Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 2017-04-11 to 2017-05-04
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
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
10-Methoxy-9,10-dihydrolysergic methylester
Cas Number:
23495-64-9
Molecular formula:
C18 H22 N2 O3
IUPAC Name:
10-Methoxy-9,10-dihydrolysergic methylester
Specific details on test material used for the study:
Batch No.: 16023LS4B5
Purity: 98.3%

Test animals

Species:
rat
Strain:
other: Crl: WI(Han)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: Young adult animals (approximately 8-11 weeks old) were selected
- Weight at study initiation: 162 to 196 g
- Housing: On arrival and following assignment to the study, animals were group housed (up to 5 animals of the same sex and same dosing group together) in polycarbonate cages containing sterilized sawdust as bedding material equipped with water bottles.
- Diet: ad libitum pelleted rodent diet
- Water: Municipal tap-water was freely available to each animal via water bottles.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18°C to 24°C (Target), 21 °C (Actual)
- Humidity (%): 40% to 70% (Target), 43 to 49% (Actual)
- Air changes (per hr): Ten or greater
- Photoperiod (hrs dark / hrs light): A 12-hour light/12-hour dark cycle

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Polyethylene glycol 400
Details on oral exposure:
VEHICLE
- Amount of vehicle: 10 mL/kg body weight
- Justification for choice of vehicle: Trial preparations were performed at the Test Facility to select the suitable vehicle and to establish a suitable formulation procedure.


DOSAGE PREPARATION (if unusual):

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The dose levels were based on the OECD test guidelines and were selected from the series 5 (lowest dose level), 50, 300 and 2000 (highest dose level) mg/kg body weight. The starting dose level should be the one that is likely to produce mortality in at least some of the animals and was selected based on available toxicity data of the test item.
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
Each dose group consisted of 3 animals.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:general health/mortality and moribundity: twice daily. Body Weights: on Day 1 (predose), 8 and 15. Clinical observation: postdose observations were performed at periodic intervals on the day of dosing (at least three times) and once daily thereafter.

- Necropsy of survivors performed: yes, at the end of observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Hunched posture, piloerection and/or salivation were noted for all animals on Day 1.
Body weight:
The body weight gain shown by the animals over the study period was considered to be normal.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 value of test item in Wistar rats was established to exceed 2000 mg/kg body weight.
Executive summary:

The study was carried out in compliance with the guideline OECD No.423 (2001) "Acute Oral Toxicity, Acute Toxic Class Method".

The test substance was administered by oral gavage to two consecutive groups of three female Wistar rats at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body. Macroscopicexamination was performed after terminal sacrifice (Day 15).  

The oral LD50 value of test item in Wistar rats was established to exceed 2000 mg/kg body weight. According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.