estr-4-ene-3,11,17-trione cyclic 3-(1,2-ethanediylmercaptole)

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:

other: Study performed at a registered GLP site and reported a high standard andis in compliance with recognised OECD standards with no deviations.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

yes

Principles of method if other than guideline:

No analysis was carried out to determine the homogeneity, concentration or stability of the test item formulation. The test item was formulated within two hours of it being applied to the test system; it is assumed that the formulation was stable for this duration. This exception is considered not to affect the purpose or integrity of the study.

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Test material

Test material information

Constituent 1

Reference substance name:

11-KN

IUPAC Name:

11-KN

Constituent 2

Reference substance name:

estr-4-ene-3,11,17-trione cyclic 3-(1,2-ethanediylmercaptole)

Molecular formula:

C20H26O2S2

IUPAC Name:

estr-4-ene-3,11,17-trione cyclic 3-(1,2-ethanediylmercaptole)

Constituent 3

Reference substance name:

920-684-2

EC Number:

920-684-2

IUPAC Name:

920-684-2

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): 11-KN
- Physical state: White powder
- Lot/batch No.: CGG238K1
- Expiration date of the lot/batch: 12 February 2014
- Storage condition of test material: room temperature in the dark

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: supplied by Harlan Laboratories UK Ltd., axon, UK.
- Age at study initiation: At the start of the study the animals were eight to twelve weeks of age.
- Mean weight at study initiation: 165 g
- Fasting period before study: overnight fast immediately before dosing and for approximately three to four hours after dosing
- Housing: suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum):free access to food (2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., axon, UK)
- Water (e.g. ad libitum):free access to mains drinking water
- Acclimation period: acclimatization period of at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70%
- Air changes (per hr): fifteen changes per hour
- Photoperiod (hrs dark / hrs light): 12 dark / 12 light

IN-LIFE DATES: From: day 0 To: day 14

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 mg/ml 200 mg/ml
- Amount of vehicle (if gavage): dose volume was 10 mL/kg bw
- Justification for choice of vehicle: Arachis oil BP was used because the test item did not dissolve/suspend in distilled water.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

Doses:

300mg/kg bw
2000 mg/kg bw

No. of animals per sex per dose:

1 female @ 300 mg/kg bw
5 females @ 2000 mg/kg bw

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days (or other?)
- Frequency of observations and weighing: Clinical observations performed daily, Body weights measured on days 0, 7, 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic observations

Statistics:

The test item was classified according to Annex 3 of the OECD Guidelines for Testing of Chemicals No. 420 "Acute Oral Toxicity - Fixed Dose Method" (adopted 17 December 2001) .
Evaluation of data included identification of the number of animals that died during the study (or that were killed for humane reasons), and determination of the nature, severity, onset and duration of the toxic effects. If possible, the signs of evident toxicity were described. Evident toxicity refers to the toxic effects of sufficient severity that administration of the next higher dose level could result in development of severe signs of toxicity and probable mortality. Effects on
body weights and abnormalities noted at necropsy were also identified.
Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test item was made.

Results and discussion

Preliminary study:

At 300 mg/kg bw there was no mortality. No signs of systemic toxicity were noted during the observation period. The animal showed expected gains in body weight over the observation period. No abnormalities were noted at necropsy
Based on the results of this preliminary study at a dose level of 300 mg/kg, a dose level of 2000 mg/kg bodyweight was investigated.

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

No signs of systemic toxicity were noted during the observation period.

Body weight:

All animals showed expected gains in body weight over the observation period.

Gross pathology:

No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight (Globally Harmonized Classification System - Unclassified).

Executive summary:

The study was performed to assess the acute oral toxicity of the test item in the Wistar strain rat.

Following a sighting test at dose levels of 300 mg/kg and 2000 mg/kg, a further group of four fasted females was given a single oral dose of test item, as a suspension in arachis oil BP, at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality. There were no deaths.

Clinical Observations. There were no signs of systemic toxicity.

Body Weight. All animals showed expected gains in body weight.

Necropsy. No abnormalities were noted at necropsy.

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight (Globally Harmonized Classification System - Unclassified).