Paraquat-dichloride

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

15 Jun 2005 to 20 Jul 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

24 Apr 2002

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Version / remarks:

Aug 1998

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Paraquat-dichloride

EC Number:

217-615-7

EC Name:

Paraquat-dichloride

Cas Number:

1910-42-5

Molecular formula:

C12H14N2.2Cl

IUPAC Name:

1,1’-dimethyl-4,4’-bipyridyldiylium dichloride

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: 12 to 20 weeks old
- Weight at study initiation: 3.34 kg
- Housing: the animal was housed in a suspended metal cage, provided with environmental enrichment items which were considered not to contain any contaminant of a level
- Diet: free access to food, Certified Rabbit Diet (Code 5322)
- Water: free access to mains drinking water
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23
- Humidity (%): 30 to 70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

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

Duration of treatment / exposure:

Single application of the test substance

Observation period (in vivo):

35 days

Number of animals or in vitro replicates:

1

Details on study design:

APPLICATION OF TEST SUBSTANCE
A volume of 0.1 mL of the test substance was placed into the conjunctivae sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after treatment, to prevent loss of the test material, and then released.

REMOVAL OF TEST SUBSTANCE
- Washing: no

SCORING SYSTEM:
- Method of calculation: the eye damage was scored according to the Draize scale scoring system (see Table 1 in 'any other information on materials and methods incl. tables').
- Assessment of ocular damage/irritation: immediately after administration of the test substance and in 1; 24; 48; 72 hours after treatment
- Additional observations to assess the reversibility of the ocular effects: on Days 7, 10, 14, 17, 21, 24, 28, 31 and 35

TOOL USED TO ASSESS SCORE:
- light source from a standard ophthalmoscope

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 17 days

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 24 days

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 35 days

Irritant / corrosive response data:

- Scattered or diffuse corneal opacity was noted in the treated eye at the 14-day observation and at all subsequent observations.
- Vascularisation, with a localised ingrowth of vessels for 2 to 3 mm, was noted in the treated eye at the 14 and 17-day observations. Vascularisation, with a localised ingrowth of vessels for 4 to 5 mm, was noted in the treated eye at the 21-day observation. Vascularisation, with a localised ingrowth of vessels for 2 to 3 mm, was noted in the treated eye at the 24-day observation and at all subsequent observations.
- Iridial inflammation was noted in the treated eye one hour after treatment and at the 24, 48, 72-hour, 7, 10 and 14-day observations.
- Moderate conjunctival irritation was noted in the treated eye one hour after treatment and at the 24, 48, 72-hour, 7, 10 and 14, 17, and 21-day observations. Minimal conjunctival irritation was noted in the treated eye at the 24, 28, 31 and 35-day observations.
- Alopecia was noted around the treated eye at the 14, 17, 21 and 24-day observations.
- The vascularisation observed at the 14-day observation was still present at the end of the observation period on Day 35.

Other effects:

Increased salivation was noted in the animal at the 7 and 10-day observations. Bodyweight loss was noted in the animal at the 7-day observation. The animal's bodyweight was monitored and was still underweight at the 14-day observation.

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

In this OECD TG 405 study, the test substance was determined to be irritating to the eyes

Executive summary:

The GLP study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The method was designed to meet the requirements of the OECD TG 405. A single application of the test material to the non-irrigated eye of one rabbit produced scattered or diffuse corneal opacity, iridial inflammation and moderate conjunctival irritation. Vascularisation, with a localised ingrowth of vessels for up to 4 to 5 mm, was noted in the treated eye. Alopecia was noted around the treated eye. Increased salivation and bodyweight loss were also noted during the study. The mean (24 -72 hours) irritation scores were determined to be 0, 1, 2 and 2 for corneal opacity, iritis, conjuctival redness and chemosis, respectively. In addition, vascularisation of the cornea was observed at the 14-day observation and was still present at the end of the observation period on Day 35.Due to the severity of the response produced in this one animal, no further animals were treated.Based these results, the test substance was determined to be an irritant to the rabbit eye.