Repeated dose toxicity

Repeated dose toxicity tests are intended to reveal any physiological and/or anatomo-pathological changes induced by repeated administration of the active substance or combination of active substances under examination, and to determine how these changes are related to dosage.

Repeated dose toxicity (28 days)

Repeated dose toxicity (sub-acute or chronic toxicity)

Repeated dose toxicity Repeated-dose toxicity studies revealed vacuolation of the tubular cells of the kidneys, with strong evidence for reversibility of the effect.

Repeated dose toxicity testing and embryo-foetal toxicity studies are impracticable due to induction of, and interference with antibodies.

Repeated dose toxicity and local tolerance Repeated topical administration of tacrolimus ointment or the ointment vehicle to rats, rabbits and lp

Repeated dose toxicity tests shall be carried out on two species of mammals one of which must be a non-rodent.

Repeated dose toxicity studies in rats identified the liver as the primary target organ for toxicity (increases in transaminases, bile duct hyperplasia, necrosis).

Repeated dose toxicity studies in animals identified major target organs as the liver, retina, thyroid gland and kidney.

Repeated dose toxicity and local tolerance Repeated topical administration of tacrolimus ointment or the ointment vehicle to rats, rabbits and micropigs was associated with slight dermal changes such as erythema, oedema and papules.

Repeated dose toxicity studies of 1, 3 and 6 months duration with telithromycin conducted in rat, dog and monkey showed that the liver was the principal target for toxicity with elevations of liver enzymes, and histological evidence of damage.

Repeated dose toxicity studies of 1, 3 and 6 months duration with telithromycin conducted in rat, dog and monkey showed that the liver was the principal target for toxicity with elevations of liver enzymes, and histological evidence of damage. These effects showed a tendency to regress after i

Repeated dose toxicity studies showed that pramipexole exerted functional effects, mainly involving the CNS and female reproductive system, and probably resulting from an exaggerated pharmacodynamic effect of pramipexole.

Repeated dose toxicity studies in rats and monkeys using doses up to 7-8 mg/ kg given intravenously showed injection site reactions in rats and monkeys, signs of histamine release in rats, and evidence of adverse effects directed at the liver in monkeys.

90-day repeated dose toxicity study

It is also desirable that one of the species is the same as in the repeated dose toxicity studies.

Repeated-dose toxicity

Repeated dose (28 days) toxicity (oral)

REPEATED DOSE (28 DAYS) TOXICITY (ORAL)

If it is proved that systemic absorption is negligible, the repeated dose toxicity tests, the tests for reproductive toxicity and the carcinogenicity tests may be omitted, unless:

Repeated dose (28 days) toxicity (dermal)

REPEATED DOSE (28 DAYS) TOXICITY (DERMAL)

Repeated dose (28 days) toxicity (inhalation)

REPEATED DOSE (28 DAYS) TOXICITY (INHALATION)

repeated dose toxicity,

Repeated dose toxicity.

Repeated-dose toxicity tests are intended to reveal any physiological and/or pathological changes induced by repeated administration of the active substance or combination of active substances under examination, and to determine how these changes are related to dosage.

In the case of substances or medicinal products intended solely for use in non food-producing animals, a repeated dose toxicity study in one species of experimental animal will normally be sufficient.

These studies are recommended for some medicinal products if there is concern about their carcinogenic potential, e.g. from product of the same class or similar structure, or from evidence in repeated dose toxicity studies.

(v) Sub-acute/Sub-chronic toxicity comprises the adverse effects occurring in experimental animals as a result of repeated daily dosing with, or exposure to, a chemical for a short part of their expected lifespan

In the case of new combinations of known substances which have been investigated in accordance with the provisions of this Directive, the repeated-dose tests may, except where toxicity tests have demonstrated potentiation or novel toxic effects, be suitably modified by the investigator, who shall submit his reasons for such modifications.

The repeated dose toxicity test,

Short-term repeated dose toxicity (28 days)

In repeated-dose toxicity studies in rabbits there was no significant evidence of systemic toxicity.

pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction. no

Non-clinical data reveal no special hazard for humans based on studies of single dose toxicity, repeated dose toxicity, and genotoxicity.

Non-clinical data reveal no special hazard for humans based on studies of safety pharmacology, single dose toxicity, repeated dose toxicity and embryonal/ foetal toxicity.

The repeated dose toxicity test, Method B.7, includes assessment of immunotoxic effects.

The repeated dose toxicity test (Methods B.7, B.8 and B.9) includes assessment of toxic effects arising from repeated exposure.

ed Non-clinical data reveal no special hazard for humans based on studies of single dose toxicity, repeated dose toxicity, and genotoxicity.