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Description of key information

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
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
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
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)
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.
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.
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).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
500 mg/kg bw

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1st November - 15th November 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study performed to GLP
Qualifier:
according to
Guideline:
other: Annex V
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Source: Charles River (UK) Ltd
Environmental conditions:
Housed individually during the 24 hour exposure period and then in groups of 5 by sex in suspended solid floor cages furnished with wood flakes for the remainder of the study.
Temperature: 19-25ºC
Humidity: 30-70%
Acclimitisation period: 5 days
Air changes: 15 per hour
Lighting: 12 hours continuous light and twelve hours darkness
Free access to mains drinking water and food throughout the study
Type of coverage:
semiocclusive
Vehicle:
other: None
Details on dermal exposure:
On the day before treatment the back and flanks of each animal were clipped free of hair.
Duration of exposure:
24 h
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 male, 5 female
Control animals:
not specified
Details on study design:
The calculated volume of test material was applied as evenly as possible to an area of shorn skin (approximatley 10% of the total body surface area) using a graduated syringe. A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage. The animals were caged individually for the 24-hour exposure period. After 24 hours the bandage was careully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test material. The animals were observed for overt signs of toxicity 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Clinical signs:
Signs of toxicity related to dose levels:
None
Body weight:
All animals showed expected bodyweight gain over the study period.
Gross pathology:
Effects on organs:
All animals were killed after 14 days observation. There
were no abnormalities noted at necropsy.
Other findings:
Signs of toxicity (local):
None
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight.
Executive summary:

A GLP study was performed in accordance with OECD method 402 in order to assess the acute dermal toxicity of Inhibitor AHM P500 to the Sprague-Dawley CD strain rat.

A group of ten animals (5 males, 5 females) was given a single, 24 hour semi-occluded dermal application of the undiluted test material to intact skin at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subject to gross necropsy.

No deaths or signs of systemic toxicity were observed during the course of the study. There were no signs of dermal irritation and all animals showed expected bodyweight gain over the study period.No abnormalities were noted at necropsy

The acute dermal median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw

Additional information

Guideline GLP studies are available for both oral and dermal toxicity and were considered acceptable for the purposes of classification and risk assessment.


Justification for selection of acute toxicity – oral endpoint
One GLP guideline study available.

Justification for selection of acute toxicity – dermal endpoint
One GLP guideline study available.

Justification for classification or non-classification

Based upon the above information the substance meets the criteria for classification as set out by both 67/548/EEC and EC Regulation 1272/2008 and should therefore be classified as follows:

R22 Harmful if swallowed

Acute oral category2, H302 Harmful if swallowed.

No classification is required with respect to dermal toxicity.