Paraquat-dichloride

Endpoint summary

Description of key information

- The test substance is not considered to be irritating to the skin, based on the GLP compliant OECD TG 404 study.

- The test substance is considered to be irritating to the eyes based on the GLP compliant OECD TG 405 study.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

24 Apr 2002

Qualifier:

according to guideline

Guideline:

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

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Version / remarks:

Aug 1998

GLP compliance:

yes (incl. QA statement)

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

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.

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

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

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 10 days

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

24 Apr 2002

Qualifier:

according to guideline

Guideline:

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

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Version / remarks:

Aug 1998

GLP compliance:

yes (incl. QA statement)

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

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

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 17 days

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 24 days

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.

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation / corrosion

A GLP compliant study (Pooles, 2005) was performed to assess the irritation potential of the test material to the skin of the New Zealand White rabbit. The method was designed to meet the requirements of 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 was determined to be 2 (max value for erythema score = 4) and the mean value for oedema was determined to be 1 (max value for oedema score = 4) in at least 2 out of 3 animals. The adverse effects were fully reversible within 10 days. The results indicate that the substance is not irritating to the skin.

Eye irritation

A GLP study (Pooles, 2005) was performed to assess the irritation 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 on these results, the test substance was determined to be an irritant to the rabbit eye.

Justification for classification or non-classification

- Based on the available data, classification for skin irritiation is not warranted according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008. However, as the substance has a harmonised classification as Skin Irrit. 2 (H315: Causes skin irritation), this classification is adopted for this dossier.

- Based on the available data for eye irritation, the substance is classified as Eye Irrit. 2 (H319: Causes serious eye irritation), according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008. This classification is in line with the harmonised classification for this endpoint.