Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Experimental start date: 14 June 2017. Experimental completion date 10 July 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Reliability 1 is assigned because the study conducted according to OECD TG xxx in compliance with GLP, without deviations that influence the quality of the results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report Date:
2017

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
Identification: Lyrame
Physical state/Appearance: yellow viscous liquid
Storage Conditions: approximately 4 °C in the dark under nitrogen

Test animals

Species:
rat
Strain:
other: Female Wistar (RccHan™:WIST)
Sex:
female
Details on test animals 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 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 °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:
DMSO
Details on oral exposure:
For the purpose of the study the test item was freshly prepared, as required, as a solution in dimethyl sulfoxide. Dimethyl sulfoxide was used because the test item did not dissolve/suspend in distilled water or arachis oil BP.
The test item was formulated within 2 hours of being applied to the test system. It is assumed that the formulation was stable for this duration.
Doses:
2000 mg/kg
No. of animals per sex per dose:
1 female at 2000 mg/kg followed by 4 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.

In the absence of toxicity at a dose level of 2000 mg/kg, an additional group of animals 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 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.
At the end of the observation period the 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
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 in the initial treated animal during the observation period.
Hunched posture and ataxia were noted in the four additional treated animals during the day of dosing. These four animals appeared normal 1 day after dosing
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:
other: not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The acute oral toxicity test showed an LD50 as >2000 mg/kg bw and is therefore not classified according to CLP criteria
Executive summary:

Lyrame was tested according to OECD Guideline for Testing of Chemicals No 420 "Acute Oral Toxicity - Fixed Dose Procedure" (2001)

Acute oral toxicity: In this study, 5 rats (0 males and 5 females) were administered the substance at dose levels of 2000 mg/kg bw. The rats showed no mortality, clinical signs, or treatment related effects at necropsy. All animals showed expected increases in bodyweight over the observatopn period. The acute oral LD50 for the substance in female rats was determined to be > 2000 mg/kg bw.