N-(carboxymethyl)-3-[(2Z)-docos-2-enoylamino]-N,N-dimethylpropan-1-aminium

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 30 October 2002 to 19 November 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline-conform study under GLP without deviations

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Details on test material:

- Name of test material (as cited in study report):DV6850
- Substance type: powder
- Physical state: solid
- Analytical purity: 83.7%
- Lot/batch No.: R0332-52C
- Expiration date of the lot/batch: 2003/09/30
- Storage condition of test material: ca 4°C in the dark in dry conditions

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Highgate Farm, Market Rasen, Lincolnshire, England
- Age at study initiation: >= 8 weeks
- Weight at study initiation: 3.12 - 3.60 kg
- Housing: individually in stainless steel cages with perforated floors
- Diet (e.g. ad libitum): 125 g/d of a standard laboratory diet (Special Diet Services STANRAB (P) SQC pellet), dietary supplement of hay until at least two days prior to dose instillation
- Water (e.g. ad libitum): ad libitum
- Acclimation period: >= 13 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15-23°C until 4 November 2002, thereafter 16-20°C
- Humidity (%): 40-70%
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12 hours of continuous artificial light in each 24 hour period

IN-LIFE DATES: From: To:

Test system

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL weighing approximately 100 mg

Duration of treatment / exposure:

single instillation

Observation period (in vivo):

4 days

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
The substance was not removed.

SCORING SYSTEM:
See Table 1 and Table 2 in "Any other information on materials and methods incl. tables"

TOOL USED TO ASSESS SCORE: An ophthalmoscope and a pencil beam torch were used to facilitate inspection of the eyes.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Remarks:

corneal opacity

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 2

Irritation parameter:

iris score

Remarks:

Iridal lesions

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 3

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

mean

Time point:

24/48/72 h

Score:

0.7

Max. score:

1

Reversibility:

fully reversible within: 3 days

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritant / corrosive response data:

A crimson-red conjunctival appearance, very-slight discharge and in two cases very-slight chemosis were apparent one hour after instillation. Injection of the conjunctival blood vessels was evident in all animals 24 and 48 hours later; all animals were overtly normal 72 hours after instillation.

Other effects:

There was no sign of toxicity or ill health in any rabbit during the observation period.

Any other information on results incl. tables

Table 1 - Grades for ocular irritation responses following instillation of DV6850

Animal number and sex: 4674 M			Pain evaluation response: 2
Region of the eye	Response		Grade of response at time after instillation Hours
			1	24		48	72
Cornea	Opacity		0	0		0	0
	Area		0	0		0	0
	Ulceration		-	-		-	-
	Stippling		-	-		-	-
Iris	Value		0	0		0	0
Conjunctiva	Redness		2	1		1	0
	Chernosis		0	0		0	0
	Discharge		1	0		0	0
	Necrosis		-	-		-	-
	Ulceration		-	-		-	-
Animal number and sex: 4733 M			Pain evaluation response: 2
Region of the eye		Response	Grade of response at time after instillation Hours
			1	24		48	72
Cornea		Opacity	0	0		0	0
		Area	0	0		0	0
		Ulceration	-	-		‑	-
		Stippling	-	-		-	-
Iris		Value	0	0		0	0
Conjunctiva		Redness	2	1		1	0
		Chemosis	0	0		0	0
		Discharge	1	0		0	0
		Necrosis	-	-		-	-
		Ulceration	-	-		-	-
Animal number and sex: 4734 M			Pain evaluation response: 2
Region of the eye	Response		Grade of response at time after instillation Hours
			1	24	48			72
Cornea	Opacity		0	0	0			0
	Area		0	0	0			0
	Ulceration		-	-	-			-
	Stippling		-	-	-			-
Iris	Value		0	0	0			0
Conjunctiva	Redness		2	1	1			0
	Chemosis		1	0	0			0
	Discharge		1	0	0			0
	Necrosis		-	-	-			-
	Ulceration		-	-	-			-

Classification Criteria

The study protocol indicated that the criteria regarding classification, packaging and labelling of dangerous substances of the European Communities as outlined in Directive 93/21/EEC would be employed. However, the updated criteria as documented in 2001/59/EC was employed.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

DV6850 does not require classification as an eye irritant.

Executive summary:

A study was performed to assess the eye irritation potential of DV6850 to the rabbit. The methods followed were that described in EEC Methods for the determination of toxicity, Annex to Directive 92/69/EEC (Official Journal No. L383A, 29.12.92), Part B. Method B.5, acute toxicity (eye irritation), OECD Guideline for the Testing of Chemicals No. 403, "Acute Eye Irritation/Corrosion", adopted 24 February 1987 and EPA Health Effects Test Guidelines OPPTS 870.2400 Acute Eye Irritation EPA 712-C-98-195, August 1998.

Three rabbits were each administered a single ocular dose of a volume of 0.1 mL of the test substance weighing approximately 100 mg and observed for four days after instillation.

A crimson-red conjunctival appearance, very-slight discharge and in two cases very-slight chemosis were apparent one hour after instillation. Injection of the conjunctival blood vessels was evident in all animals 24 and 48 hours later; all animals were overtly normal 72 hours after instillation. Instillation of the test substance gave rise to slight initial pain response. Mean individual scores at 24, 48 and 72 h after application were 0.7, 0.7, 0.7 for conjunctival redness, for rabbits No. 1, 2, 3, respectively, and 0.0 for all other ocular parameters.

DV6850 does not require classification as an eye irritant, according to the criteria of DSD (Directive 67/548/EEC) or CLP (Regulation (EC) 1272/2008).