imiprothrin (ISO); reaction mass of [2,5-dioxo-3-(prop-2-yn-1-yl)imidazolidin-1-yl]methyl (1R,3S)-2,2-dimethyl-3-(2-methylprop-1-en-1-yl)cyclopropanecarboxylate and [2,5-dioxo-3-(prop-2-yn-1-yl)imidazolidin-1-yl]methyl (1R,3R)-2,2-dimethyl-3-(2-methylprop-1-en-1-yl)cyclopropanecarboxylate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

January 4 - February 21, 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test type:

up-and-down procedure

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

428-790-6

EC Name:

-

Cas Number:

72963-72-5

Molecular formula:

C17H22N2O4

IUPAC Name:

[2,5-dioxo-3-(prop-2-yn-1-yl)imidazolidin-1-yl]methyl (1R,3R)-2,2-dimethyl-3-(2-methylprop-1-en-1-yl)cyclopropane-1-carboxylate; [2,5-dioxo-3-(prop-2-yn-1-yl)imidazolidin-1-yl]methyl (1R,3S)-2,2-dimethyl-3-(2-methylprop-1-en-1-yl)cyclopropane-1-carboxylate

Test material form:

liquid: viscous

Details on test material:

Name: Imiprothrin
Appearance: viscous liquid
Colour: amber

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

Number of Animals: 9
Sex: Female, nulliparous and non-pregnant.
Age/Body Weight: Young adult (9-12 weeks)/193-208 grams at experimental start.
Animal Room Temperature and Relative Humidity Ranges: 19-23ºC and 39-60%, respectively.
Animal Room Air Changes/Hour: 13. Airflow measurements are evaluated regularly and the records are kept on file at Product Safety Labs.
Photoperiod: 12-hour light/dark cycle
Acclimation Period: 13-28 days
Food: ad libitum, except during fasting.
Water: Filtered tap water was supplied ad libitum.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Doses:

Based on a limit dose of 5000 mg/kg, a Main Test was conducted using a default starting dose level of 175 mg/kg which was administered to one healthy female rat by oral gavage. Following the Up and Down procedure, eight additional animals were dosed at levels of 175, 550, 1750, or 5000 mg/kg.

Details on study design:

The animals were observed for mortality, signs of gross toxicity, and behavioral changes approximately 30 minutes post-dosing, during the first several hours post-dosing and at least once daily thereafter for 14 days after dosing or until death occurred. Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea, and coma.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

1 750 mg/kg bw

Based on:

test mat.

95% CL:

> 651.9 - < 2 690

Mortality:

1750 mg/kg Dose Level (4 animals): three animals died within six hours of test substance administration. Prior to death, the animals exhibited irregular respiration and tremors.
5000 mg/kg Dose Level (1 animal): the animal died within two hours of test substance administration. Prior to death, the animal exhibited irregular respiration and tremors.

Gross pathology:

175 mg/kg Dose Level (1 animal): No gross abnormalities were noted for the animal when necropsied at the conclusion of the 14-day observation period.
550 mg/kg Dose Level (3 animals): No gross abnormalities were noted for these animals when necropsied at the conclusion of the 14-day observation period.
1750 mg/kg Dose Level (4 animals): Gross necropsy of the decedents revealed distention of the stomach and/or intestines and a liquid filled stomach. No gross abnormalities were noted for the surviving animal when necropsied at the conclusion of the 14-day observation period.
5000 mg/kg Dose Level (1 animal): Gross necropsy of the decedent revealed a liquid filled and distended stomach and distended intestines.

Other findings:

175 mg/kg Dose Level (1 animal): the animal survived exposure to the test substance, gained body weight, and appeared active and healthy during the study. There were no signs of gross toxicity, adverse clinical effects, or abnormal behavior.
550 mg/kg Dose Level (3 animals): all animals survived exposure to the test substance and gained body weight during the study. Following administration, one animal exhibited irregular respiration, reduced fecal volume and hypothermia. However, the animal recovered by Day 2 and along with the remaining two animals appeared active and healthy for the remainder of the 14-day observation period.
1750 mg/kg Dose Level (4 animals): following administration, the surviving animal was hypoactive and exhibited irregular respiration and reduced fecal volume. However, the surviving animal recovered by Day 2 and appeared active and healthy for the remainder of the 14-day observation period, gaining body weight over the course of the study.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Under the conditions of this study, the acute oral LD50 of the test substance is estimated to be 1750 mg/kg of body weight (based on the one dose with a partial response and an assumed sigma of 0.5) in female rats with a 95% PL 1confidence interval of 651.9 mg/kg (lower) to 2690 mg/kg (upper).