Butylated Hydroxytoluene Acid Research Articles

Metabolites of 4-methylbenzylidene camphor (4-MBC), butylated hydroxytoluene (BHT), and tris(2-ethylhexyl) trimellitate (TOTM) in urine of children and adolescents in Germany – human biomonitoring results of the German Environmental Survey GerES V (2014–2017)

The UV filter 4-methylbenzylidene camphor (4-MBC), used in cosmetics, the antioxidant butylated hydroxytoluene (BHT), used inter alia as a food additive and in cosmetics, and the plasticizer tris(2-ethylhexyl) trimellitate (TOTM), used mainly in medical devices as substitute for di-(2-ethylhexyl) phthalate (DEHP), are suspected to have endocrine disrupting effects. Human biomonitoring methods that allow for assessing the internal exposure of the general population to these substances were recently developed in a German cooperation to enhance the use of human biomonitoring. First-morning void urine samples from 3- to 17-year-old children and adolescents living in Germany were analysed for metabolites of 4-MBC (N = 447), BHT (N = 2091), and TOTM (N = 431) in the population-representative German Environmental Survey on Children and Adolescents 2014–2017 (GerES V). 4-MBC metabolites were found in quantifiable amounts only in single cases and exposure levels remained well below health-based guidance values. In contrast, ubiquitous exposure to BHT became evident with a geometric mean (GM) urinary concentration of the metabolite BHT acid of 2.346 μg/L (1.989 μg/gcreatinine) and a maximum concentration of 248 μg/L (269 μg/gcrea). The highest GM concentration was found in young children aged 3–5 years, yet no specific sources of exposure could be identified. Also, TOTM metabolites were found in quantifiable amounts only in very few samples. None of these findings could be related to previous hospital treatment or exposure via house dust. The presented results will be the basis to derive reference values for exposure of children and adolescents in Germany to BHT and will facilitate to identify changing exposure levels in the general population.

A biomonitoring study assessing the exposure of young German adults to butylated hydroxytoluene (BHT).

The antioxidant 2,6-di-tert-butyl-4-methylphenol (butylated hydroxytoluene, BHT) is used ubiquitously in food, cosmetics, pharmaceuticals, fuels, plastics, rubbers and many other products. Therefore, exposure of the general population to this substance is likely. We analyzed the BHT metabolite 3,5-di-tert-butyl-4-hydroxybenzoic acid ("BHT acid") in 24-h urine samples from the German Environmental Specimen Bank with the aim of gaining a better understanding of the internal burden of BHT in young nonspecifically exposed adults. The study population consisted of students between 20 and 29 years of age at the time of sampling, all from Halle/Saale in Central Germany. In total, 329 samples collected in the years 2000, 2004, 2008, 2012, 2015, and 2018 were measured by ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). BHT acid was detected above the limit of quantification (0.2μg/L) in 98% of the samples. The median of the measured concentrations was 1.06μg/L and 1.24μg/g creatinine respectively, the median of the daily excretion was 1.76 μg/24h and - additionally normalized for body weight - 26.8 ng/24h×kg bw respectively. The corresponding 90th percentiles were 3.28μg/L, 3.91μg/g creatinine, 5.05 μg/24h, and 81.9 ng/24h×kg bw. Medians of creatinine-corrected values were slightly higher in women than in men, while the opposite situation was observed for the volume concentrations and the 24-h excretion values (not corrected for body weight). Values simultaneously normalized both for 24-h excretion and body weight did not exhibit any significant differences between males and females, probably indicating a virtually identical magnitude of exposure for both genders. The background exposure of the investigated population was found to be largely constant since the year 2000, with only weak temporal trends at most. Daily intakes were estimated from excretion values and found to be largely below the acceptable daily intake (ADI) of BHT at 0.25mg/kg bw: our worst-case estimate is a daily BHT intake of approximately 0.1mg/kg bw at the 95th percentile level. However, these intake assessments rely on very limited quantitative data regarding human metabolism of BHT.

Excretion of dietary butylated hydroxytoluene by the rat

The concentration of phenols in the urine or feces of rats receiving a diet containing 1.00% butylated hydroxytoluene (BHT) for 10 days was determined colorimetrically. The cumulative intake of BHT was approx. 5.0 mmol/rat for 10 days. The total amount of phenols excreted in urine and feces was 3.65 mmol/rat for 10 days, i.e. 73% of the administered BHT. About 48% was excreted in the urine, and 25% in the feces; about 30%, or 11%, of the dose appeared to be present as unconjugated phenols in the urine, or feces, respectively. The major metabolite detected was 3,5-di- tert-butyl-4-hydroxybenzoic acid (BHT acid).