Final Report on the Safety Assessment of Azulene

Abstract

Azulene is an extract from the volatile oil of several perennial herbs and is detected in tobacco smoke. It functions as a skin conditioning agent in cosmetic formulations, including hair dyes. Azulene is reported to be used in a wide range of cosmetic formulations, but these reported uses are likely to be uses of guaiazulene, a chemically related colorant, because there are currently no suppliers of Azulene to the cosmetics industry. The anti-inflammatory action of Azulene has been demonstrated in several animal studies. Effects at the cellular level are reported to include inhibition of respiration and growth, but no effect on ciliary activity or membrane permeability. Relatively low oral toxicity was seen in acute animal studies. Azulene was not mutagenic in an Ames test, with and without metabolic acfivation. An allergic response to Azulene was noted in one case report. These data were clearly insufficient to support the safety of Azulene in cosmetics. Additional data needed to make a safety assessment include: methods of manufacture and impurities, especially naphthalenes; current concentration of use; skin penetration, if there is significant skin penetration, then both a 28-day dermal toxicity study to assess general skin and systemic toxicity and a reproductive and developmental toxicity study are needed; one genotoxicity study in a mammalian system, if positive, then a 2-year dermal carcinogenesis study using National Toxicology Program methods is needed; skin irritation and sensitization in animals or humans; and ocular toxicity.

Photomutagenicity of cosmetic ingredient chemicals azulene and guaiazulene

“…The results presented here suggest that irradiation with relatively harmless UVA and visible sunlight can turn the normally not mutagenic azulene/guaiazulene into mutagenic compounds. Since azulene is so widely used in our daily lives as cosmetic products [3][4][5], its safety needs to be carefully evaluated further. So far, its use has been considered safe because its mutagenicity and acute toxicity are negligible [5,8] and it is even beneficial as a weak anti-inflammatory agent [6].…”

“…When azulene was injected into the brains of rats, it caused non-space-occupying lesions [7]. Azulene was found not mutagenic in Salmonella typhimurium bacteria strains TA98, TA100, TA1535, and TA1537 with and without the presence of an S9 activation enzyme system [5]. In clinical studies, some patients showed allergic reactions to azulene [8].…”

“…Azulene is an essential oil derived from German chamomile plant Matricaria chamomile. In addition to its wonderful aroma, this oil is an anti-inflammatory, anti-spasmodic, and anti-microbial agent [5,6]. Reports from various sources including the United States Food and Drug Administration showed that azulene is a popular ingredient for various products for human uses [3][4][5].…”

“…In addition to its wonderful aroma, this oil is an anti-inflammatory, anti-spasmodic, and anti-microbial agent [5,6]. Reports from various sources including the United States Food and Drug Administration showed that azulene is a popular ingredient for various products for human uses [3][4][5]. Its toxicology to experimental rodents, including mutagenicity and the clinical assessment of its safety, has been reported [5,6].…”

“…Reports from various sources including the United States Food and Drug Administration showed that azulene is a popular ingredient for various products for human uses [3][4][5]. Its toxicology to experimental rodents, including mutagenicity and the clinical assessment of its safety, has been reported [5,6]. When dosed orally, azulene exhibited acute toxicity of LD 50 of 3 g/kg in mice and 4 g/kg in rats, respectively.…”