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Description of key information

The study performed was an acute oral toxicity test to the rat, following an up-and-down procedure in accordance with the OECD guideline nĀ°425, EPA Health Effects Test Guidelines OPPTS 870.1100 and a guideline from Japanese Ministry of Agriculture, Forestry and Fisheries (Test Data for Registration of Agricultural Chemicals, Acute oral toxicity (2-1-1), 12 Nousan No 8147, Agricultural Production Bureau, November 24, 2000.). The acute median lethal oral dose (LD50) of JNJ-31052047-ABI to rats was demonstrated to be 2000 mg/kg bodyweight.

Key value for chemical safety assessment

Acute toxicity: via oral route

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

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The study was performed to assess the acute oral toxicity of JNJ-31052047-ABI, to the rat.

One fasted female rat received a single oral gavage dose of the test substance, formulated in polyethylene glycol 400 (PEG400), 1.2 eq NaOH 10N and 0.3 eq HCI 12 N, at a dose level of 175 mg/kg bodyweight. No clinical signs were seen in this animal.

As this animal did not die, a further fasted female was then similarly dosed at 550 mg/kg bodyweight.

A third female was dosed at 2000 mg/kg bodyweight. Clinical signs seen prior to death comprised unsteady gait, flat posture, irregular breathing, underactivity, reduced body temperature, piloerection, reduced body tone, hindlimbs splayed, convulsion, shallow

breathing, partially closed eyelids, increased body tone, prominent eyes, salivation and fast breathing. These signs were seen from approximately five minutes after dosing. The animal lost weight during the study. Macroscopic examination revealed congestion (darkened tissues/organs) of the subcutaneous tissue, pallor of the liver, spleen and kidneys, a small stomach and fluid (yellow or green) in the stomach, duodenum, and small and large intestines.

Due to the death of this animal, the next female was dosed at 550 mg/kg bodyweight . As this animal survived, a further three groups of one fasted female were similarly dosed at 2000 mg/kg bodyweight to complete the study.

No clinical signs were seen in the animal dosed at 175 mg/kg or 550 mg/kg except for one 550 mg/kg female. Clinical signs seen in the female were confined to dark faeces, seen from approximately three hours after dosing and resolved by Day 2. Clinical signs observed in the surviving animals dosed at 2000 mg/kg comprised unsteady gait, irregular breathing, underactivity, reduced body temperature, piloerection, elevated gait, hunched posture, flat posture, reduced body tone, hindlimbs splayed, convulsions, thin build, damaged eye, decreased faecal pellets and post salivation staining. These signs were seen from approximately three hours after dosing or on Days 3 or 5 and all signs had resolved in one animal on Day 13 but the other two animals were still showing signs at termination on Day 15.

A loss in bodyweight was observed between Days 1 and 8 for two animals dosed at 2000 mg/kg and no bodyweight gain was noted between Days 1 and 8 for the remaining animal dosed at 2000 mg/kg.

Macroscopic examination of the surviving animals on Day 15 revealed pallor of the liver and kidneys of one female dosed at 2000 mg/kg

The acute median lethal oral dose (LD50) of JNJ-31052047-ABI to rats was then demonstrated to be 2000 mg/kg bodyweight.


Justification for selection of acute toxicity ā€“ oral endpoint
Only one study available

Justification for classification or non-classification

Based on the results of the acute oral toxicity test in rats and according to the criteria of the DSD and CLP Regulation, the substance is classified as R22 and as acute oral toxic category 4 (H302).