Paraben Compounds—Part I: An Overview of Their Characteristics, Detection, and Impacts
Abstract
:1. Introduction
2. Paraben Characteristics and Applications
3. Paraben Potential Impacts
3.1. Human Health Impact
3.2. Impacts in Animals
3.3. Toxicological Studies
4. Legislation
4.1. Parabens, Pollutants and Discharge Policies
4.2. Paraben Legislation for Industrial Use in European Union
4.3. Other Paraben Legislation and Considerations Regarding Countries Outside the EU
4.4. Detection of Parabens in Products and Concentration of Use in Industrial Products
5. Paraben Detection
5.1. Detection in Water Soruces
5.1.1. Paraben Detection in WWTPs
5.1.2. Paraben Detection in Water Resources
5.2. Detection in Humans
5.3. Detection in Animals
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Compound | CAS Number | Molecular Formula | Molecular Mass/(g/mol) | Melting Temperature/(°C) | Boiling Temperature/(°C) | Solubility in Water at 25 °C/(mg/L) | Dissociation Constant (pKa) | Octanol-Water Partition (Log Kow) |
---|---|---|---|---|---|---|---|---|
Methylparaben (MP) | 99-76-3 | C8H8O3 | 152.15 | 131 b, c | 270–280 b 275 c | 5981 a 2500 c 2000 d | 8.17 a, b, d | 1.96 a,c 1.66 d |
Ethylparaben (EP) | 120-47-8 | C9H10O3 | 166.17 | 116–118 b 117 c | 297–298 b 297.5 c | 1894 a 885 c 860 d | 8.22 a, b, d | 2.47 a,c 2.19 d |
Propylparaben (PP) | 94-13-3 | C10H12O3 | 180.20 | 96–98 b 97 c | 285.1 c | 529.3 a 500 c 300 d | 8.35 a, b, d | 3.04 a,c 2.71 d |
Butylparaben (BuP) | 94-26-8 | C11H14O3 | 194.23 | 68–69 b 68.5 c | 300.3 c | 159 a 207 c 150 d | 8.37 a, b, d | 3.57 a,c 3.24 d |
Benzylparaben (BeP) | 94-18-8 | C14H12O3 | 228.24 | 110 c | 170 | 107.80 a 160 c 50 d | 8.18 a 8.50 c | 3.56 a 3.27 c |
Pentylparaben (PeP) | 6521-29-5 | C12H16O3 | 208.25 | n.a | n.a | 62.50 a | 8.50 a | 3.96 a |
Phenylparaben (PhP) | 17696-62-7 | C13H10O3 | 214.21 | n.a | n.a | 253 a | 8.40 a | 3.21 a |
Type of Product | Description of Product | Reference |
---|---|---|
Food | Vegetable, Fats, Oils, Sugar extracts, Coffee extracts, Bottled water, Beer, Formula Milk, Yogurts, Wheat flour, Bread, Cakes, Ham, Sausages, Apples, Pears, Cabbages, | [7] |
Food | Soft Drinks, Frozen dairy products, Jams, Jellies, Pickles, Sauces, Desserts, Processed Fish, Flavoring Syrups | [16] |
Cosmetics and Personal Care Products | Shampoos, Conditioners, Shower gels, Scrubs, Sunscreen, Deodorants, Moisturizers | [16] |
Pharmaceuticals | Pills, Syrups, Suppositories, Anesthetics, Eyewashes, Weight-gain drinks, Injectable Solutions, Contraceptives | [22] |
Cosmetics and Personal Care Products | Face, body and hand creams, Eye makeup products, Other makeup products, Night cream and lotions, Mud packs, skin lighteners, Sachets | [21] |
Food | Cloudberry, Yellow passion fruit juice, White wine, Botrytised wine, Bourbon vanilla, Piecrusts, Icings, Toppings, Pastries, Fillings, Olives | [19] |
Food | Beverages, Dairy products, Fats and Oils, Fish and Shellfish, Grains, Meat, Fruits, Vegetables, Cereals, Eggs, Bean products, Cookies/snacks, Condiments | [23,24] |
Personal Care Products | Body wash, Shampoo, Hair conditioner, Face cleanser, Shaving gel, Skin lotion, Hair care products, Perfume, Skin toner, Deodorant, Creams, Sunscreen, Lipstick, Nail polish, Baby diaper cream, Baby powder, Baby lotion and oil, Baby sunscreen | [25] |
