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4-methylanisol has a molecular weight of 122 g/mol and is present as a liquid with a low volatility (0.1 kPa at 17 °C). It is moderately lipophilic with a logPow of 2.8 and shows a low water solubility.

Based on the oral acute and repeated dose studies, systemic availability 4-methylanisol is expected after oral or inhalative exposition, although the low volatility of 4-methylanisol does not imply the inhalation to be a relevant route of exposure.

 

Mortality in rats has been reported after single oral administration via gavage using corn oil as vehicle (RIFM1971) and single oral application in mice resulted in mortality, clinical and necropsy findings (Givaundan MT1971). Administration of 4-methylanisol in olive oil for 4 weeks to Wistar rats via gavage resulted in changes of clinical chemical parameters and adverse liver effects (Key.BASF21C0810/89101). Evidences for systemic availability via the oral route can further be derived from the general systemic and developmental toxicity observed in an oral reproduction/ developmental toxicity screening test in rats (BASF90R0506/09068).

 

Concerning the potential of 4-methylanisol to penetrate through skin, a dermal absorption study is available as short summary from a secondary source (Hawkins 1993). Groups of 4 male Sprague-Dawley rats were treated topically (occlusive) with a single doss of (14)C-4-methylanisole (100, 320, 1000 mg/kg bw in diethyl phthalate) for 6 hours. After 72 hours, total urinary excretion accounted for about 12% dose in rats dosed at 100 & 320 mg/kg and about 20% dose in rats dosed at ca. 1000 mg/kg. Total excretion in faeces accounted for 0.05-0.17% of the applied dose at all dose levels. Radioactivity in expired air accounted for about 11, 23 & 37 for 100, 320 and 1000 mg/kg bw respectively. Overall, the bioavailability via dermal route can be estimated to be approx. 23%, 35%, 57% of the applied dose (100, 320 and 1000 mg/kg bw respectively).

 

Based on its molecular weight and moderate lipophilicity, a certain cellular uptake in eg. adipose tissues is expected. Distribution into the liver is assumed based on the adverse effects seen in the oral repeated dose study.

 

As putative metabolisation for aromatic ethers, one or more of three pathways, i.e. ring hydroxylation, O-dealkylation, or side-chain oxidation would be expected followed by a conjugation with glucuronic acid, sulfate or glycine. After a single oral dose of 4-methylanisole to rabbits, anisic acid (mainly as ester glucuronide and anisuric acid) and p-cresol was excreted in the urine (Bray 1955).

 

Based on its log Po/w, low water solubility and the evident excretion after dermal application , bioaccumulation of 4-methylanisol is considered to be unlikely.