Abstract

1. Phenolic benzotriazoles are ultraviolet-light absorbers used in a variety of industrial and consumer applications. We investigated the toxicokinetic behaviour of 9 compounds, covering unsubstituted, monosubstituted, disubstituted, and trisubstituted compounds, following a single gavage (30 and 300 mg/kg) and intravenous (IV) (2.25 mg/kg) administration in male rats.

2. Following IV administration, no distinct pattern in plasma elimination was observed for the compounds with half-lives ranging from 15.4–84.8 h. Systemic exposure parameters, maximum concentration (C_max) and area under the concentration time curve (AUC), generally increased with the degree of substitution.

3. Following gavage administration, C_max and AUC of unsubstituted compound were lower compared to the substituted compounds. C_max and AUC increased ≤7-fold with a 10-fold increase in the dose except for the AUC of the unsubstituted compound where the increase was 30-fold. Plasma elimination half-lives for the class ranged from 1.57 to 192 h with the exception of 30 mg/kg drometrizole.

4. Oral bioavailability was low with ∼ 6% estimated for unsubstituted compound and 12.8–23% for others at 30 mg/kg dose. Bioavailability was lower following administration of the higher dose.

5. Taken collectively, these data point to low oral absorption of phenolic benzotriazoles. The absorption decreased with increasing dose. Substituted compounds may be less metabolized compared to the unsubstituted.

摘要

1. 酚醛苯并三唑是用于各种工业和消费应用的紫外线吸收剂。我们研究了 9 种化合物的毒代动力学行为，包括未取代、单取代、二取代和三取代化合物，在雄性大鼠中单次灌胃（30 和 300 mg/kg）和静脉内 (IV) (2.25 mg/kg) 给药后。

2. IV 给药后，半衰期为 15.4-84.8 小时的化合物没有观察到明显的血浆消除模式。全身暴露参数、最大浓度 (C _max ) 和浓度时间曲线下面积 (AUC) 通常随着取代程度的增加而增加。

3. 管饲给药后，未取代化合物的 C _max和 AUC 低于取代化合物。C _max和 AUC 随着剂量增加 10 倍而增加≤7 倍，但未取代化合物的 AUC 增加了 30 倍。该类的血浆消除半衰期为 1.57 至 192 小时，30 mg/kg 甲曲唑除外。

4. 口服生物利用度低，未取代化合物估计为 6%，其他 30 mg/kg 剂量为 12.8-23%。施用较高剂量后生物利用度较低。

5. 综上所述，这些数据表明酚类苯并三唑的口服吸收率低。吸收随剂量增加而减少。与未取代的相比，取代的化合物可能较少被代谢。