Sodium long chain alkyl salicylate

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

No toxicokinetic studies are available that directly address absorption, distribution, metabolism, or excretion of Sodium 2-hydroxy-mono-C14-C18 (even numbered)-alkyl benzoate (EC Number: 701-403-0) following oral administration; however information is available from existing toxicology studies and the physical chemical properties to infer potential toxicokinetic properties.

Sodium 2-hydroxy-mono-C14-C18 (even numbered)-alkyl benzoate (EC Number: 701-403-0) is a multi-constituent substance in which the alkyl chain ranges between C14-18, and the carboxylic acid forms salts with sodium. It is a green-black sticky solid, poorly soluble in water (5.9 mg/L) and with a LogPow value of 7.2. Its molecular weight ranges between 356.0 and 413.0 g/mol and its vapour pressure is low (36 x 10^-5 Pa at 20 °C).

 

Absorption

In an acute oral toxicity study performed according to the Acute Toxic Class Method and using propylene glycol as the vehicle, 2 rats out of the 3 treated at 2000 mg/kg bw died. Instead, at the same dose level no animal died (0/10) in a supporting study where the substance was supplied in mineral oil and administered undiluted. Common for both studies was occurrence of diarrhoea following oral gavage, and of signs of discomfort like hunched posture and piloerection. In addition, lesions in the stomach (several dark red foci in the glandular mucosa and irregular surface of the forestomach) were found in both animals that died, with one of them also presenting gelatinous contents of the gastro intestinal-tract. All these appear related more to local effects rather than high bioavailability. In repeated-dose oral toxicity studies (i.e. a 28-day study and an OECD 421 study), performed by gavage (in propylene glycol) at dosages up to 300 mg/kg bw/day, no treatment-related mortality occurred. Sign of irritation at the portal-of-entry were again noted as an irregular surface of the forestomach at necropsy, and subepithelial granulocytic inflammation and/or hyperkeratosis and/or submucosal oedema noted at histopathology. In addition, in the 28-day toxicity study liver involvement was evidenced by the increases in liver weight and alanine aminotransferase (ALAT) activity, and supported by additional clinical chemistry changes. If any of the substance dissociates in the stomach, the different components would be subjected to differential absorption, depending on their nature. Given the physical form, molecular weights that are generally suitable to absorption, the low water solubility and high liposolubility, micellar solubilisation may play a significant role.

Considering the substance as a whole, moderate oral absorption (50 %) is considered appropriate and will be used for risk assessment purposes.

 

Given that the substance is a sticky solid and has a very low vapour pressure, it is unlikely to form aerosols, droplets or particles of inhalable size. However, some absorption from the gastro-intestinal tract has been evidenced, and also in the case of inhalation exposure micellar solubilisation may play a significant role.

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

 

The substance is severely irritating and considered corrosive to the skin, and is a skin sensitizer. Both these properties can enhance penetration however, the physical form, poor water solubility and high LogPow value all indicate that absorption through the skin would be limited, as supported by the absence of clinical signs other than irritation in the acute dermal toxicity study. As the molecular weight is close but lower than 500, 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) and is assumed to be 25 % for the purposes of risk assessment.

 

Distribution

Once absorbed, it can be expected that the substance will be distributed within the body by the chylomicrons and/or bound to serum albumin and widely distributed. The high log Pow value suggests a higher concentration inside the cells, especially those of fatty and adipose tissues, rather than in the extracellular compartment. 

 

Metabolism and excretion

If any of the substance dissociate in the stomach, sodium salicylate and relevant hydrocarbons will be produced. Sodium released from the salt,will be absorbed from the intestineand enter into the large physiological pool for this electrolyte existing within the body. The salicylic acid will be partially excreted in urine as such or subjected to conjugation (with glucuronic acid or glycine) and excreted in the urine as salicyluric acidor, following oxidation, as gentisic acid.Hydrocarbonswill be used as source of energy within the body or, to some extent, excreted mainly with the bile.

 

References

EFSA Panel on Plant Protection Products and their Residues (PPR); Guidance on Dermal Absorption.

EFSA Journal 2012;10(4):2665. [30 pp.] doi:10.2903/j.efsa.2012.2665

Needs C.J. and Brook P.M. (1985) Clinical pharmacokinetics of the salicylates. Clin. Pharmacokinet. 10(2): 164-177