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Diss Factsheets

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:
2001
Report date:
2001

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
2-methoxy-N,N,β-trimethyl-10H-phenothiazine-10-propylamine
EC Number:
212-706-8
EC Name:
2-methoxy-N,N,β-trimethyl-10H-phenothiazine-10-propylamine
Cas Number:
851-68-3
Molecular formula:
C19H24N2OS
IUPAC Name:
2-methoxy-N,N,β-trimethyl-10H-phenothiazine-10-propylamine
Test material form:
solid: crystalline

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: TOXI-COOP Ltd. (Budapest, H1103, Cserkesz street 90.)
- Age at study initiation: 7 weeks
- Fasting period before study: overnight (after the test item administration food was withheld for 3 hours)
- Housing: 3 animals / cage in MAKROLON II type cages. (37x29x19 cm)
Cages with bedding were steam-sterilized at 121 °C for 20 minutes.
- Bedding: LIGNOCEL type (steam-sterilized) pure soft woodcut
- Diet (e.g. ad libitum): ad libitum, CRLT / N standard diet for rodent (Szinbád Kft.)
- Water (e.g. ad libitum): ad libitum, potable water, offered daily in MAKROLON type drinking bottles sterilized before use
- Acclimation period: 6 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.6 -24.3 °C
- Humidity (%): 37.6-68.7 %
- Air changes (per hr): 10-15 / h
- Photoperiod (hrs dark / hrs light): 12 h dark / 12 h artificial light

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 1 % aqueous methylcellulose
Details on oral exposure:
VEHICLE 1% aqueous methylcellulose
- Concentration in vehicle: 2000 mg / 20 ml suspension and 200 mg / 20 ml suspension
- Amount of vehicle (if gavage): 20 ml / kg bw.

MAXIMUM DOSE VOLUME APPLIED: 2000 mg / kg bodyweight
Doses:
2000 mg / kg in female rats (n=3)
200 mg / kg in male and female rats (n=3-3)
No. of animals per sex per dose:
3 females and 3 males (200 mg/kg)
3 females (2000 mg/kg)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations : for 6 hours after treatment and then twice a day
and weighing just before treatment, after 24 hours, on the 8th and 14th day
- Necropsy of survivors performed: yes (macroscopic)
- Other examinations performed: individual observations included the status of skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic, central nervous system and somatomotor activity as well

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
approximate LD50
Effect level:
> 200 - 2 000 mg/kg bw
Mortality:
Three females died (3/3) after 2000 mg/kg dose of the test item.
Clinical signs:
Serious CNS depressive symptoms (somnolence and dyspnea in 10 minutes) occured in the 2000 mg/kg female dose group. All of the animals died inthis dose group in the first 48 hours. Animals in the 200 mg/kg dose groups show somnolence after treatment. One day after treatment with 200 mg/kg test item animals became symptom-free.
Body weight:
The mean body weights decreased in the 200 mg/kg dose groups on the 2nd day of the study. After this the mean body weights and body weight gain changed in a similar manner in the 200 mg/kg dose groups that expected from control animals of the same age and strain in both sexes.
Gross pathology:
In the females, died on study, gross pathology revealed acute circulatory inefficiency and gastrointestinal disturbances (mottled lungs with haemorrhages, stomach and intestines filled with gaseous fluidy content, congestioned mucosa of gastrointestinal tract) as the cause of death. No pathological macroscopic findings could be detected at terminal sacrifice.

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions the approximate calculated LD50 value of the RACEM TISERCIN BASE, administered by oral route to Wistar rats was between 200 and 2000 mg/kg so according to the requirements of the Minister of Health 44/2000(XII.27) EÜM regulation the test item was classified to LD50:> 200-2000 mg/kg Xn Harmful category.