Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
December 1984 - January 1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant study conducted in accordance with international guidelines.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Principles of method if other than guideline:
Not applicable.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: yellowish-white liquid
Details on test material:
Label: P5306
Storage: In a cool place at less than 30°C

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Ten male and 10 female Wistar-derived rats of the Cr1:(WI)BR strain obtained from Charles River (UK) Ltd., Margate, were used for the study.
On the day before treatment the weight of the males was between 210 and 224 g, those of the females between 195 and 206 g. The animals were
acclimatised to the laboratory environment for at least 3 days. Before starting the study all animals were examined for signs of ill health or injury.
All animals appeared healthy and no animals were discarded. The animals were housed in a single air conditioned room maintained at a temperature
and relative humidity of 19 to 25°C and 40 to 70% respectively. Fluorescent lighting was automatically controlled to give a cycle of 12 hours light
and 12 hours darkness. Environmental conditions were recorded twice daily on week-days and once daily at week-ends.
Animals were housed in groups of 5 by sex in grid floor stainless steel cages. Water bottles were cleaned at intervals during the study.
With the exception of an overnight fast prior to dosing the animals were allowed free access to food (SQC Rat and Mouse Maintenance Diet No.1,
Expanded; Special Diets Services Ltd., Witham). Mains water was provided at all times and dispensed from glass water bottles. The diet and drinking
water were considered not to contain any contaminant at a level that might have affected the objectives or integrity of the study.
The food was re-introduced immediately after treatment.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Doses:
Screening study:
---------------
50, 250, 1000, 2000 and 5000 mg/kg

Single dose level study:
---------------------
5000 mg/kg
No. of animals per sex per dose:
Screening study:
---------------
50, 250, 1000, 2000 and 5000 mg/kg (five groups), each of 2 rats (1 male, 1 female)

Single dose level study:
---------------------
One group of 10 rats (5 males, 5 females)
Control animals:
no
Details on study design:
The test article preparations were administered once only by oral gavage using a metal stomach tube (14 gauge x 8 cm long,
Stand Medicals Ltd., Manchester) attached to a disposable plastic syringe. Fresh formulations of the test article were made for each
study.

Results and discussion

Preliminary study:
Not applicable.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortalities occurred in the screening study. In the single dose level Study all animals survived the study period.
Clinical signs:
All animals appeared normal throughout the study period.
Body weight:
All animals showed body weight gain at the end of the observation period.
Gross pathology:
All animals were subjected to necropsy. No abnormalities were noted.
Other findings:
No other findings were observed.

Any other information on results incl. tables

Single dose level study:

Appearance, behaviour and general observations:

All animals were observed for overt signs of toxicity or behavioural changes at 1/4, 1, 2 and 4 hours after treatment and subsequently once daily for 14 days. All observations were recorded.

Body weight:

Individual body weights were recorded on the day before treatment (day-1), on the day of treatment, and on days 7 and 14. Necropsy:

All animals were subjected to a gross necropsy examination. No tissues were retained. The animals were killed by exposure to high levels of carbon dioxide.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral median lethal dose (LD50) of P5306 in the Wistar-derived rat was estimated to be greater than 5000 mg/kg bodyweight.
Executive summary:

The acute oral toxicity study was performed from Dezember 1984 - January 1985 according to OECD Guideline 401 and GLP.

No mortalities occurred throughout the study period. No clinical signs were observed. All animals were subjected to necropsy. No abnormalities were noted. The acute oral median lethal dose (LD50) of P5306 in the Wistar-derived rat was estimated to be greater than 5000 mg/kg bodyweight.