Registration Dossier

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:
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:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: TOXI COOP ZRT.
- Females (if applicable) nulliparous and non-pregnant: [yes/no] yes
- Age at study initiation: 8-9 weeks
- Weight at study initiation: 190-194 g
- Housing: group caging (3 animals/cage)
- Diet (e.g. ad libitum): ssniff SM R/M-Z+H complete diet for rats, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 12 and 13 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-3
- Humidity (%): 30-70%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12-12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
methylcellulose
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/ml
- Amount of vehicle (if gavage): 10 ml/kg bw.


MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg bodyweight

Doses:
2000 mg/kg
No. of animals per sex per dose:
2*3 females (2000 mg/kg)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observed individually after dosing at least once during the first 30 minutes, then 1 h, 2 h, 3 h, 4 h after the treatment and twice each day for 14 days thereafter; the body weights were recorded on day 0, on day 7 and on day 15
- Necropsy of survivors performed: yes on Day 15

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No death occurred at 2000 mg/kg bw single oral dose of 3,4-O-dimehyl methyldopa monohydrochloride monohydrate (DMAKS). All female rats in step 1 and step 2 survived until the end of the 14-day observation period.
Clinical signs:
In group 1 and 2 treated with 2000 mg/kg bw dose no treatment related symptoms were observed throughout the 14-day post treatment
Body weight:
The mean body weight of animals treated with 2000 mg/kg bw dose corresponded to their species and age throughout the study.
Gross pathology:
All animals treated with 2000 mg/kg bw dse survived until the scheduled necropsy on Day 15. Severe hydrometra was observed in female No.: 6207 of the group 1 nad moderate hydrometra was detected in animal No.: 6229 of group 2. Hydrometra os physiological finding and connected to the cycle of the animal. No pathological changes were found related to the effect of the test item during the macroscopic examination of animals treated with 2000 mg/kg bw dose.

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
The method used is not intended to allow the calcuation of a precise LD50 value. The test item is ranked into classes of Globally Harmonized Classification System (GHS) described in the OECD Guideline No. 423. as unclassified.