Registration Dossier

Administrative data

Description of key information

Picolinamid-Phenylether is harmful after single oral exposure (LD50 cut-off, rat: 2000 mg/kg bw).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
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
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
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
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)
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
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.

 

 

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Quality of whole database:
The study is GLP compliant and is of high quality (Klimisch score=1)

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

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 (Schüngel, 2004).


Justification for selection of acute toxicity – oral endpoint
Only one study available

Justification for classification or non-classification

Based on the study results (oral LD50 cut-off value: 2000 mg/kg bw ) a classification with R22 (harmful if swallowed) according to Directive 67/548/EEC or with Acute Toxicity Cat. 4 (H302:harmful if swallowed) according to Regulation (EC) No. 1272/2008 (CLP) is required.