4-(3-phenylpropyl)pyridine

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

Remarks:

paper review of available data

Type of information:

other: paper review of available data

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: paper review of available data

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Literature review of available data

GLP compliance:

no

Test material

Test material information

Constituent 1

Test material form:

liquid

Details on test material:

Yellowish Brown Liquid

Radiolabelling:

no

Results and discussion

Main ADME results

Type:

absorption

Results:

Oral absorption estimated at > 70%. Dermal absorption estimated at < 20%. Inhalation absorptiion is estimated to be low, < 10%.

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Oral absorption estimated at > 70%. Dermal absorption estimated at < 20%. Low to moderate passage into epidermis is possible but acutal studies in mammals to not necessarily confirm it is systemically absorbed. Inhalation absorption is estimated to be low, < 10%, as the substance is not volatile.

Details on distribution in tissues:

Repeat dose toxicity studies in rats indicate distribution of 4-PPP to various organs following oral administration. The lack of reported CNS effects indicates that 4-PPP may not cross the blood brain barrier. Reproductive toxicity data suggests that 4-PPP may cross the placental barrier. Water solubility and partitioning into octanol of 4-PPP indicates that it is likely to accumulate in body fats or breast milk.

Details on excretion:

The major routes of excretion for substances from the systemic circulation are the urine and/or the feces (via bile and directly from the GI mucosa).

Metabolite characterisation studies

Metabolites identified:

no

Details on metabolites:

The substance is a pyridine derivative and, as such, is anticipated to be metabolised extensively. C- and N-oxidation and also N-methylation are expected.

Any other information on results incl. tables

4-PPP is readily absorbed in the through the gastrointestinal tract, less so by dermal absorption and minimally following inhalation. 4-PPP is widely distributed to tissues with the primary tissues being highly perfused including, testes, liver, thyroid gland, adrenal gland and kidney, all of which are considered target organs of toxicity. 4-PPP likely distributed to fat and breast milk, based on their physico-chemical properties. It likely crosses the placental but not the blood-brain barrier. Since 4-PPP contains a pyridine group it is likely to undergo metabolism by cytochrome P450 enzymes. The primary route of metabolism based on pyridine data is N-methylation and N-oxidation. Metabolism is variable between species but pyridine-N-oxide and N-methylpyridinium appear to be the primary metabolites in both animal and human studies of pyridine. Based on genotoxicity studies using metabolic activation systems, metabolites of 4-PPP are not genotoxic. 4-PPP and potential metabolites are excreted primarily in the urine.

Applicant's summary and conclusion

Conclusions:

The substance may be orally absorbed, approximately 70%, and distributed to various tissues. It is likely metabolised in a manner similar to pyridine and excreted in urine and feces. The dermal absorption is low, < 20%, and the inhalation absorption is also likely low based on low volatility.