The dose resulting in death was 2400 U/ kg.

(i) LD lethal dose.

The possibility of a lethal intake of granules by small birds cannot be excluded.

(ii) LD 50 (median lethal dose) is a statistically derived single dose of a substance that can be expected to cause death in 50 % of dosed animals.

- dose/mortality curve and slope where permitted by the method of determination;

- dose/mortality curve and slope (where permitted by the method of determination);

- dose/mortality curve and slope (where permitted by the method of determination),

The highest dose level should result in toxic effects but produce no, or few, fatalities.

The sighting study yields information on the dose-toxicity relationship, including an estimate of the minimum lethal dose.

- Discriminating dose is the highest out of the four fixed dose levels which can be administered without causing compound-related mortality (including humane kills).

If the initial dose chosen does not produce severe toxicity, and the next higher level produces mortality, then it will be necessary to investigate one or more intermediate dose levels as appropriate.

LD - lethal dose;

Studies in rabbits reveal a dermal lethal dose of greater than 5 g/kg.

LD50 (median lethal dose) is a statistically derived single dose of a substance that can be expected to cause death in 50 % of dosed animals.

Single dose studies in rodents indicate that the lethal dose is around 300 ppm nitric oxide or greater.

For acute toxicity, the LD50 (median lethal dose) or LC50 (median lethal concentration) value or, where the fixed dose procedure has been used, the discriminating dose shall be derived.

Yellow fever virus1 17 D-204 strain (live, attenuated) …………………….not less than 1000 LD50 units2 1 produced in specified pathogen-free chick embryos 2 The statistically determined lethal dose in 50% of animals tested

dose/mortality curve and slope where permitted by the method of determination;

dose/mortality curve and slope (where permitted by the method of determination);

dose/mortality curve and slope (where permitted by the method of determination),

The PNEC may be calculated by applying an assessment factor to the values resulting from tests on organisms, e.g. LD50 (median lethal dose), LC50 (median lethal concentration), EC50 (median effective concentration), IC50 (concentration causing 50 per cent inhibition of a given parameter, e.g. growth), NOEL(C) (no observed effect level (concentration)), or LOEL(C) (lowest observed effect level (concentration)) or other appropriate methods.

In very serious or life threatening infections, the dosage can be increased to 400 mg three times daily.

The PNEC shall be calculated by applying an assessment factor to the values resulting from tests on organisms, e.g. LD50 (median lethal dose), LC50 (median lethal concentration), EC50 (median effective concentration), IC50 (concentration causing 50 % inhibition of a given parameter, e.g. growth), NOEL(C) (no-observed-effect level(concentration)), or LOEL(C) (lowest-observed-effect level (concentration)).

It shall be calculated by applying an assessment factor to the values resulting from tests on organisms, e.g. LD50 (median lethal dose), LC50 (median lethal concentration), EC50 (median effective concentration), IC50 (concentration causing 50 % inhibition of a given parameter, e.g. growth), NOEL(C) (no-observed-effect level (concentration)), or LOEL(C) (lowest-observed-effect level (concentration)).

No fatalities have been reported and all overdose patients recovered without sequelae.

In case of very serious, life-threatening or recurrent infections the dosage can be increased to 400 mg three times daily.

The higher incidence of death was not associated with olanzapine dose (mean daily dose 4.4 mg) or duration of treatment.

Absence or presence of substance related mortality of the animals dosed at one step will determine the next step, i.e.:

The maximum daily dose in very serious or life-threatening infections can be up to 1200 mg daily, administered as 400 mg three times daily

If the long-term toxicity study is carried out separately, the highest dose level should elicit definite signs of toxicity without causing excessive lethality.

As indicated in point 1.4.2.3, the starting dose should be the one which is likely to produce mortality in at least some of the dosed animals.

If you use more Extavia than you should Giving many times the dose of Extavia recommended for the treatment of multiple sclerosis has not led to life-threatening situations.

Discriminating dose is the highest out of the four fixed dose levels which can be administered without causing compound-related mortality (including humane kills).

No treatment related mortalities were noted in juvenile rats dosed at 1,000 mg/kg darunavir (single dose) on day 26 of age or at 500 mg/kg (repeated dose) from day 23 to 50 of age, and the exposures and toxicity profile were comparable to those observed in adult rats.

No deaths occurred following a single oral administration of montelukast sodium at doses up to 5,000 mg/ kg in mice and rats (15,000 mg/ m2 and 30,000 mg/ m2 in mice and rats, respectively), the maximum dose tested.

As with other benzodiazepines or benzodiazepine-like agents, overdose should not present a threat to life unless combined with other CNS depressants (including alcohol).

Acute toxicity studies employing ioflupane at dosage levels of 0.06 mg/ kg, in excess of 6,500 times the maximum human (70 kg) single dose on a bodyweight basis, failed to reveal any mortality or signs of systemic toxicity in rats or rabbits.

Increased incidence of imperforate anus, hypoplastic tail, edema and limb flexures noted in fetuses of pregnant rats dosed at 100 mg/ kg (approximately 400 times the AUC in humans) were associated with increased embryo-fetal lethality and generalized failure to thrive.

Carglumic acid is secreted in the milk of lactating rats and although developmental parameters were unaffected, there were some effects on body weight / body weight gain of pups breast-fed by dams treated with 500 mg/ kg/ day and a higher mortality of pups from dams treated with 2000/ kg/ day, a dose that caused maternotoxicity.

In a phase II study aimed at evaluating Remicade in congestive heart failure (CHF), higher incidence of mortality due to worsening of heart failure were seen in patients treated with Remicade, especially those treated with the higher dose of 10 mg/ kg (i. e. twice the maximum approved dose).

The educational material should include: • A copy of the SPC • Emphasis that: o Severe haemorrhagic events are more frequent in patients ≥ 75 years of age (including fatal events) or those weighing < 60 kg o Treatment with prasugrel is generally not recommended for patients of ≥ 75 years of age. o If, after a careful individual benefit/ risk evaluation by the prescribing physician, treatment is deemed necessary in the ≥ 75 years age group then following a loading dose of 60 mg, a reduced maintenance dose of 5mg should be prescribed. o Patients weighing < 60 kg should have a reduced maintenance dose of 5mg o The evidence for a 5mg dose is based only on PK/ PD analyses and no clinical data currently exist on the safety of this dose in the at risk sub groups.