4-(3-phenylpropyl)pyridine

Endpoint summary

Link to relevant study record(s)

Reference

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

Objective of study:

toxicokinetics

Qualifier:

no guideline followed

Principles of method if other than guideline:

Literature review of available data

GLP compliance:

no

Radiolabelling:

no

Type:

absorption

Results:

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

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).

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.

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.

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.

Description of key information

Absorbed, distributed and metabolised.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

70

Absorption rate - dermal (%):

20

Absorption rate - inhalation (%):

10

Additional information

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. The substance is rapidly biodegradable in the environment, with 70% degradation in 28 days, and is not bioaccumulative in fish. The conclusion is that the substance is not bioaccumulative.