trans-(5RS,6SR)-6-amino-2,2-dimethyl-1,3-dioxepan-5-ol

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

June 1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: Beckley, J.H.; Comparative eye testing: Man vs. animal. Toxicol. Appl. Pharmacol. 7, 93- 101, 1965

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

trans-(5RS,6SR)-6-amino-2,2-dimethyl-1,3-dioxepan-5-ol

EC Number:

419-050-3

EC Name:

trans-(5RS,6SR)-6-amino-2,2-dimethyl-1,3-dioxepan-5-ol

Cas Number:

79944-37-9

Molecular formula:

C7H15NO3

IUPAC Name:

6-amino-2,2-dimethyl-1,3-dioxepan-5-ol

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Schriever
- Weight at study initiation: male: 3.5 kg; females: not weighed at the start of the study; at the end of the test: 4.6 kg
- Housing: individually under conventional conditions in metal cages
- Diet (e.g. ad libitum): ad libitum; pell. Altromin® K
- Water (e.g. ad libitum): ad libitum; demineralized water and acidificed water
- Acclimation period: > 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-21
- Humidity (%):54-70
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg/eye

Observation period (in vivo):

11 days

Number of animals or in vitro replicates:

1 males and 2 females

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): None

SCORING SYSTEM: according to the score system in the "lllustrated Guide for Grading Eye Irritation by Hazardous Substances“, U.S. Department of Health, Education and Welfare, Food and Drug Administration, Washington D.C. 20204, USA.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.55

Max. score:

4

Reversibility:

fully reversible within: 1d

Results 2

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

2.2

Max. score:

3

Reversibility:

fully reversible within: 9-11d

Results 3

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 4

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Any other information on results incl. tables

Evaluation of the local tolerance of the test item on the rabbit conjunctiva after a single application according to the score system in the "Illustrated Guide for Grading Eye Irritation by Hazardous Substances", U.S. Department of Health, Education and Welfare, Food and Drug Administration Washington D. C. 20204, USA

Animal number/sex			Hours after application			Results
			24	48	72
851M	Cornea		0	0	0	+
	Iris		0	0	0
	Conjunctiva	Reddening	2+	2+	2+
		swelling	3+	0	0
808 F	Cornea		0	0	0	+
	Iris		0	0	0
	Conjunctiva	Reddening	3+	2+	2+
		swelling	1	0	0
772F	Cornea		0	0	0	+
	Iris		0	0	0
	Conjunctiva	Reddening	3+	2+	2+
		swelling	1	0	0

 

Findings	Right eye		Left eye
	100 mg test item/eye (one male, two females)		untreated
	A/B	(x-y)
Outer eyelids			Without findings
Secretion with wettening of surrounding fur
Slight	3/2	(1-2)
Moderate	3/3	(1-2)
severe	5/3	(1-1)
Swelling of the margin of eyelids
Slight	2/1	(2-3)
Reddening of the skin of eyelids
Slight	6/2	(1-3)
Moderate	3/2	(1-1)
Complete eyelid closure	3/3	(1-2)
Incomplete eye lid closure	5/3	(1-2)
Conjunctiva palpebrae superior et inferior
Hematomas (conj. Inferior)
Slight (Ø 1 mm)	2/2	(5-10)
Moderate (Ø 2 mm)	2/1	(8-9)
Severe (Ø 3 mm)	9/1	(1-7)
Reddening
Slight	9/3	(5-8)
Moderate	12/3	(1-4)
severe	6/3	(1-2)
Swelling
Slight	2/2	(2-2)
moderate	8/3	(1-1)
Injection of blood vessels
Slight	1/1	(1-1)
Moderate	11/3	(1-6)
Membrana nicitans
Reddening
Slight	20/3	(1-10)
Moderate	4/3	(2-3)
Swelling
Slight	4/3	(1-2)
moderate	8/3	(1-1)
Injection of blood vessels
Slight	6/3	(1-9)
Moderate	16/3	(2-8)
Severe	1/1	(2-2)
Conjuntiva sclerae
No details visible due to swellings of conjunctiva palpebrae	6/3	(1-1)
Reddening
Slight	2/1	(1-1)
Injection of blood vessels
Slight	2/1	(1-1)
moderate	1/1	(1-1)
A=summation of positive findings B=number of animals concerned X=first day of occurrence of a finding Y= last day of the occurrence of a finding

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

According to the score system in the "Illustrated Guide for Grading Eye Irritation by hazardous Substances“ all animals reacted positively.

Executive summary:

In a primary eye irritation study similar to OECD test guideline 405, 100 mg of Aminodioxepan (100% a.i.) was instilled into the conjunctival sac of the right eye of young adult New Zealand White rabbits, one male and two females. Animals then were observed for 11 days.  Irritation was scored by the method cited in  the "lllustrated Guide for Grading Eye Irritation by Hazardous Substances“, U.S. Department of Health, Education and Welfare, Food and Drug Administration, Washington D.C. 20204, USA.

On the day of application, severe secretions, wettening of the external skin of the eyelids, reddenings of the eyelids (slight to moderate) and conjunctivae (moderate to severe), swellings of the conjunctivae (moderate) as well as vascular injections of the conjunctivae and eyelid closure occurred in all animals. From the second or third day onwards the majority of the findings, with the exception of the conjunctival vascular injections (mainly moderate up to day 6 or 8, respectively), gradually faded away. In addition, a hemorrhage was observed in 2 animals starting on day 1 or day’ 5, respectively (maximally 3 mm e) in the conjunctiva inferior (identified in table 2 as hematoma). Only one animal had a swelling of the eyelid margin on days 2 and 3 (slight). The animals were free of findings from day 11 (nos. 772F, 851M) and day 9 (no. 808F) onwards.

The control eyes were without findings. In this study, Aminodioxepan is moderately irritating to the eye based on the classification by Regulation (EC) No. 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS) Category 2 (irritating to eyes).