Compendium of the most significant studies with reference to properties, intake, effects.

Johnson W, Bergfeld WF, Belsito DV, Hill RA, Klaassen CD, Liebler DC, Marks JG, Shank RC, Slaga TJ, Snyder PW, Andersen FA. Safety Assessment of Benzyl Alcohol, Benzoic Acid and its Salts, and Benzyl Benzoate. Int J Toxicol. 2017 Nov/Dec;36(3_suppl):5S-30S. doi: 10.1177/1091581817728996. 

Abstract. Benzyl alcohol, benzoic acid and its salts, and benzyl benzoate function mostly as fragrance ingredients/preservatives in cosmetic products. The Cosmetic Ingredient Review Expert Panel previously established concentration limits for benzyl alcohol, benzoic acid, and sodium benzoate in cosmetics and determined that the available data were insufficient to support the safety of these ingredients during inhalation exposure. After reviewing newly available data, it was concluded that benzyl alcohol, benzoic acid and its salts, and benzyl benzoate are safe in the present practices of use and concentration described in this safety assessment.

Wilson L, Martin S. Benzyl alcohol as an alternative local anesthetic. Ann Emerg Med. 1999 May;33(5):495-9. doi: 10.1016/s0196-0644(99)70335-5.

Abstract. Study objectives: Benzyl alcohol has been used as a local anesthetic for brief superficial skin procedures; however, its efficacy for long-term cutaneous anesthesia has not been established. We sought to compare the cutaneous anesthetic effects of benzyl alcohol with epinephrine with the effects of lidocaine with epinephrine and with placebo.....Conclusion: Benzyl alcohol with epinephrine provides prolonged cutaneous anesthesia, although it is not as effective as lidocaine with epinephrine. However, benzyl alcohol is significantly less painful on injection than lidocaine with epinephrine, and it may offer an alternative for local anesthesia.

Lam XM, Patapoff TW, Nguyen TH. The effect of benzyl alcohol on recombinant human interferon-gamma. Pharm Res. 1997 Jun;14(6):725-9. doi: 10.1023/a:1012190120061.

Abstract. Purpose: The goal of this study was to investigate the conformational change and aggregation of recombinant human interferon-gamma (rhIFN-gamma) as a result of interaction between benzyl alcohol and the protein. The effects of buffer concentration, buffer species, ionic strength, rhIFN-gamma and benzyl alcohol concentrations on the dynamics of the interaction in liquid formulations were also examined....Conclusions: Interaction between benzyl alcohol and rhIFN-gamma is formulation dependent. Protein concentration, buffer species, buffer concentration, and preservative concentration play a significant role in determining the extent of the interaction and consequently the stability of the product.

Kawai T, Yamauchi T, Miyama Y, Sakurai H, Ukai H, Takada S, Ohashi F, Ikeda M. Benzyl alcohol as a marker of occupational exposure to toluene. Ind Health. 2007 Jan;45(1):143-50. doi: 10.2486/indhealth.45.143. 

Abstract. Benzyl alcohol (BeOH) is a urinary metabolite of toluene, which has been seldom evaluated for biological monitoring of exposure to this popular solvent. The present study was initiated to develop a practical method for determination of BeOH in urine and to examine if this metabolite can be applied as a marker of occupational exposure to toluene. A practical gas-liquid chromatographic method was successfully developed in the present study with sensitivity low enough for the application (the limit of detection; 5 microg BeOH /l urine with CV=2.7%). Linearity was confirmed up to 10 mg BeOH/l, the highest concentration tested, and the reproducibility was also satisfactory with a coefficient of variation of 2.7% (n=10). A tentative application of the method in a small scale study with 45 male workers [exposed to toluene up to 130 ppm as an 8-h time-weighted average (8-h TWA)] showed that BeOH in the end-of-shift urine samples was proportional to the intensity of exposure to toluene. The calculated regression equation was Y=50+1.7X (r=0.80, p<0.01), where X was toluene in air (in ppm as 8-h TWA) and Y was BeOH in urine (in microg/l of end-of-shift urine). The levels of BeOH in the urine of the non-exposed was about 50 microg/l, and ingestion of benzoate as a preservative in soft drinks did not affect the BeOH level in urine. The findings as a whole suggest that BeOH is a promising candidate for biological monitoring of occupational exposure to toluene.

Jaeschke H, Du K. Benzyl Alcohol: A novel treatment for acetaminophen overdose? Hepatology. 2015 Nov;62(5):1641-2. doi: 10.1002/hep.27786. 

