A 28-Day Repeated Dose Toxicity Study of Ultraviolet Absorber 2-(2′-Hydroxy-3′,5′-di-tert-butylphenyl) benzotriazole in Rats

Abstract

To examine the possible repeated-dose toxicity of an ultraviolet absorber, 2-(2'-hydroxy-3',5'-di-tert-butylphenyl)benzotriazole (HDBB), CD(SD)IGS rats were administered HDBB by gavage at a dose of 0 (vehicle: corn oil), 0.5, 2.5, 12.5, or 62.5 mg kg(-1) day(-1) for 28 days. At the completion of the administration period, a decrease in red blood cells, hemoglobin, and hematocrit was noted only in males at 2.5 mg/kg and more. Blood biochemical changes were noted at 0.5 mg/kg and more in males and at 62.5 mg/kg in females. Histopathologic changes were observed principally in the liver (vacuolar degeneration and hypertrophy of hepatocytes, bile duct proliferation, etc.) and in the heart (degeneration and hypertrophy of myocardium and cell infiltration). These changes were noted at 0.5 mg/kg and more in males and at 12.5 mg/kg and more in females. At higher doses, hypertrophy of tubular epithelium in the kidneys and diffuse follicular cell hyperplasia in the thyroids in both sexes and increased severity of basophilic tubules in the kidneys and extramedullary hematopoiesis in the spleen in males were also detected. After the 14-day recovery period, these changes mostly recovered in females but not in males. Based on these findings, no observed adverse effect level (NOAEL) was concluded to be less than 0.5 mg kg(-1) day(-1) in male rats and 2.5 mg kg(-1) day(-1) in female rats.

Gonadal Influence on the Toxicity of 2-(2′-Hydroxy-3′,5′-di-tert-butylphenyl) benzotriazole in Rats

“…Previously, we showed a marked difference in the susceptibility of male and female rats to the toxicity of HDBB in 28-day and 52-week repeated oral dose toxicity studies (Hirata-Koizumi et al, 2007;2008). In the 28-day study, toxic effects in the liver, heart, kidneys, thyroids, and blood were observed.…”

Synthetic musk compounds and benzotriazole ultraviolet stabilizers in breast milk: Occurrence, time–course variation and infant health risk

“…The HBT and its methylated HBT inhibited growth and reproduction of water plants and aquatic invertebrates (Seeland et al, 2012). In particular, UV-320 showed histopathological changes in heart, liver, and kidney in rats (Hirata-Koizumi et al, 2007. Due to toxicological evidence and environmental occurrence, the production, use, and import of UV-320 in Japan has been banned since 2007 ) and UV-320 and -328 were nominated as substances of very high concern (SVHC) in the EU (European Chemicals Agency, 2014).…”

Occurrence and removal of benzotriazole ultraviolet stabilizers in a wastewater treatment plant in China.

“…19 Similar gender-related hematological and histopathological changes were also observed for UV-320 in rats. 20 Generally, full scale WWTPs comprise physical and biochemical treatment systems. In the physical treatment process, sludge adsorption is usually the major removal mechanism, while the effectiveness of some organic chemical elimination is related to the biodegradation processes in the secondary treatment unit.…”