Benzoic acid, 2-hydroxy-, C14-18-alkyl derivs.

Endpoint summary

Description of key information

The substance is expected to have an oral absorption of 50%, a dermal absorption of 25% and an inhalation absorption of 100%.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

50

Absorption rate - dermal (%):

25

Absorption rate - inhalation (%):

100

Additional information

Introduction

The physico-chemical properties and the results of in vitro studies and acute and repeat dose toxicity studies with animals for benzoic acid, 2-hydroxy-,C14-18 alkyl derivs.,have been used to determine a toxicokinetic profile.

 

Physicochemical properties

The substance, benzoic acid, 2-hydroxy-,C14-18 alkyl derivs., is a clear brown viscous liquid. It is sparingly water soluble (45.7 ± 4.3 µg/L at 20 °C (Wildlife International Ltd., 2010)) with a logP value of 4.54 ± 0.11 at 40 °C (Wildlife International Ltd., 2010). Benzoic acid, 2 -hydroxy-,C14-18 alkyl derivs. contain a carboxylic acid and are therefore weakly acidic in nature, with a pH of 1.7 (1 M) and pKa of 3.4 at 20 °C (Shell International Petroleum Co., 1998). Benzoic acid, 2-hydroxy-,C14-18 alkyl derivs. are hydrolytically stable at pH 4, 7 and 9 at 50 °C for five days (Shell International Petroleum Co., 1998). Table 1 presents a summary of the physicochemical properties.

Table 1: Chemical Properties

Property	benzoic acid, 2-hydroxy-,C14-18 alkyl derivs.	Reference
Water solubility	46 µg/L	(Wildlife International Ltd., 2010)
LogP	4.54 at 40 °C	(Wildlife International Ltd., 2010)
pH (1M)	1.7	Calculated
pKa	3.4 at 20 °C	(Shell International Petroleum Co., 1998)
Hydrolysis	Stable	(Shell International Petroleum Co., 1998)

 

Absorption

Oral absorption

An acute oral study (Latour, Report No. 506481, 2014) indicates that uptake does occur, with some systemic signs being noted at the administered dose (2000 mg/kg). In the 28 day study (Beerens-Heijnen, 2015) a NOAEL of 100 mg/kg bw/day was obtained, again indicating that oral uptake does occur. Very little on the quantitative value of oral absorption can be inferred from these studies. The substance has a molecular weight < 500, which is favourable for uptake. A pKa of 3.4 means that the substance is likely to be protonated in the stomach (pH 2-3) where some absorption can occur, but in the intestines (pH 5-9) where absorption is most common it will be deprotonated, making absorption less likely. The substance is also highly lipophilic (logP 4.54) and has low water solubility (46 µg/L), and this too may limit absorption. In the absence of quantitative data oral absorption is set to 50% for the purposes of risk assessment.

 

Dermal absorption

Benzoic acid, 2-hydroxy-,C14-18 alkyl derivs. causes slight skin irritation (Pharmaco LSR Ltd., 1995), is a skin sensitiser (Pharmaco LSR Ltd., 1995) and showed slight toxic signs during an acute dermal toxicity test (Latour, Report No. 506482, 2014), indicating that dermal absorption has occurred. However, the extent to which dermal absorption occurs is unclear. Therefore, for the purposes of risk assessment estimation of mammalian dermal absorption is made in accordance with principles adopted by the EFSA guidance on estimating dermal absorption of pesticide active substances (EFSA, 2012). On this basis, dermal absorption for the substance is assumed to be 25%.

 

Inhalation absorption

In the absence of quantitative information, complete absorption (100%) following inhalation is assumed for the purposes of risk assessment.

 

Distribution

It can be expected that once absorbed the substance will be widely distributed throughout the body.

 

Metabolism

There is no metabolism data available for this substance. Conjugation is likely to occur, which will increase the water solubility and make the substance easier to excrete. There is considered to be no potential for bioaccumulation.

 

Elimination

Although there is no elimination data available for this substance, compounds with a molecular weight > 300 tend to be excreted in the bile, not the urine.