Abstract. We read with interest the recent paper by Cai et al. suggesting that “benzyl alcohol (BA) may prove to be a useful adjunct in the treatment of APAP and other forms of sterile liver injury”.1 We would like to point out a few reasons why BA will not likely be a clinically useful therapeutic option for APAP overdose patients. First, as the authors discussed themselves,1 BA can inhibit mitochondrial respiration and is toxic at higher doses. Second, 100 μM BA was shown to inhibit the enzyme activities of Cyp1A2, Cyp2E1 and Cyp3A4 by 20–50%.2 Since the authors used about 9 mM BA for the in vitro experiments and exposed the liver to mM concentrations in vivo,1 the protective effect was most likely caused by P450 inhibition. This conclusion is supported by the almost 100% protection in vivo and the fact that BA was most effective when given during a narrow window around the time of APAP treatment, which confirms that BA only protects when present during the metabolism phase of APAP. However, the established clinical antidote N-acetylcysteine is most effective during the metabolism phase and beyond with lower risk. Third, the authors argue about an inhibitory effect of BA on the inflammasome.1 Interestingly, all studies that investigated a role of the Nalp3 inflammasome and interleukin-1β (IL-1β) in APAP hepatotoxicity are in agreement that damage-associated-molecular-patterns released from necrotic cells activate macrophages to generate cytokines including pro-IL-1β.1,3,4 All groups also agree that inhibition or deficiency of caspase-1 eliminates processing of pro-IL-1β to the active cytokine.1,3,4 Most importantly, all agree that only a few pg/ml IL-1β are actually produced during APAP hepatotoxicity.1,3,4 However, the fact that mice treated with 10,000-fold more recombinant IL-1β had no effect on APAP-induced liver injury clearly indicates that minor quantities of endogenously generated IL-1β have no impact on APAP hepatotoxicity.4 Thus, there is little chance that the inflammasome and IL-1β will be clinically relevant targets. Case in point, in APAP overdose patients there is no significant IL-1β formation [Control: 3.8±0.5 pg/ml (n=3); APAP: 5.5±1.7 pg/ml (n=10)] and neutrophils do not contribute to the injury.10

Geier J, Ballmer-Weber B, Buhl T, Rieker-Schwienbacher J, Mahler V, Dickel H, Schubert S; IVDK. Is benzyl alcohol a significant contact sensitizer? J Eur Acad Dermatol Venereol. 2022 Jun;36(6):866-872. doi: 10.1111/jdv.17968. 

Abstract. Background: Benzyl alcohol is a widely used preservative, solvent and fragrance material. According to published data, it is a rare sensitizer in humans. Objectives: To identify characteristics and sensitization patterns of patients with positive patch test reactions to benzyl alcohol and to check the reliability of the patch test preparation benzyl alcohol 1% pet....Conclusions: Sensitization to benzyl alcohol occurs very rarely, mainly in patients with stasis dermatitis. In view of our results, benzyl alcohol cannot be regarded as a significant contact allergen, and therefore marking it as skin sensitizer 1B and labelling it with H 317 is not helpful. © 2022 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.

Meinking TL, Villar ME, Vicaria M, Eyerdam DH, Paquet D, Mertz-Rivera K, Rivera HF, Hiriart J, Reyna S. The clinical trials supporting benzyl alcohol lotion 5% (Ulesfia): a safe and effective topical treatment for head lice (pediculosis humanus capitis). Pediatr Dermatol. 2010 Jan-Feb;27(1):19-24. doi: 10.1111/j.1525-1470.2009.01059.x. 

Abstract. Benzyl alcohol lotion 5% (BAL 5%) is a non-neurotoxic topical head lice treatment that is safe and effective in children as young as 6 months of age. The safety and efficacy of this pediculicide has been studied in 695 (confirm number) subjects in all phases of clinical development. Scanning electron micrographs (SEM) demonstrated that the active agent appears to stun the breathing spiracles open, enabling the vehicle to penetrate the respiratory mechanism (spiracles), therefore asphyxiating the lice. Initial phase II trials compared this novel product to RID using identical volumes of treatment (4 oz/application) and yielding, almost, identical efficacy. This outcome pointed to the significant importance of completely saturating the hair with the product in order to achieve maximum treatment success. A second phase II trial, which allowed the use of sufficient product to saturate the hair, resulted in 100% efficacy after both 10 and 30 minute treatments. A third phase II trial verified an effective dose. Phase III trials compared BAL 5% to vehicle placebo for two 10-minute applications. It proved to be safe and effective (p < 0.001) for treatment of head lice and is the first FDA-approved non-neurotoxic lice treatment, now available in the United States as Ulesfia lotion.

Cole LK, Luu DH, Rajala-Schultz PJ, Meadows C, Torres AH. In vitro activity of an ear rinse containing tromethamine, EDTA, and benzyl alcohol on bacterial pathogens from dogs with otitis. Am J Vet Res. 2006 Jun;67(6):1040-4. doi: 10.2460/ajvr.67.6.1040. 

Abstract. Objective: To evaluate the in vitro activity of an ear rinse (ER) containing tromethamine, EDTA, and benzyl alcohol on bacterial pathogens from dogs with otitis....Conclusions and clinical relevance: On the basis of results of this study, future studies should be performed to evaluate the in vivo efficacy of ER alone as a treatment for otic infections caused by beta-hemolytic streptococcus, P aeruginosa, and Proteus spp and of ER combined with an antimicrobial agent for otic infections caused by Staphylococcus spp.