picoxystrobin (ISO); methyl (2E)-3-methoxy-2-[2-({[6-(trifluoromethyl)pyridin-2-yl]oxy}methyl)phenyl]acrylate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

up-and-down procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

methyl (E)-3-methoxy-2-{2-[6-(trifluoromethyl)pyridin-2-yloxymethyl]phenyl}acrylate

EC Number:

601-478-9

Cas Number:

117428-22-5

Molecular formula:

C18H16F3NO4

IUPAC Name:

methyl (E)-3-methoxy-2-{2-[6-(trifluoromethyl)pyridin-2-yloxymethyl]phenyl}acrylate

Test material form:

solid

Details on test material:

- Purity: 99.3%

Test animals

Species:

mouse

Strain:

CD-1

Remarks:

(CRL: CD1(ICR))

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Bred at IIBAT animal house facility
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 23-28 g
- Fasting period before study: 3 hours prior to dosing.
- Housing: Standard polypropylene mouse cages with stainless steel top grills
- Diet: ad libitum except during fasting
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20.1-23.0°C
- Humidity: 51-58%.
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

methylcellulose

Remarks:

0.5% aqueous methylcellulose

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg.b.w.

Doses:

1750 and 5000 mg/kg bw

No. of animals per sex per dose:

1750 mg/kg: 1
5000 mg/kg: 3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for clinical signs at half an hour, 1, 2, 3 and 4 hours after dosing, then once daily for 14 days. Body weight of each animal was recorded on day 0 (prior to dosing) and on day 7 and 14.
- Necropsy of survivors performed: yes

Statistics:

The LD50 was calculated by using the software AOT425 StatPgm

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No morbidity/mortality was observed in treated animals throughout the observation period.

Clinical signs:

other: Two mice dosed at 5000 mg/kg b.w. exhibited dullness at 30 minutes after the test substance administration and recovered by 1 hour. No clinical signs were observed in the remaining animals.

Gross pathology:

No macroscopic lesions were present in the animals at necropsy conducted at the end of the experimental period.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 (Female): >5000 mg/kg bw

Executive summary:

Acute oral toxicity of the test substance was tested in female CD1 mice. The study was conducted as per the OECD guideline (Guideline No. 425, Adopted 3rd October, 2008) and U.S. EPA Heath Effects Test Guidelines OPPTS 870.1100 (2002).

The test substance, mixed with 0.5% aqueous methylcellulose, was administered as a single oral gavage dose to one fasted female mouse at a dose level of 1750 mg/kg and to three fasted female mice at a dose level of 5000 mg/kg using a stainless steel ball tipped oral intubation needle. The animals were dosed in sequence at a minimum of 48 hour intervals.

Animals were observed for clinical signs of toxicity, morbidity/mortality for a 14 day observation period. Weekly body weights were recorded. At the end of the observation period, the animals were sacrificed for gross pathology observation.

No deaths occurred. Two of the mice dosed at 5000 mg/kg exhibited dullness at half an hour after dosing. No other clinical signs were observed. Weekly body weight gain was observed. Gross pathology examination revealed no lesions.

In conclusion, the acute oral LD50 of the test substance was determined to be greater than 5000 mg/kg bw.