Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
august 1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study was performed as a dose ranging study and a main study, and LC50 was calculated according to OECD guideline 401, however purity of test substance is not presented

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1977

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not applicable
Remarks:
Study was performed before guideline was accepted
Principles of method if other than guideline:
Initial dose-range finding study; Four groups of four fasted rats (2 males and 2 females) were dosed 0.5, 1.0, 2.0 and 4.0 g/kg bw, and death were recorded at daily intervals for seven days.
Main study; Four groups each of 10 fasted animals (5 males and 5 females) were dosed 0.26, 0.37, 0.52 and 0.73 g/kg bw, and death were recorded at daily intervals for forteen days
GLP compliance:
no
Remarks:
The study was performed before CLP regulation was implemented
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: Granular solid
Specific details on test material used for the study:
White granular solid, administered as a 10% w/v solution

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Animals were obtained from Charles River UK Ltd. Margate, Kent, and conditioned at least 3 days prior to the experiments. Body weigths were between 190 and 270 grams.
With the exeption of the overnight fast, 18-20 hours before treatment, the animals were allowed free access to filtered tapwater and food, rat and mouse No.1 expanded diet from B.P. Nutrition U.K. Ltd., Witham, Essex.
All animals were housed in a single air-conditioned room, at 22+/- 3 degrees celcius, and relative humidity 50% +/- 10%, exposed to natural light conditions.
Animals were caged in groups of two by sex in rangefinding study and five by sex in main study in polypropylene boxes with softwood sawdust,
sawdust was replaced twice weekly

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
The substance was given as 10% solution in water, by oral gavage with a metal stomach tube
Doses:
Initial dose-range finding study; Four groups of four fasted rats (2 males and 2 females) were dosed 0.5, 1.0, 2.0 and 4.0 g/kg bw
Main study; Four groups each of 10 fasted animals (5 males and 5 females) were dosed 0.26, 0.37, 0.52 and 0.73 g/kg bw
No. of animals per sex per dose:
Initial dose-range finding study; Four groups of four fasted rats (2 males and 2 females)
Main study; Four groups each of 10 fasted animals (5 males and 5 females)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observation at 1/4, 1/2, 1 and 2 hours after treatment, and subsequently once daily
- Necropsy of survivors performed: yes, one female and one male survivor from the lowest dose and the one female survivor from the highest dose
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Clinical signs, Body weigth, macroscopic anomalities
Statistics:
The acute LD50 was calculated by Finneys Probit Method to 0.39 g/kg bw, 95% confidence limit was 0.33-0.46 g/kg bw.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
0.39 other: g/kg
Based on:
test mat.
95% CL:
> 0.33 - < 0.46
Mortality:
Mortality in dose range finding study; Males; 50%, 100%,100% and 100%, for 0.5,1.0,2.0 and 4.0 g/kg bw, respectively
Mortality in dose range finding study; Females; 50%, 100%,100% and 100%, for 0.5,1.0,2.0 and 4.0 g/kg bw, respectively
Mortality in main study; Of the observed 24 deaths, 18 were observed between 24 and 48 hours. Mortality observed was 10%,40% 100% and 90%, for 0.26, 0.37, 0.52 and 0.73 g/kg bw, respectively.
Clinical signs:
All animals except in the lowest dose, 0.26 g/kg bw were subdued and lethargic within 15 min of treatment, this behaviour, together with hunched posture was still apparent up to 7 days later. Rats treated with 0.73 g/kg bw also showed piloerection and laboured respiration, between 24 and 72 hours after treatment
Body weight:
Surviving animals showed normal weight gain, with the exception of one female dosed with 0.37 g/kg bw, which showed decrease in bodyweight during the first 7 days, and subsequent increase during second week.
All females dosed with 0.26 g/kg bw showed reduced weight gain
Gross pathology:
One female and one male survivor, from the lowest dose and the one female survivor dosed with 0.73 g/kg bw, showed no macroscopic abnormalities

Applicant's summary and conclusion

Interpretation of results:
toxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral LD50 value was calculated to 0.39 g/kg bw, for rats. The 96% confidence limit was 0.33-0.46 g/kg bw.
Executive summary:

A study on the acute toxicity of tetradonium bromide on rats, was performed. A dose ranging study indicated a LD50 of approximately 0.5 g/kg bw, and the selected dosing for the main study was therefore 0.26, 0.37, 0.52 and 0.73 g/kg bw, respectively. 10 rats (five males and five females) were exposed to each dose, by oral gavage, and observed after 15, 30, 60 minutes, and 2 and 4 hours after treatment, and subsequently once daily. 18 of the observed 24 death occured between 24 and 48 hours. The LD50 was calculated by Finneys Probit Method to 0.39 g/kg bw, with the 95% confidence limit of 0.33 -0.46 g/kg bw.