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Administrative data

Description of key information

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).

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:
Experimental start date 16 October 2017 Experimental completion date 02 November 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes
Test material information:
Composition 1
Specific details on test material used for the study:
Identification:1,1-Dimethoxyethane (CAS no. 534-15-6)
CAS Number: 534-15-6
Batch: 1706291650R
Purity: 99.92%
Physical state/Appearance: clear colorless liquid
Expiry Date: 29 June 2019
Storage Conditions: room temperature in the dark
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
Animal Information
Female Wistar (RccHanTM :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 dosed animals at the start of treatment.

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 o 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.
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 as supplied. The specific gravity was determined and used to calculate the appropriate dose volume for the required dose level.
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 females at 2000 mg/kg
Control animals:
no
Details on study design:
Using available information on 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 was 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.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
One animal was humanely killed one hour after dosing as it was considered to have exceeded the severity limit set forth by the UK Home Office.
Clinical signs:
Signs of systemic toxicity noted during the day of dosing included hunched posture, prostration, decreased and labored respiration, dehydration, and coma.
Body weight:
All surviving animals showed expected gains in body weight over the observation period.
Gross pathology:
Abnormalities noted at the necropsy of the animal that was humanely killed during the study included a renal cavity in the left kidney and pale and thickened gastric mucosa. No abnormalities were noted at the necropsies of the animals that were killed at the end of the observation period.
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, as supplied, 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 humanely killed one hour after dosing as it was considered to have exceeded the severity limit set forth by the UK Home Office.

Clinical Observations. Signs of systemic toxicity noted during the day of dosing included hunched posture, prostration, decreased and labored respiration, dehydration, and coma.

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

Necropsy. Abnormalities noted at the necropsy of the animal that was humanely killed during the study included a renal cavity in the left kidney and pale and thickened gastric mucosa. No abnormalities were noted at the necropsies of the 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).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw

Additional information

Justification for classification or non-classification

The LD50 by oral and dermal administration to rats was determined to be greater than 2000 mg/kg; on this basis no classification is required for oral toxicity according to the CLP regulation.