Paraquat-dichloride

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

14 Jun 2005 to 28 June 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 402 (Acute Dermal Toxicity)

Version / remarks:

Adopted 24 February 1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

Commission Directive 92/69/EEC

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

August 1998

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Safepharm Laboratories Limited, Shardlow, Derbyshire, DE72 2GD, UK

Test type:

standard acute method

Limit test:

yes

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:

rat

Strain:

Sprague-Dawley

Remarks:

CD (Crl: CD (SD) IGS BR)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: at least 200 g, weight variations per sex < 20%
- Housing: the animals were housed in suspended solid-floor polypropylene cages furnished with woodflakes. The animals were housed individually throughout the study.
- Diet: ad libitum to Certified Rat and Mouse Diet (Code 5LF2)
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25
- Humidity (%): 30 to 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: shorn skin on the back and flanks of the animals
- % coverage: 10 (total body surface area)
- Type of wrap if used: surgical gauze semi-occluded with a piece of self-adhesive bandage

REMOVAL OF TEST SUBSTANCE
- Washing: 3% Teepol followed by warm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount applied: 2000 mg/kg
- Constant volume or concentration used: yes (1.77 mL/kg undiluted test substance)

Duration of exposure:

24 hours

Doses:

Dose level 2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: signs of toxicity: ½, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days. Body weight: individual body weights were recorded prior to application of the test material on day 0 (defined as day before exposure) and on days 7 and 14.
- Necropsy of survivors: At necropsy (after cervical dislocation) external examination and opening of the abdominal and thoracic cavities was performed.
- Other examinations performed: After removal of the dressings and subsequently once daily for fourteen days, the test sites were examined for evidence of primary irritation and scored according to the following scale from Draize.

Statistics:

Using the mortality data obtained, an estimate of the acute dermal median lethal dose (LD50) of the test material was made.

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: original value presented in study

Effect levels 2

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 922 mg/kg bw

Based on:

test mat.

Remarks on result:

other: recalculated value, expressed as pure substance, see ‘any other information on results incl. tables’ for respective calculation

Mortality:

No mortality observed

Clinical signs:

other: No signs of systemic toxicity

Gross pathology:

No abnormalities were noted at necropsy

Other findings:

- Dermal Reactions: Very slight to well-defined erythema was noted at the treatment sites of three males and all females. Other signs of dermal irritation noted were haemorrhage of dermal capillaries, crust formation, small superficial scattered scabs and glossy skin. Skin reactions prevented evaluation of erythema and oedema at the treatment sites of two females during the study.

Any other information on results incl. tables

Calculation of key result

The doses of the test substance were expressed in technical paraquat dichloride, which relates to an aqueous solution of the registered substance. The key effect levels are calculated by correction for the amount of water: 0.461x 2000 mg paraquat dichloride technical material / kg bw = 922 mg pure paraquat dichloride / kg bw

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The LD50 for pure test substance (recalculated value) was determined to be >922 mg/kg body weight for males/females. This value is corresponding to a original value of > 2000 mg/kg bw technical solution.

Executive summary:

In this GLP compliance study performed according to OECD guideline 402, 5 female and 5 male rats (Sprague-Dawley CD) were exposed to the test substance at a concentration of 2000 mg/kg body weight for 24 hours under semi-occlusive conditions. After this period the test substance was removed with cotton wool moistened with 3% Teepol followed by warm water, and the animals were observed for a period of 14 days. No mortality and clinical signs were observed. Animals showed expected weight gains during the study and no abnormalities were observed at autopsy. Some mild skin reactions were noted including Very slight to well-defined erythema and haemorrhage of dermal capillaries, crust formation, small superficial scattered scabs and glossy skin. The LD50 was determined to be >2000 mg/kg body weight for males, females and sexes combined, which corresponds to a recalculated value of 922 mg pure substance/kg bw.