Paraquat-dichloride

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20 Jun 2005 to 01 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 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

24 Apr 2002

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal 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

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 12 to 20 weeks
- Weight at study initiation: 3.47 to 3.89 kg
- Housing: individually housed in suspended cages, animals were 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 5 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

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

17 days

Number of animals:

3 female animals

Details on study design:

TEST SITE
- Area of exposure: approx 2.5 x 2.5 cm
- Type of wrap if used: cotton gauze patch. To prevent the animal interfering with the patch, the trunk of the rabbit was wrapped in an elasticated corset and the animal was returned to its cage for the duration of the exposure period.

REMOVAL OF TEST SUBSTANCE
Patch were removed from the animal and any residual test material removed by gentle swabbing with cotton wool soaked in 3% Teepol followed by warm tap water.

OBSERVATION TIME POINTS
- 1, 24, 48 and 72 hours after patch removal

SCORING SYSTEM:
- Method of calculation: the skin was scored according to the OECD scoring system (see table 1 in 'any other information on materials and methods incl. tables'). Mean values of scores from 24-48-72 hours per animal were taken for the classification. The interpretation of the results is based on table 2 in 'any other information on materials and methods incl. tables'.

ADDITIONAL OBSERVATIONS
- Body weight: at the start and at the end of the study
- Additional observations were made on Days 7, 10, 14 and 17 to assess the reversibility of skin reactions.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal: #1, #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 10 days

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 10 days

Results 3

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 10 days

Results 4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 5

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 10 days

Irritant / corrosive response data:

- Light brown coloured staining was noted at two treated skin sites during the study. The staining did not affect evaluation of skin responses.
- Well-defined erythema was noted at all treated skin sites one hour after patch removal and at the 24-hour observation. Well-defined erythema was noted at two treated skin sites and very slight erythema was noted at one treated skin site at the 48 and 72-hour observations. Very slight erythema was noted at all treated skin sites at the 7-day observation.
- Very slight oedema was noted at all treated skin sites one hour after patch removal. Very slight to slight oedema was noted at all treated skin sites at the 24 and 48-hour observations with very slight oedema at the 72-hour observation. Very slight oedema was noted at two treated skin sites at the 7-day observation.
- Loss of skin flexibility and/or elasticity were noted at two treated skin sites at the 48, 72-hour and 7-day observations. Moderate desquamation was noted at two treated skin sites at the IO-day observation. Reduced regrowth of fur was noted at one treated skin site at the 10 and 14-day observations.
- Treated skin sites appeared normal at the 10, 14 or 17-day observation.

Other effects:

Increased salivation was noted in two animals at the 48-hour observation and in one animal at the 72-hour observation. Bodyweight loss was noted in all animals at the 48-hour observation and in two animals at the 72-hour observation. One animal showed an increase in bodyweight at the 7-day observation.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In this OECD TG 404 study, the test substance was not determined to be irritating to the skin.

Executive summary:

The GLP compliant study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method was designed to meet the requirements of the following the OECD TG 404. A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced well-defined erythema and very slight to slight oedema. Other skin reactions noted were loss of skin elasticity and flexibility, moderate desquamation and reduced regrowth of fur. Treated skin sites appeared normal at the 10, 14 or 17-day observation. Bodyweight loss and increased salivation was noted in all animals. The mean value for erythema is determined to be 2 (max value for erythema score = 4) and the mean value for oedema is determined to be 1 (max value for oedema score = 4) in at least 2 out of 3 animals. The adverse effects are fully reversible within 10 days. The results indicate that the substance is not irritating to the skin.