Phenol, C14-18-alkyl derivs.

Endpoint summary

Description of key information

No toxicokinetic studies are available that directly address absorption, distribution, metabolism, or excretion of C14-16-18 Alkyl phenol (EC Number: 931-468-2) following oral administration; however information is available from existing toxicology studies and the physical chemical properties to infer potential toxicokinetic properties.

Key value for chemical safety assessment

Absorption rate - oral (%):

50

Absorption rate - dermal (%):

50

Absorption rate - inhalation (%):

100

Additional information

C14-16-18 Alkyl phenol (EC Number: 931-468-2) is a Substance of Unknown or Variable composition, Complex reaction products or Biological materials(UVCB substance) in which the linear alkyl chain ranges between C14-18, with prevalent substituent being C16, followed by C18 and C14. It is a slightly viscous, clear amber liquid at room temperature, poorly soluble in water (0.026 mg/L) and with a LogP_OW value greater than 7.2. The molecular weight of its major constituents ranges between 290-347 g/mol and its vapour pressure is low (4.8 x 10^-3 Pa at 20°C).

 

Absorption

 

Oral

In an acute oral toxicity study performed according to theAcute Toxic Class Method, no mortality was observed within the 2 groups of animals treated at 2000 mg/kg bw, and only signs of unspecific toxicity or discomfort (hunched posture and piloerection) were observed up to 2 days after dosing. In repeated-dose oral toxicity studies (i.e. a 28-day study and an OECD 421 study), performed by gavage at dosages up to 300 mg/kg bw/day, no treatment-related mortality occurred. Signs of irritation at the portal-of-entry were 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 the 28-day toxicity study, some indications of liver involvement were noted as increases in liver weight and slight changes in clinical biochemistry parameters (i. e. higher alanine aminotransferase, lower total protein and cholesterol level) at the high dose level only. Alkaline phosphatase activity was higher in some individual animals only. Although there was no morphological evidence of liver damage, the higher alanine aminotransferase activity and the increase in liver weight were considered to reach adversity at 300 mg/kg/day.  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.

 

Inhalation

Because the substance is a slightly viscous, clear amber liquid and has a low vapour pressure, it is unlikely to form aerosols, droplets or particles of inhalable size during its normal uses. 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 ofquantitative information, complete absorption (100%) following inhalation is assumed for the purposes of risk assessment.

 

Dermal

The substance is a skin sensitizer; signs of local irritation also extending to areas adjacent to the treated site were observed during the observation period following application for 24 hours in the acute dermal toxicity study. Both these properties can enhance penetration however, the poor water solubility and high LogP_OW value all indicate that absorption through the skin would be limited. In the acute dermal toxicity study signs of systemic toxicity (lethargy, flat posture, shallow respiration, chromodacryorrhoea (snout) and/or ptosis) were also noted between days 1 and 3, thus suggesting that some absorption occurred. As dermal absorption cannot be more than oral absorption, the same value of 50% is assumed 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 P_owvalue suggests a higher concentration inside the cells, especially those of fatty and adipose tissues, rather than in the extracellular compartment. 

 

Metabolism and excretion

The material did not biodegrade in and OECD 301B ready biodegradation study. Extensive metabolism and cleavage is unlikely. Direct sulfate and glucuronic acid conjugations are detoxifying mechanisms that represent the bulk of phenol metabolism; in addition, oxidation by liver cytochromes to hydroquinone or catechol metabolites, which also can undergo conjugation reactions, represents an additional minor metabolic pathway. Conjugated products will be excreted mainly in the urine. Any unchanged material will be excreted via the faeces; based on the molecular weightbetween 290-347 g/mol, excretion via the bile is also likely to occur.