Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP; does not fully conform to current guidelines-no individual responses

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1987

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Remarks:
pre-GLP; QA declaration
Test type:
standard acute method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
Redicote EN611, an amber liquid, was received on 26 February 1987 and stored at ambient temperature.
Redicote EN611 (before 2000 name changed to Redicote 611) contains 30-40% active substance, with 10-15% CaCl2 and 50-60% water (SDS).

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Equal numbers of male and female CFY (Sprague-Dawley origin) rats were obtained from Interfauna UK Ltd., Huntingdon, Cambridgeshire, England.
They were in a weight range of 89 to 121 g prior to dosing (Day 1) in the main study and approximately four to six weeks of age. All the rats were
acclimated to the experimental environment for a period of 5 days prior to the start of the main study.

The rats were allocated to cages within the treatment groups. They were housed in groups by sex in metal cages with wire mesh floors. A standard
laboratory rodent diet (Labsure LAD 1) and water were provided ad libitum. The batch of diet used for the study was analysed for certain chemical and
microbiological contaminants. Access to food only was prevented overnight prior to and approximately 4 hours after dosing.

The mean daily minimum and maximum temperatures of the animal room were 21°C and 22°C respectively and the mean daily relative humidity value
was 47%. The rate of air exchange was maintained at approximately 15 air changes/hour. Lighting was controlled by means of a time switch to 12
hours artificial light in each 24 hour period.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Redicote EN611 was administered, as supplied by the Sponsor, at a volume not exceeding 1.52 ml/kg (S.G. 1.05) in the main study.
Doses:
A trial test was carried out to establish a dosing regimen for the main study using groups of two male and two female rats at three dose levels of
1000, 2500 and 5000 mg/kg bodyweight.

Doses selected for the main study were 640, 1000 and 1600 mg/kg bodyweight.

No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
The appropriate dose volume of the test substance was administered to each rat using a syringe and plastic catheter.

Animals were observed soon after dosing; then at frequent intervals for the remainder of Day 1. On subsequent days the animals were observed once in the morning and again at the end of the experimental day. This latter observation was at approximately 16.30 hours on weekdays or 11.30 hours on Saturday and Sunday. Clinical signs were recorded at each observation.

The animals on the preliminary and main studies were observed for 5 and 14 days respectively, after dosing.

Surviving animals on the main study were killed on Day 15 by cervical dislocation. All animals that died during the study and those killed on Day 15
were subjected to a macroscopic post mortem examination which consisted of opening the abdominal and thoracic cavities. The macroscopic
appearance of abnormal organs when present was recorded.
Statistics:
The acute median lethal oral dose (LD50) to male and female rats was calculated using the method of: Finney (1971) Probit Analysis (3rd Edition)
Cambridge University Press. Separate LD 50 values for males and females were estimated by undertaking probit analysis on the mortality data by
fitting two parallel lines on the data (males only and females only) using the technique described by Finney 1978, Statistical Method in Biological
Assay, 3rd Edition, Charles Griffin, London). A chi-squared test was carried out to check that the data did not contain any evidence for
non-parallelism.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
1 145 mg/kg bw
95% CL:
871 - 1 543
Sex:
female
Dose descriptor:
LD50
Effect level:
1 164 mg/kg bw
95% CL:
893 - 1 506
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 156 mg/kg bw
95% CL:
956 - 1 405
Mortality:
There were deaths among male and female rats treated at 1000 (3/10) and 1600 mg/kg (9/10) from within one hour of dosing to Day 2.
Clinical signs:
Signs of reaction to treatment observed in all rats shortly after dosing were pilo-erection, abnormal body carriage (hunched posture),
abnormal gait (waddling) and increased salivation. These were accompanied by: lethargy and decreased respiration in all animals surviving
for more than one hour after treatment at 1000 or 1600 mg/kg, ptosis in one rat dosed at 640 mg/kg and in all rats surviving for more than one hour after treatment at higher doses, pallor of the extremities of one rat dosed at 640 mg/kg and in all animals given higher doses, diarrhoea in all rats
treated at 640 mg/kg. Recovery, as judged by external appearance and behaviour, was advanced by Day 3 and complete by Day 5.
Body weight:
Bodyweight losses or no change of bodyweight were recorded for rats that died.

Slightly low bodyweight gains were recorded on Day 8 for one male dosed at 1000 mg/kg and on Day 15 for one female treated at 640 mg/kg. Other
rats achieved anticipated bodyweight gains throughout the study.
Gross pathology:
Autopsy of rats that died commonly revealed renal pallor. There were no other macroscopic abnormalities.Terminal autopsy findings were normal.

Any other information on results incl. tables

Time and Number of Deaths

Sex

Dose

(mg/kg)

# deaths

Total #

animals

Day 1

Day 2

Day 3

Day 4

Day

5-15

a     b

a     b

a     b

a     b

a     b

M

640

0

5

M

1000

1

5

1

M

1600

5

5

5

F

640

0

5

F

1000

2

5

        2

F

1600

4

5

4

a = first, b = second observation

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The acute oral LD50 of Redicote EN611 and its 95% confidence limits were estimated to be 1156 mg/kg bodyweight (956-1405).
Executive summary:

The purpose of the study was to evaluate the acute toxicity of Redicote EN611 when administered to rats by gavage in accordance with OECD 401. Male and female rats were administered the test article at 640, 1000 or 1600 mg/kg bodyweight and observed for clinical signs of toxicity and mortality.

The combined LD50 of Redicote EN611 was 1156 mg/kg (956 -1405).

As Redicute EN611 contains 30-40% active substance, this equals 350-450 mg a.s./kg;