Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11th October 2005 - 7th November 2005
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study performed to GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report Date:
2006

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
other: Annex (Acute toxic class)
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: Liquid

Test animals

Species:
other: Rat (Sprague-Dawley)
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
Source: Charles River (UK) Ltd
Environmental conditions:
Housed in groups of 3 in suspended solid floor cages furnished with wood flakes.
Temperature: 119-25ºC
Humidity: 30-70%
Acclimitisation period: 5 days
Air changes: 15 per hour
Lighting: 12 hours continuous light and twelve hours darkness

Access to mains drinking water and food (with the exception of an overnight fast immediatley before dosing and 3-4 hours after dosing)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
Arachis Oil was used for the 300 mg/kg test concentration. At 2000 mg/kg the test material was delivered undiluted.
Doses:
2000 mg/kg, 300 mg/kg
No. of animals per sex per dose:
3
Control animals:
not specified
Details on study design:
All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted bodyweight at the time of dosing.
Treatment of animals was sequential. Sufficient time was allowed between each group and each dose level to confirm the survival of the previously dosed animals.
The animals were observed for deaths or overt signs of toxicity 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for up to fourteen days.
Individual bodyweights were recorded prior to dosing and seven and fourteen days after treatment or at death.
At the end of the observation period the surviving animals were killed by cervical dislocation. All animals were subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities for examination of major organs. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
< 2 000 mg/kg bw
Mortality:
Female: 2000 mg/kg bw; Number of animals: 3; Number of deaths: 3
Female: 300 mg/kg bw; Number of animals: 3; Number of deaths: 0
Clinical signs:
Signs of toxicity related to dose levels: At 2000mg/kg: All 3 animals died within 2 hours after dosing. Clinical signs include; hunched posture, lethargy, ataxia, ptosis, decreased respiratory rate, laboured respiration, increased salivation, splayed gait, loss of righting reflex and hypothermia. At 300mg/kg There were no clinical signs of systemic toxicity
Body weight:
The surviving animals showed expected gains in bodyweight over the study period.
Gross pathology:
Effects on organs: At 2000mg/kg, necropsy showed animals had abnormally red lungs, dark liver and dark kidneys. At 300mg/kg, there were no abnormalities noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was approximatley 500 mg/kg bodyweight (GHS Category 4 >300-2000 mg/kg bodyweight)
Executive summary:

A GLP study was performed to assess the acute oral toxicity of Inhibitor AHM P500 following a single oral administration to the Sprague-Dawley CD rat. The method was designed to meet the requirements OECD guideline 423.

A group of three fasted females was treated with the test material at a dose level of 2000 mg/kg bodyweight. Based on the results from this dose level, further groups of fasted females were treated at a dose level of 300 mg/kg bodyweight. Dosing was performed sequentially.

The test material was administered orally undiluted for the 2000 mg/kg dose level and orally as a solution in arachis oil BP for the 300 mg/kg dose level. Clinical signs and bodyweight development were monitored during the study. All animals were subject to gross necropsy.

All animals treated at a dose level of 2000 mg/kg were found dead approximately two and half hours after dosing. There were no deaths noted in animals treated at a dose level of 300 mg/kg.

Signs of systemic toxicity noted in animals treated at a dose level of 2000 mg/kg were hunched posture, lethargy, ataxia, ptosis, decreased respiratory rate, laboured respiration, increased salivation, splayed gait, loss of righting reflex and hypothermia. There were no signs of systemic toxicity noted in animals treated at a dose level of 300 mg/kg.

The surviving animals showed expected bodyweight gain over the study period.

Abnormalities noted at necropsy of animals that died during the study were abnormally red lungs, dark liver and dark kidneys. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was approximately 500 mg/kg bodyweight (GHS Category 4 >300-2000 mg/kg bodyweight).