Others | Cigarettes, Varnishes, Glue, Animal feed | [17] |
Parabens(s) | Organism | Results | Reference |
---|---|---|---|
MP PP | Rabbit Dog | For dogs, the lethal dose (LD100) was about 4000 mg/kg of PP and for rabbits this was 6000 mg/kg of PP. Regarding MP, the values were 3000 mg/kg for both. Toxicity decreased as the alkyl chain increased. | [21,22,102] |
MP PP | Mouse | Orally, the LD50 was higher than 8000 and 2000 mg/kg for MP and its sodium salt, and above this dose some paralysis can appear in mice. For propylparaben and its sodium salt, the LD50 was higher than 8000 mg/kg and higher than 3700 mg/kg by oral administration, respectively. Recovery occurred quickly from nonfatal doses of MP or PP and their salts. The LD50 values for MP and its sodium salt by intraperitoneal administration were 960 and 760 mg/kg, respectively, and about 170 mg/kg for its salt by intravenous injection. The intraperitoneal LD50 values were 640 and 490 mg/kg for PP and its salt, respectively. A reversible degree of paralysis was observed for an intraperitoneal injection of 400 mg/kg of PP. The sodium salt of PP showed an LD50 of 180 mg/kg, and the intravenous injection of this salt led to paralysis for 50 mg/kg. Fatal dose of MP and its sodium salt produces ataxia, deep depression of nervous system and quick death. The authors suggest that the decrease in toxicity as the alkyl chain increases must be related to a longer hydrolyzation time. | [19,21,22,103] |
PP | Mouse | The LD50 was 6322 mg/kg. Fatal dose of paraben or its salt caused a quick loss of muscular control (ataxia), deep depression of the central nervous system and quick death. | [22,86] |
MP PP | Rat | The LD50 subcutaneous dose was 1200 mg/kg for MP and 1650 mg/kg for PP. | [21,22,104] |
MP PP | Rat | The oral dose was 8000 mg/kg and the intraperitoneal dose was 640 mg/kg for PP and for MP doses 8000 and 960 mg/kg, respectively. | [21,22,38] |
MP | Mouse | MP in 0.85% saline was administrated orally using doses of 100–5000 mg/kg. The acute toxicity of LD50 was estimated to be 2100 mg/kg, since all the mice ingesting a dose of 5000 mg/kg died after 24 h. Some reddened gastric mucosa and congested lungs were observed. For MP in a saline suspension of 21.8% at a dose of 5000 mg/kg, no toxic effect was observed, and this LD50 was estimated to be higher than 5000 mg/kg. For saline suspension of 37–79%, doses of 2600–5600 mg/kg were administrated, and no toxic effects occurred, concluding in an LD50 superior to 5600 mg/kg. | [21,105] |
MP | Fish | The LC50 Zebrafish embryo-larvae for MP was 428 µM (0.065 mg/L) in 96 h postfertilization. | [98] |
Local | Detection Source | Influent Range of Concentration/[ng/L] | Effluent Range of Concentration/[ng/L] | Reference |
---|---|---|---|---|
Santiago de Compostela, Galicia, Spain | LC/ESI-MS/MS | MP: 1926–5138 EP: 452–549 i-PP: <0.38–4.6 n-PP: 1147–1302 i-BuP: 83.6–89.1 n-BuP: 150–181 BeP: <0.2 | MP: <1.11–1.5 EP: <0.34 i-PP: <0.38 n-PP: <0.28 i-BuP: <0.12 n-BuP: <0.21–3.6 BeP: <0.2 | [135] a |
Santiago de Compostela, Galicia, Spain | NACE-DAD NACE-DAD-LVSS | MP: 524–3259 EP: 187–202 PP: 756–904 BeP: 0–655 | MP: <30–112 EP: 0.0–30 PP: 0.0–44 BuP: <25–83 BeP: 0.0–90 | [137] b |
Valencia, Spain | LC/MS | MP: 334 EP:72 PP: 163 BuP: 15 | MP: 11 | [133] c |
