chemosis	Discharge	Discoloration
1 h	0	0	2	2	severe	yes
24 h	1	0	2	1	moderate	yes
48 h	1	0	2	1	slight	yes
72 h	1	0	1	0	none	yes
7 d	1	0	0	0	none	yes
14 d	1	0	0	0	none	none
21 d	0	0	0	0	none	none
Animal 3
Reading time point	Eye Finding (Scoring according to Draize)
	Cornea opacity	Iris	Conj. Redness	Chemosis	Discharge	Discoloration
1 h	0	0	2	2	severe	none
24 h	0	0	2	1	moderate	yes
48 h	0	0	2	1	slight	yes
72 h	1	0	1	0	none	yes
7 d	1	0	0	0	none	yes
14 d	0	0	0	0	none	none
21 d	0	0	0	0	none	none

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified