Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
28th September 2004
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted in accordance with generally accepted scientific principles, possibly with incomplete or methodological deficiencies, which do not affect the quality of relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report date:
2004

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
other: Gaitonde Committee Guidelines Annexure III following method of Litchfield & Wilcoxon (1949)
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
2-hydroxy-3-[(3-{[3-(4-methoxyphenyl)prop-2-enoyl]amino}propyl)(dimethyl)ammonio]propane-1-sulfonate
EC Number:
695-243-8
Cas Number:
500731-87-3
Molecular formula:
C18H28N2O6S
IUPAC Name:
2-hydroxy-3-[(3-{[3-(4-methoxyphenyl)prop-2-enoyl]amino}propyl)(dimethyl)ammonio]propane-1-sulfonate
Test material form:
other: Liquid
Details on test material:
Characteristics of test substance:

Test substance: Galaxy Sunbeat (S-382)
Physical State: Liquid
Colour: Colourless
Quantity Recd: 25 g
Date of receipt of sample: 08/09/2004
Batch Number: S-382

Test animals

Species:
other: albino mice
Strain:
Swiss
Sex:
male/female
Details on test animals or test system and environmental conditions:
Test Animals:

Species: Albino mice
Strain: Swiss
Source: National Toxicology Centre
Weight Range: 20 to 24g
Age: 6 to 8 weeks
Sex: Male and female
Number: 5 male and 5 female
Housing: 5 of similar sex per cage
Diet: Pelleted food supplied by Nav Maharashtra Chakan Oil Mills Ltd., Pune
Water: Community tap water ad libitum
Room temperature: 20 to 24 degrees Celsius
Relative humidity: 40 to 60%
Light cycle: 12 hours light and 12 hours dark
Vehicle used: water
Dose volume: 1 ml/100 g

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
Ten mice, five male and five female, were assigned to the dose groups. The test substance was administered once by gavage to mice. The mice were deprived of feed 3 to 4 hours before the administration of the test substance. Water was allowed ad libitum. At the end of the observation period the surviving experimental animals were sacrificed, gross necropsy performed and all the animals carefully examined.

VEHICLE: water
DOSE VOLUME : 1 ml/ 100 g

Preliminary range finding study conducted:
Two mice per sex per dose were assigned to treatment as follows:

Group No. No. of mice/sex Doses (ml/kg)
1 2 5.000
2 2 2.500
3 2 1.250
4 2 0.625

The mice were observed for toxic symptoms and mortality for 7 days after dosing.

LD50 in mice:
From the data obtained in the preliminary range find study, 10 mice (5 male and 5 female) were assigned to the treatment as follows:

Group No. No. of mice/sex Dose (ml/kg)
M F
1 5 5.000

The mice were observed for toxic symptoms and mortality for 14 days after dosing.

Doses:
Preliminary range finding study conducted:
Dose range 0.625-5.0 ml/kg

Actual Dose study: 5.0 ml/kg (5000 mg/kg bw)

No. of animals per sex per dose:
Preliminary range finding study conducted with two mice per sex per dose assigned to treatment.

LD50 in mice:
From the data obtained in the preliminary range find study, 10 mice (5 male and 5 female) were assigned to the treatment.



Control animals:
no
Details on study design:
Observations:

Clinical observations:
Toxic symptoms and mortality were recorded at 1/2, 1, 2, 3, 4 and 24 hours and later twice a day thereafter upto 14 days to determine their general health, behaviour and moribund condition. Any abnormality observed during this period was recorded and the subsequent progress monitored.

Body weight: Animals were weighed individually on the day and on the day test substance was administered, weekly therefater and prior to sacrifice.

Necropsy: A gross necropsy was performed on all animals that died during the course of the test and sacrificed at the termination of the test.
Statistics:
No statistics reported.

Results and discussion

Preliminary study:
Group No. Doses (ml/kg) No. of animals died No. of animals treated
1 5.000 0/4
2 2.500 0/4
3 1.250 0/4
4 0.625 0/4
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no CL reported
Mortality:
LD50 in mice
Mortality Data

Group No. Doses (ml/kg) Hours Days No. died/No. treated
½ 1 2 3 4 1 2 3 4 5 6 7 8 9 10 11 12 13 14
1 5.000 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 NIL/10


Group No. Doses (ml/kg) No. of animals died/No. of animals treated Mortality
1 5.000 0/10 0%

LD50 with fiducial limits: In males and females >5.000 ml/kg
Clinical signs:
Clinical signs of intoxication:

Group 1 5.000 ml/kg: The test material caused no mortality.
Urination was seen in 2 males and 1 female at 4 hours after dosing. All the animals appeared normal and showed no clinical signs of intoxication from day 1 till the end of the study.
Body weight:
Body Weight Changes:

The percentage show body weight change compared with body weights at the start of the study (day 0)

Group Sex Group mean % weight change (days)
0 7 14
1 M 22.6 30.37 40.28
F 22.4 28.89 39.16
Gross pathology:
Necropsy finding:

Group Dose (ml/kg) Animals found dead Killed at termination
1 5.000 NIL NAD

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 value of "Galaxy-Sunbeat (S-382)" according to the Gaitonde Commitee Guidelines, in albino mice by the oral route, following the methods of Litchfield and Wilcoxon (1949) was found to be greater than 5.0 ml/kg (5000 mg/kg bw).

Executive summary:

The objective of the study was to determine the acute oral toxicity of "Galaxy-Sunbeat (S-382)" to albino mice following the Gaitonde Committee protocol.

The test material was administered by gavage to five mice per sex at the limit test. The mice were observed for 14 days after treatment.

Group 1 (5.000 ml/kg ): The test material caused no mortality. Urination was seen in 2 males and 1 female at four hours after dosing. All the animals appeared normal and showed no clinical signs of intoxication from day 1 till the end of the study.

The LD50 value of "Galaxy-Sunbeat (S-382)" in mice by the oral route was found to be greater than 5.000 ml/kg.