Registration Dossier

Administrative data

Link to relevant study record(s)

Reference
Endpoint:
basic toxicokinetics, other
Type of information:
other: Literature review
Adequacy of study:
key study
Study period:
2016-12-07
Reliability:
other: not applicable
Rationale for reliability incl. deficiencies:
other: Literature review to assess basic toxicokinetics of nicotine covered by this registration. For this review literature from official authorities, peer reviewed journals and others were used.
Conclusions:
Absorption of nicotine depends on pH. Several variables are influencing the pharmacokinetics and pharmacodynamics of nicotine, e.g. the efficacy of metabolism, the rapidity of uptake, potential physiological effects of nicotine metabolites and nicotine excretion. The major route by which nicotine enter the body is via the lung. When nicotine is dosed orally or i.p., first-pass metabolism and its effect on the relative dose exposure to nicotine must be considered. Due to the fact that nicotine t1/2in rodents is generally shorter than in primates/humans necessitates the use of higher daily doses of nicotine in rodent models to achieve the nicotine concentration comparable to those seen in smokers.

Description of key information

Assessment of toxicokinetics was made on base of a literature review.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

Default values for bioavailability for the same exposure route in animals and humans are used for chemical safety assessment:

-oral-to-oral extrapolation: 1 (=100%/100%)

-dermal-to-dermal extrapolation: 1 (=100%/100%)

-inhalation-to-inhalation extrapolation: 1 (=100%/100%)

Default values for route-to-route extrapolation:

-oral-to-inhalation extrapolation: 0.5 (=50%/100%)

-inhalation-to-oral extrapolation: 1 (=100%/100%)

-oral-to-dermal extrapolation: 1 (=100%/100%)

-dermal-to-oral extrapolation: 1 (=100%/100%)

-inhalation-to-dermal extrapolation: 1 (=100%/100%)