Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
July 2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report Date:
2004

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Borchen, Germany
- Strain: Hsd Cpb:WU (SPF)
- Age at study initiation: 10-14 weeks
- Mean weight at study initiation: 166-205 g
- Housing: in groups of 3 animals
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 55 +/- 5
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: formulated in demineralized water with the aid of 2% Cremophor EL
Details on oral exposure:
- Application volume: 10 mL/kg bw

- Rationale for the selection of the starting dose:
As described in the flow charts of Annex 2, OECD guideline 423, the starting dose level should be that which is most likely to produce mortality in
some of the dosed animals. Therefore, the limit dose 2000 mg/kg bw was chosen as starting dose.
Doses:
300 and 2000 mg/kg
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: at least once daily (clinical signs, mortality) or once weekly (weight gain)
- Necropsy of survivors performed: yes
Statistics:
none (limit test)

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
other: LD50 cut-off
Effect level:
2 000 mg/kg bw
Based on:
test mat.
Mortality:
At the dose 2000 mg/kg bw 4 out of 6 animals died within 2 days after treatment. The dose 300 mg/kg bw was tolerated by all 6 females without mortalities.
Clinical signs:
At 2000 mg/kg bw decreased motility, uncoordinated gait, narrowed palpebral fissure, lateral position, spasmodic state, tachypnea, abdominal position, labored breathing, temporary lateral position, poor reflexes, lacrimation/increased lacrimation and dyspnea were observed up to day 2 after treatment. The dose 300 mg/kg bw was tolerated by all animals without clinical signs.
Body weight:
Body weight development was not affected.
Gross pathology:
No gross pathological findings were observed in animals that died during the observation period and at the end of the study.
Other findings:
none

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information
Executive summary:

According to OECD TG 423 the LD50 cut-off of Picolinamid-Phenylether is 2000 mg/kg bw (Category 4 of the Globally Harmonized Classification System). At the limit-dose 2000 mg/kg bw 4 out of 6 animals died within 2 days after treatment. The dose 300 mg/kg bw was tolerated by all 6 females without mortalities. At 2000 mg/kg bw decreased motility, uncoordinated gait, narrowed palpebral fissure, lateral position, spasmodic state, tachypnea, abdominal position, labored breathing, temporary lateral position, poor reflexes, lacrimation/increased lacrimation and dyspnea were observed up to day 2 after treatment. The dose 300 mg/kg bw was tolerated by all animals without clinical signs. In both doses neither effects on body weight gain nor gross pathological findings were observed.