Propyl 4-hydroxybenzoate

Endpoint summary

Description of key information

Propylparaben is rapidly absorbed, metabolised and eliminated predominantly via urine.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

In accordance with Annex VIII, Column 1, Item 8.8 of Regulation (EC) No. 1907/2006 and with Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance (ECHA, 2012), assessment of the toxicokinetic behavior of propylparaben was conducted to the extent that can be derived from the relevant available information on physico-chemical and toxicological characteristics. In addition, several in vivo studies focusing on metabolism and excretion after oral ingestion and on dermal absorption and metabolism.

Propylparaben is a white solid with a molecular weight of 180.2 g/mol and a median particle diameter of 16.2 µm. It has a water solubility of 500 mg/L at 25 °C, a vapour pressure of 0.00034 Pa at 20 °C and its octanol/water partition coefficient (log Pow) is 2.8.

 

Absorption

In an oral feeding study in male cats, the test substance (168 mg/kg bw) was considered to be rapidly absorbed based on an excretion of about 87% of the test substance within 24 h via urine (Phillips et al., 1978). In a further feeding study in rats, propylparaben and its metabolite p-hydroxybenzoic acid were detected in blood with a maximum after 30 minutes and further metabolites were detected in the urine with maxima between 90 minutes and 4 h (Derache and Gourdon, 1963).

These observations are supported by the fact that substances withmolecular weights below 500 are favorable for oral absorption (ECHA, 2012). Since the molecular weight of propylparaben is 180.2 g/mol, absorption of the molecule in the gastrointestinal tract is likely.

In summary, propylparaben is rapidly absorbed systemically after oral uptake.

 

In a dermal metabolism study on human skin, an experimental flux of 4.77 µg/cm²*h was determined for an aqueous solution of propylparaben (370 mg/L) (Dal Pozzo and Pastori, 1996). Additionally, a QSAR calculation, regarding a water solubility of 500 mg/L, resulted in a comparable flux of 6.98 µg/cm²*h. Usually, this value is considered as indicator for a dermal absorption of 40% (Mostert and Goergens, 2011). Based on new data for propyl paraben provided in Géniès et al 2019, the measured value for skin penetration through human skin is 0.2 ± 0.2%. However due to some limitation of the study the proposed absoption of 3.7% by SCCS is considered appropriately conservative.

Propylparaben has a low vapor pressure (0.00034 Pa at 25 °C), thus indicating a low volatility. In humans, particles with aerodynamic diameters below 100 µm have the potential to be inhaled (ECHA, 2012). Since the mean particle diameter of propylparaben is 16.2 µm, absorption of the test substance after inhalation is possible. Propylparaben is not used in spray processes.

Distribution

In a study in rats, the blood concentration of propylparaben reaches a maximum after 30 minutes and then constantly declines (Derache and Gourdon, 1963). In parallel, urinary metabolites of propylparaben were detected within 30 minutes after administration, indicating a limited distribution and a rapid metabolism of propylparaben.

Due to its rapid absorption, metabolism and excretion, no bioaccumulation potential of propylparaben is expected.

In summary, the available data support distribution and no bioaccumulation potential of propylparaben.

 

Metabolism

The metabolism of propylparaben was investigated in several studies after oral and dermal administration. No species differences in metabolism were observed after oral administration of propylparaben to cats (Phillips et al., 1978), dogs (Jones et al., 1956) and rats (Derache and Gourdon, 1963). After oral administration of 168 – 1000 mg/kg bw, main metabolites detected were p-hydroxybenzoic acid immediately after application of the test substance and p-hydroxyhippuric acid, p-hydroxybenzoic acid and conjugates with glucuronic acid in urine within 4 h after application of the test substance.

In a dermal in vitro study on rat skin, the main metabolite detected wasp-hydroxybenzoic acid (Bando et al., 1997). Within 12 h after application of about 515 mg propylparaben in 2 mL PBS, total amounts of about 200 µg test substance and 400 µg p-hydroxybenzoic acid were recovered in the receptor fluid.

In summary, after oral uptake, propylparaben was rapidly metabolized to p-hydroxybenzoic acid, p-hydroxyhippuric acid and conjugates with glucuronic acid. No species differences were observed. After dermal application, p-hydroxybenzoic acid was detected as main metabolite.

Excretion

Excretion of propylparaben and its metabolites was investigated in several studies in cats, dogs and rats(Phillips et al., 1978; Jones et al., 1956; Derache and Gourdon, 1963).

A rapid excretion of the test substance was noticed within 30 minutes and 72 h after application. The major portion of the parent substance and its metabolites (58-96%) was excreted via urine within 24 h. A minor part was excreted via feces (about 3.5%).

In summary, the data indicate a rapid elimination of the test substance and its metabolites in different species. The main route of excretion is via urine.