1-[[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazole

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

11 Oct 2010 to 18 Oct 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

24 April 2002

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Version / remarks:

August 1998

Test guideline 3

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

April 29, 2004

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Commission Regulation (EC) No 440/2008, B.5 (L 142)

Version / remarks:

30 May 2008

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

1-[[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazole

EC Number:

262-104-4

EC Name:

1-[[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazole

Cas Number:

60207-90-1

Molecular formula:

C15H17Cl2N3O2

IUPAC Name:

1-{[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl}-1H-1,2,4-triazole

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age/weight at dosing: Approximately 13 weeks / 3116-3161 g
- Housing: Individually housed in metal wire rabbit cages
- Acclimatisation period: 12 days
- Diet: Lap gr. diet for rabbit; ad libitum
- Water: Tap water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 3°C
- Humidity: 30 - 70%
- Air changes: 15 - 20/hour
- Photoperiod: 12 hours of light/12 hours of dark

IN-LIFE DATES: 11 Oct 2010 to 18 Oct 2010

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount applied: A volume of 0.1 mL

Duration of treatment / exposure:

Single treatment

Observation period (in vivo):

1, 24, 48, 72 hours and 1 week following treatment

Number of animals or in vitro replicates:

3 animals

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: The eyes of the test animals were not washed out after application of test item.

OBSERVATIONS:
Assessment of ocular damage/irritation was made approximately 1, 24, 48, 72 hours and 1 week following treatment.
Additionally, to assess the presence of corneal damage, fluorescein staining was employed at the following time points after the standard observations have been made:
- At least 24 hours prior to instillation
- At 24 hours post dose
- All subsequent observation times points until Draize scores are zero
The duration of the observation period was sufficient to identify reversibility of changes. Any clinical signs of toxicity or signs of ill-health during the study were recorded.

SCORING SYSTEM:
Assessment of ocular damage/irritation was made approximately according to Draize J H (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.48 to 49).

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal: #1, #2 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

iris score

Basis:

animal: #1, #2 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 3

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal: #2 and #3

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 1 week

Results 4

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within: 1 week

Results 5

Irritation parameter:

conjunctivae score

Remarks:

(discharge)

Basis:

animal: #1, #2 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

3

Results 6

Irritation parameter:

chemosis score

Basis:

animal: #2 and #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 1 week

Results 7

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Conjunctival redness (score 1), discharge (score 2) and chemosis (score 1) were observed in all animals at the 1 hour observations. Chemosis (score 1) remained in two animals at the 48 hour observation. Conjunctival redness (scores 1/2) persisted in all animals at the 24- and 48- hour observations, and in two animals at the 72 hour observation. One week after treatment no further signs were observed and all local signs had fully reversed in all animals.
Two animals showed a positive fluorescein stain 24 hours after treatment, which was no longer observed at the 48 hour observation.

Other effects:

- No deaths occurred.
- No systemic signs of toxicity were noted during the study.
- The body weights of the rabbits were considered to be within the normal range of variability.
- Immediately following instillation, slight initial pain (2 on a 0-5 scale) was observed in all animals.
- No abnormal findings were observed in the cornea or iris of any animal at any of the measurement intervals.

Any other information on results incl. tables

Table 1. Eye irritation scores of test item according to the Draize scheme

Rabbit number and sex
	Male #1					Male #2					Male #3
Time after treatment (h)	1	24	48	72	1 wk	1	24	48	72	1 wk	1	24	48	72	1 wk
CORNEA E = Degree of Opacity F = Area of Cornea involved	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0
Score (E x F) x 5	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
IRIS D	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Score (D x 5)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
CONJUNCTIVAEA=Redness B = Chemosis C =Discharge	1 1 2	2 0 0	1 0 0	1 0 0	0 0 0	1 1 2	1 1 0	1 0 0	1 0 0	0 0 0	1 1 2	2 1 0	1 0 0	0 0 0	0 0 0
Score (A+B+C) x 2	8	4	2	2	0	8	4	2	2	0	8	6	2	0	0
Total Score	8	4	2	2	0	8	4	2	2	0	8	6	2	0	0

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In a primary eye irritation study performend in compliance with GLP and according to OECD 405 guideline the test substance is not an eye irritant.

Executive summary:

In a primary eye irritation study performed in compliance with GLP and according to OECD 405 guideline, 0.1 mL of the test substance was instilled into the conjunctival sac of the left eye of each of a group of three adult male New Zealand White rabbits. Immediately after instillation of the test material, an assessment of the initial pain reaction was made. Assessment of ocular damage/irritation was made approximately 1, 24, 48, 72 hours and 1 week following treatment, according to a numerical evaluation (Draize JH, 1977). Using the numerical data obtained a modified version of the system described by Kay JH and Calandra JC, 1962 was used to classify the ocular irritancy potential of the test material.

Slight initial pain was observed in all animals. Conjunctival redness, discharge and chemosis were observed in all animals at the 1 hour observations. Chemosis remained in two animals at the 48 hour observation. Conjunctival redness persisted in all animals at the 24- and 48- hour observations, and in two animals at the 72 hour observation. One week after treatment no further signs were observed and all local signs had fully reversed in all animals. Two animals showed a positive fluorescein stain 24 hours after treatment, which was no longer observed at the 48 hour observation. The study was terminated after the 1 week observation. No clinical signs of systemic toxicity were observed in the animals during this study. No intercurrent deaths occurred during this study. The body weights of all rabbits were considered to be within the normal range of variability.

The test substance is not an eye irritant.