2-[4,5-dihydro-4-methyl-4-(1-methylethyl)-5-oxo-1H-imidazol-2-yl]-3-pyridine carboxylate; imazapyr (ISO)

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2013-02-04 to 2013-02-26

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

February 1987

Deviations:

no

Test guideline 2

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:

Bioassay Labor für biologische Analytik GmbH, Im Neuenheimer Feld 515/519, 69120 Heidelberg, Germany

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Test material form:

solid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Lot/batch No.of test material: COD-001701
- Expiration date of the lot/batch: 2014-11-01
- Purity test date: 2012-11-13

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature (or cooler)

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: males: 8 weeks, females: 12 weeks
- Weight at study initiation: males: 226 g to 239 g, females: 206 g to 218 g
- Housing: single housing, Makrolon cage, type III
- Diet: VRF1(P); (SDS Special Diets Services, 67122 Altrip, Germany) (ad libitum)
- Water: Tap water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 to 70 relative humidity
- Air changes (per hr): approx. 20
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To: 2013-02-04 to 2013-02-19

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

0.5% solution

Details on dermal exposure:

TEST SITE
- Area of exposure: 40 cm2
- % coverage: 10

- Type of wrap if used: The test item was covered with an air-permeable dressing (4 layers of absorbent gauze)

REMOVAL OF TEST SUBSTANCE
- Washing: rinsing with warm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount applied: 5000 mg/kg bw
- Concentration: 60 g/100 mL
- Constant concentration used: yes
- For solids, paste formed: no (suspension)

VEHICLE
- Amount(s) applied: 8.33 mL/kg bw (Administration volume)
- Concentration: 60 g/100 mL
- Purity: 0.5% solution of CMC in deionised water

Duration of exposure:

24 h

Doses:

5000 mg/kg bodyweight

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: Recording of clinical signs several times on the day of administration, and at least once daily thereafter each workday for the individual animals.
- Frequency of weighing: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, mortality

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

No systemic clinical signs were observed during clinical examination.

Body weight:

The mean body weight of the male animals increased within the normal range throughout the study period. The mean body weight of the female animals only slightly increased during the first post-exposure observation week, probably due to the bandage procedure, but increased during the second week within the normal range.

Gross pathology:

No macroscopic pathologic abnormalities were noted in the animals (5 males and 5 females) examined on the last day of observation.

Other findings:

No local effects were observed.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met