Final Report on the Safety Assessment of Benzyl Alcohol, Benzoic Acid, and Sodium Benzoate
Final Report on the Safety Assessment of Benzyl Alcohol, Benzoic Acid, and Sodium Benzoate
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DOI：
10.1080/10915810152630729
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发表时间：
2001-01
影响因子：
2.2
通讯作者：
Bindu Nair
中科院分区：
文献类型：
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作者：
Bindu Nair
苯甲醇是一种芳香醇，广泛用于各种化妆品配方中，作为香料成分、防腐剂、溶剂和降粘剂。苯甲酸是一种芳香酸，在各种化妆品中用作pH调节剂和防腐剂。苯甲酸钠是苯甲酸的钠盐，用作防腐剂，也广泛用于化妆品类型。苯甲醇代谢为苯甲酸，与甘氨酸反应，在人体内以马尿酸的形式排出体外。世界卫生组织规定，苯甲醇、苯甲酸和苯甲酸钠的每日可接受摄入量为5毫克/公斤。根据美国食品和药物管理局，苯甲酸和苯甲酸钠通常被认为是安全的食品。在使用大鼠和小鼠进行的长期接触动物研究中未发现苯甲醇的不良反应。在长期接触苯甲酸和苯甲酸钠的动物研究中，其影响仅限于减少采食量和抑制生长。在一项使用小鼠进行的生殖毒性研究中，注意到对照组和经苯甲醇处理的种群之间存在一些差异，但这些差异仅限于母体体重降低和平均产仔重量降低。另一项研究也指出，与对照组相比，胎儿体重有所下降，但第三项研究显示，对照组和经苯甲醇处理的组之间没有差异。苯甲酸与仓鼠吸收和畸形数量增加有关，但在暴露于苯甲酸钠的小鼠和大鼠的研究中没有发现生殖或发育毒性，同样，苯甲酸在两项大鼠研究中呈阴性。这些成分的遗传毒性试验大多呈阴性，但也有一些试验呈阳性。然而，致癌性研究结果为阴性。临床资料表明，这些成分可产生非免疫性接触性荨麻疹和非免疫性直接接触反应，其特征是出现皮疹、红斑和瘙痒。在一项研究中，5%的苯甲醇引起了反应，在另一项研究中，2%的苯甲酸也引起了同样的反应。然而，苯甲醇在10%时不是增敏剂，苯甲酸在2%时也不是。认识到非免疫反应是严格的皮肤，可能涉及胆碱能机制，得出结论，这些成分可以安全地使用浓度高达5%，但制造商在为婴儿和儿童设计的化妆品配方中使用这些成分时应考虑到非免疫现象。此外，在染发剂中使用10%的苯甲醇被认为是安全的。在得出非免疫反应不值得关注的结论时，考虑了有限的身体暴露、使用时间和使用频率。由于这些成分可能用于各种各样的产品类型，因此吸入可能是一种暴露途径。现有的安全试验被认为不足以支持这些成分在以吸入为接触途径的配方中的安全性。需要吸入性毒性数据来完成可能发生吸入的这些成分的安全性评估。
Benzyl Alcohol is an aromatic alcohol used in a wide variety of cosmetic formulations as a fragrance component, preservative, solvent, and viscosity-decreasing agent. Benzoic Acid is an aromatic acid used in a wide variety of cosmetics as a pH adjuster and preservative. Sodium Benzoate is the sodium salt of Benzoic Acid used as a preservative, also in a wide range of cosmetic product types. Benzyl Alcohol is metabolized to Benzoic Acid, which reacts with glycine and excreted as hippuric acid in the human body. Acceptable daily intakes were established by the World Health Organization at 5 mg/kg for Benzyl Alcohol, Benzoic Acid, and Sodium Benzoate. Benzoic Acid and Sodium Benzoate are generally recognized as safe in foods according to the U.S. Food and Drug Administration. No adverse effects of Benzyl Alcohol were seen in chronic exposure animal studies using rats and mice. Effects of Benzoic Acid and Sodium Benzoate in chronic exposure animal studies were limited to reduced feed intake and reduced growth. Some differences between control and Benzyl Alcohol-treated populations were noted in one reproductive toxicity study using mice, but these were limited to lower maternal body weights and decreased mean litter weights. Another study also noted that fetal weight was decreased compared to controls, but a third study showed no differences between control and Benzyl Alcohol-treated groups. Benzoic Acid was associated with an increased number of resorptions and malformations in hamsters, but there were no reproductive or developmental toxicty findings in studies using mice and rats exposed to Sodium Benzoate, and, likewise, Benzoic Acid was negative in two rat studies. Genotoxicity tests for these ingredients were mostly negative, but there were some assays that were positive. Carcinogenicity studies, however, were negative. Clinical data indicated that these ingredients can produce nonimmunologic contact urticaria and nonimmunologic immediate contact reactions, characterized by the appearance of wheals, erythema, and pruritis. In one study, 5% Benzyl Alcohol elicited a reaction, and in another study, 2% Benzoic Acid did likewise. Benzyl Alcohol, however, was not a sensitizer at 10%, nor was Benzoic Acid a sensitizer at 2%. Recognizing that the nonimmunologic reactions are strictly cutaneous, likely involving a cholinergic mechanism, it was concluded that these ingredients could be used safely at concentrations up to 5%, but that manufacturers should consider the nonimmunologic phenomena when using these ingredients in cosmetic formulations designed for infants and children. Additionally, Benzyl Alcohol was considered safe up to 10% for use in hair dyes. The limited body exposure, the duration of use, and the frequency of use were considered in concluding that the nonimmunologic reactions would not be a concern. Because of the wide variety of product types in which these ingredients may be used, it is likely that inhalation may be a route of exposure. The available safety tests are not considered sufficient to support the safety of these ingredients in formulations where inhalation is a route of exposure. Inhalation toxicity data are needed to complete the safety assessment of these ingredients where inhalation can occur.