Leipzig, Germany | GC/MS | MP: <6.17 iPP: <2.14 nPP: 502 BuP: <3.55 BeP: <9.35 | MP: <6.17 iPP: <2.14 nPP: <13.74 BuP: <3.55 BeP: <9.35 | [138] c |
Spain | LC/MS | MP: 9.0–157 EP: 14–814 PP: 16–913 | MP: 0–40 EP: 0–6.8 PP: 0–24 BeP: 0–1.7 | [76] |
South Wales, United Kingdom | UPLC/MS | MP: 661–15,646 EP: 192–1918 PP: <2–1703 BuP: <2–114 | MP: <3–155 EP: <0.6–69 PP: <1–95 BuP: <1 | [139] |
South Wales, United Kingdom | UPLC/MS | MP: 4550–30,688 EP: 715–3312 PP: 820–8286 BuP: 274–1595 | MP: <3–36 EP: <0.6–43 PP: <1–84 BuP: <1–2 | [139] |
Harbin, China | HPLC/MS-MS | MP: 968–1310 EP: 133–362 PP: 364–496 BuP: 29.3–7.00 BeP: 6.09–2.32 | MP: 57.6–18.2 EP: 1.90–0.94 PP: 8.11–0.37 BuP: 0.01–0.16 BeP: 0–2.63 | [140] d |
Copenhagen, Denmark | LC/MS | MP: 16,322–17,462 EP: 9193–10,519 PP: 12,105–18,631 BuP: 4483–5641 BeP: 12.4–13.5 | MP: <2.8–262 EP: <1.9–290 PP: 49.9–231 BuP: 4.6–550 BeP: <1.2 | [141] d |
Albany, New York, USA | HPLC/MS | MP: 36.8–97.9 EP: 2.74–4.00 PP: 12.9–20.9 BuP: 5.8–7.25 BeP: 0.07 | MP: 0.14 EP: 0.14–0.3 PP: 0.51–1.16 BuP: 0.14–0.61 BeP: 0.07 | [140,142] e |
India | HPLC/ESI-MS | MP: 38.2–267 EP: 4.1–68.1 PP: 38.2–583 BuP: 4.1–10.5 BeP: 0–8.2 | MP: 4.4–41 EP: 1.9–9.8 PP: 2.8–19.3 BuP: 0–2.9 BeP: 0–2.9 | [140,143] d |
Local | Source | Detection Source | Range of Concentration/[ng/L] | Reference |
---|---|---|---|---|
Beijing, China | Pool Water | HPLC/MS | MP: 0.16–872 EP: 0–110 PP: 0–266 BuP: 0–49.2 BeP: 0–6.52 HeP: 0–0.06 | [134] |
Taff River, South Wales, United Kingdom | Surface Water—River | UPLC/MS | MP: <0.3–150 EP: <0.5–12 PP: <0.2–11 BuP: <0.3 | [130] |
Ely River, South Wales, United Kingdom | Surface Water—River | UPLC/MS | MP: <0.3–400 EP: <0.5–15 PP: <0.2–24 BuP: <0.3–52 | [130] |
Taff River, South Wales, United Kingdom | Surface Water—River | UPLC/MS | MP: <0.3–150 EP: <0.5–12 PP: <0.2–11 BuP: <0.3 | [139] |
Ely River, South Wales, United Kingdom | Surface Water—River | UPLC/MS | MP: <0.3–305 EP: <0.5–15 PP: <0.2–22 BuP: <0.3–16 | [139] |
Beijing, China | Surface Water—River | HPLC/MS | MP: 0.81–920 EP: 0–294 PP: 0–565 BuP: 0–41.5 BeP: 0–3.93 HeP: 0–2.94 | [1] |
Santiago de Compostela, Galicia, Spain | Surface Water—River | LC/ESI-MS/MS | MP: 1.8–17.3 EP: 0.13–3.0 BeP: <0.08 i-PP: <0.15 n-PP: <0.11–69 i-BuP: <0.05–4.6 n-BuP: <0.08–7.0 | [135] a |
Glatt River, Switzerland | Surface Water—River | LC/MS | MP: 3.1–17 EP: <0.3–1.6 PP: <0.5–5.8 BuP: <0.2–2.8 BeP: <0.2–4.4 | [144] |
Shizuoka City, Pacific Center Region, Japan | Surface Water | GC/MS | MP: 0–5.4 EP: 0–<4.3 PP: 0–25 BuP: 0–12 | [145] |
Kaveri, Tamiraparani and Vellar River, South India | Surface Water—River | GC/MS | MP: 0.0–22.8 EP: 2.47–147 PP: 0.0–57 | [146] |
Great Pittsburgh, USA | Surface Water | HPLC/MS | MP: 2.2–17.3 PP: 0–12.0 BuP: 0–0.2 | [76] a |
Águeda and Vouga River, Portugal | Surface Water—River | HPLC/MS | MP: <1.6–45 EP: <0.3–2.2 PP: <0.5–6.2 BuP: <0.2–0.8 BeP: <0.2 | [132] |
Caster and Antuã River, Portugal | Surface Water—River | HPLC/MS | MP: 3.3–16 EP: <0.3–6.4 PP: <0.5–64 BuP: <0.2–42 BeP: <0.2–0.3 | [132] |
Marine Coast of Aveiro, Portugal | Surface Water—Sea Water | HPLC/MS | MP: 5.1–21 EP: <0.3–1.6 PP: <0.5–1.6 BuP: <0.2–0.7 BeP: <0.2 | [132] |
Marine Coast of Aveiro, Portugal | Surface Water—Seaport Water | HPLC/MS | MP: 6–24 EP: <0.3–5.3 PP: <0.5–5.3 BuP: <0.2 BeP: <0.2 | [132] |
