Fatty acids, C18-unsatd., dimers, oligomeric reaction products with 1-chloro-2,3-epoxypropane

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Experimental start date 16 October 2017. Experimental completion date 02 November 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

Due to a technician error, the Day 3 clinical observations for the additional four treated animals were not recorded. This deviation was considered to have not affected the integrity or validity of the study.

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

yes

Remarks:

Due to a technician error, the Day 3 clinical observations for the additional four treated animals were not recorded. This deviation was considered to have not affected the integrity or validity of the study.

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Fatty acids, C18-unsatd., dimers, oligomeric reaction products with 1-chloro-2,3-epoxypropane

EC Number:

500-215-4

EC Name:

Fatty acids, C18-unsatd., dimers, oligomeric reaction products with 1-chloro-2,3-epoxypropane

Cas Number:

68475-94-5

Molecular formula:

Not applicable for a UVCB substance please see remarks section below.

IUPAC Name:

Reaction products of Fatty acids, C18-unsatd., dimers and trimer with 1-chloro-2,3-epoxypropane

Test material form:

liquid

Details on test material:

Identification: Fatty acids, C18-unsatd., dimers, polymers with epichlorohydrin
Batch: 52611021
CAS Number: 68475-94-5
EC Number: 500-215-4
Purity: 95-100%
Physical state / Appearance: Clear yellow liquid
Expiry Date: 01 December 2018
Storage Conditions: Room temperature in the dark

Specific details on test material used for the study:

Identification: Fatty acids, C18-unsatd., dimers, polymers with epichlorohydrin
Batch: 52611021
CAS Number: 68475-94-5
EC Number: 500-215-4
Purity: 95-100%
Physical state / Appearance: Clear yellow liquid
Expiry Date: 01 December 2018
Storage Conditions: Room temperature in the dark

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Animal Information
Female Wistar (RccHan™:WIST) strain rats were supplied by Envigo RMS (UK) Limited, Oxon, UK. On receipt the animals were randomly allocated to cages. The females were nulliparous and non-pregnant. After an acclimatization period of at least 5 days the animals were selected at random and given a number unique within the study by indelible ink-marking on the tail and a number written on a cage card. At the start of the study the animals were 8 to 12 weeks of age. The body weight variation did not exceed ±20% of the mean body weight of any previously treated animals.

Animal Care and Husbandry
The animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes. With the exception of an overnight fast immediately before dosing and for approximately 3 to 4 hours after dosing, free access to mains drinking water and food (2014C Teklad Global Rodent diet supplied by Envigo RMS (UK) Limited, Oxon, UK) was allowed throughout the study. The diet, drinking water and bedding were routinely analyzed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.
The temperature and relative humidity were set to achieve limits of 19 to 25 °C and 30 to 70% respectively. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give 12 hours continuous light and 12 hours darkness.
The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Test Item Preparation and Analysis
For the purpose of the study the test item was used undiluted as supplied. The specific gravity was determined and used to calculate the appropriate dose volume for the required dose level.
Dose volume: 2.05 mg/kg

Doses:

Dose level: 2000 mg/kg
Dose volume: 2.05 mg/kg

No. of animals per sex per dose:

A total of five female animals were therefore treated at a dose level of 2000 mg/kg in the study.

Control animals:

no

Details on study design:

Study Design
Based on available data regarding the toxicity of the test item, 2000 mg/kg was chosen as the starting dose.
A single animal was treated at 2000 mg/kg.
In the absence of toxicity at a dose level of 2000 mg/kg, an additional group of animals were treated at 2000 mg/kg.
A total of five animals were therefore treated at a dose level of 2000 mg/kg in the study.
All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted body weight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each dose group to confirm the survival of the previously dosed animals.
Clinical observations were made 30 minutes, 1, 2, and 4 hours after dosing and then daily for up to 14 days. Morbidity and mortality checks were made twice daily, early and late during normal working days, and once daily at weekends and public holidays.
Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14 or at death.
At the end of the observation period the surviving animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

One animal was found dead one day after dosing.

Clinical signs:

other: Signs of systemic toxicity noted in three of the additional four treated animals were lethargy, hunched posture, pilo-erection and ataxia. The initial treated animal appeared normal throughout the observation period and surviving animals appeared normal f

Gross pathology:

Abnormalities noted at necropsy of the animal that was found dead during the study were hemorrhagic lungs, dark liver, dark spleen, dark kidneys and hemorrhagic gastric mucosa. No abnormalities were noted at the necropsy of the animals that were killed at the end of the study

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

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 − Category 5).

Executive summary:

Introduction

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

Methods

Following a sighting test at a dose level of 2000 mg/kg, an additional four fasted female animals were given a single oral dose of the undiluted test item 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.

Results

Mortality. One animal was found dead one day after dosing.

Clinical Observations. Signs of systemic toxicity noted in three of the additional four treated females were lethargy, hunched posture, pilo-erection and ataxia. The initial treated animal appeared normal throughout the observation period and surviving animals appeared normal four days after dosing.

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

Necropsy. Abnormalities noted at necropsy of the animal that was found dead during the study were hemorrhagic lungs, dark liver, dark spleen, dark kidneys and hemorrhagic gastric mucosa. No abnormalities were noted at the necropsy of animals that were killed at the end of the study.

Conclusion

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 − Category 5).