City of Aveiro, Portugal | Surface Water—Canal Water | HPLC/MS | MP: 5.9–28 EP: <0.3–3.2 PP: <0.5–11 BuP: <0.2–5.9 BeP: <0.2 | [132] |
Lagoon in Aveiro, Portugal | Surface Water—Lagoon | HPLC/MS | MP: 2.1–51 EP: <0.3–6.7 PP: <0.5–7.9 BuP: <0.2–0.2 BeP: <0.2–0.3 | [132] |
Galicia, Spain | Tap Water | NACE-DAD NACE-DAD-LVSS | MP: 40 PP: <25 | [137] a |
Galicia, Spain | Surface Water—River | NACE-DAD NACE-DAD-LVSS | MP: <30–37 EP: 0–<30 PP: 0–<25 BuP: 0–<25 BeP: 0–<31 | [137] a |
Túria River, Spain | Surface Water—River | LC/MS | MP: 119 EP: 16 PP: 145 BuP: 14 | [133] b |
Spain | Tap Water | LC/MS | MP: 12 PP: 9 BuP: 28 | [133] b |
Spain | Bottled Water | LC/MS | MP: 40 EP: 2 PP: 23 BuP: 36 | [133] b |
Leipzig, Germany | Tap Water | GC/MS | MP: 17 iPP: <2.14 nPP: <13.74 BuP: <3.55 BeP: <9.35 | [138] b |
Rio Grande, Brazil | Bottled Water | LC/MS | MP: 90–242 | [18] |
Tokushima, Japan | Surface Water—River | LC/MS | MP: 49–676 EP: 2.8–64 n-PP: 7.5–207 i-PP: <1.6–46 n-BuP: 10–163 i-BuP: 1.4–13 BeP: <0.2–2.3 | [101] c |
Osaka, Japan | Surface Water—River | LC/MS | MP: 25–199 EP: <1.3–12 n-PP: <0.8–20 i-PP: <1.6 n-BuP: <0.6–2.6 i-BuP: <1.2 BeP: <0.2 | [101] c |
Ebro River, Spain | Surface Water—River | LC/MS | MP: 1.4–27 EP: 0–13 PP: 0.5–15 BeP: 0–1.1 | [76] |
Pearl River, Guangzhou, China | Surface Water—River | GC/MS | MP: <0.5–1062 PP: 5–3142 | [75] |
Wielkopolska Voivodeship, Poland | Surface Water—River and Lake | LC/MS | MP: 1.7–1598 EP: 0.8–27.5 PP: 0.5–93.9 BuP: 0.6–22.6 BeP: 0–31.0 | [147] |
Poland | Surface Water—River and Lake | HPLC/MS | MP: 8.7–465.6 PP: 0–144.4 BuP: 0–19.6 BeP: 0–8.6 | [148] |
Mogi Guaçu River, São Paulo, Brazil | Surface Water—River | LC | MP: 0–27,500 EP: <800–30,500 PP: <500–52,100 BuP: <800–19,900 | [147,149] a |
Parabens(s) | Administration Route | Results | Reference |
---|---|---|---|
PP | Oral (2 g) | 17.4%, 13.7%, 3.7% and 55% were excreted as p-hydroxybenzoic acid, free glycine and pair glycine and paired with sulfuric acid, respectively. PP was not found in urine. | [22,35] |
PP | Oral (10 or 20 mg/kg) | After 60 min, 135 min and 255 min, the paraben was detected in human serum at a maximum of 4.5 µg/mL, but the ester was not detected. | [22,157] |
MP EP PP BuP Iso-BuP | (unknown exact administration source) | It was measured the concentration of paraben esters in human breast tumor. The mean concentration found was 12.7, 2.0, 2.6, 2.3 and 0.9 ng/g for MP, EP, PP, BuP and iso-BuP, respectively. The authors suggest this could be due to some paraben being adsorbed and retained in body tissue without being hydrolyzed. | [28] |
Parabens(s) | Animal | Administration Route | Results | Reference |
---|---|---|---|---|
MP EP PP BuP | Dogs | Intravenous (50 mg/kg) Oral (1 g/kg) | Blood and urine analyzed. Very low quantity remained in the blood after administration, but p-hydroxybenzoic acid was detected in blood. In 100 mg/kg of MP and PP administered intravenously, the ester was only detected in brain, spleen, and pancreas, but high concentrations of metabolites were detected in kidneys and liver. By oral administration of 1 g/kg/day for 1 year, the existence of accumulation of MP or PP was not verified, and 66% and 96% of these doses of MP and PP, respectively, were excreted daily in urine. Of the 66% of MP excreted, 21% was as p-hydroxybenzoic acid and 33% was as glucuronic acid conjugates. The recovery of all parabens was between 58% and 94%, except for BuP which was 40–48%. | [19,21,22,164] |
MP EP PP BuP | Rabbits | Oral (0.4 or 0.8 g/kg) | 39% of MP was excreted as p-hydroxybenzoic acid, 15% as glycine, 7% and 15% as glucuronic acid ester and ether, and 10% as sulfuric acid. 30% of the dose of propylparaben was excreted as p-hydroxybenzoic acid, 24% as glycine, 7% and 13% as glucuronic acid ester and ether, and 7% as sulfuric acid. The excretion rate of 0.8 g/kg was quicker than 0.4 g/kg, and about 70% of 0.4 g/kg was excreted in 9 h, 86% in 24 h and 88% in 48 h. Oral administration of parabens resulted in excretion of 0.2–0.9% of the unchanged ester by 24 h. As the length of the alkyl chain increased, the rate of urinary excretion decreased, so, in general, after 24 h, 25–39% was excreted as p-hydroxybenzoic acid, 25–29% as the glycine conjugate, 5–8% and 10–18% as ester and ether glucuronide, respectively, and 7–12% as sulfate. | [19,21,22,165,166,167] |
MP EP PP | Rats | Oral (100 mg) | Quick absorption by gastrointestinal tract and easy hydrolyzation into p-hydroxybenzoic acid in different organs. 30 min after administration, paraben metabolites were detected in urine, and 90 min after the maximum excretion of the metabolites was observed. P-hydroxyhippuric acid was detected in urine after 30 min with an increase in concentration for the next 4 h. After 90 min, about 67–75% of the total paraben dose was excreted as p-hydroxybenzoic acid, and 8–9% as glucuronyl derivatives. The concentration of parabens or benzoic acid in blood was extremely low. | [19,21,22,168] |
EP PP | Cats | Oral (158 mg/kg) | For urine, at 24 and 72 h, about 90% and 95.6% of the dose was excreted, respectively, and 6% and 3% in feces at 24 h, for EP and PP, respectively. The two major metabolites were p-hydroxyhippuric acid and p-hydroxybenzoic acid. After 72 h post oral administration, the PP was completely excreted. | [19,22,169] |
PP Other parabens | Frogs | Dermal absorption | Paraben adsorption was higher for longer chain and fastest during the first 20 min. | [22,170] |
MP PP | Rats | Oral | For 1 g/kg/day of MP and PP in 1 year, about 96–100% was excreted daily. | [21,102] |
MP PP | Rabbits Cats Dogs | Oral | The administration of MP and PP led to an excretion in urine of 15–40% and 4–21%, respectively, as p-hydroxybenzoic acid. MP and PP were not detected in feces, what suggests full absorption of the parabens. | [21,171] |
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Lincho, J.; Martins, R.C.; Gomes, J. Paraben Compounds—Part I: An Overview of Their Characteristics, Detection, and Impacts. Appl. Sci. 2021, 11, 2307. https://doi.org/10.3390/app11052307
Lincho J, Martins RC, Gomes J. Paraben Compounds—Part I: An Overview of Their Characteristics, Detection, and Impacts. Applied Sciences. 2021; 11(5):2307. https://doi.org/10.3390/app11052307
Chicago/Turabian StyleLincho, João, Rui C. Martins, and João Gomes. 2021. "Paraben Compounds—Part I: An Overview of Their Characteristics, Detection, and Impacts" Applied Sciences 11, no. 5: 2307. https://doi.org/10.3390/app11052307
APA StyleLincho, J., Martins, R. C., & Gomes, J. (2021). Paraben Compounds—Part I: An Overview of Their Characteristics, Detection, and Impacts. Applied Sciences, 11(5), 2307. https://doi.org/10.3390/app11052307