Probabilistic ecological hazard assessment of parabens using Daphnia magna and Pimephales promelas

Parabens are common antimicrobial agents found in thousands of pharmaceuticals and personal care products. Parabens are introduced into aquatic ecosystems from wastewater treatment plant effluents and have been detected in surface waters in the low microgram per liter range. Although these compounds display low toxicity in mammals, paraben toxicity to aquatic organisms has not been investigated. Standardized acute and subchronic endpoints in larval fish (Pimephales promelas) and cladoceran (Daphnia magna) models were examined for seven different parabens (methyl-, ethyl-, isopropyl-, propyl-, isobutyl-, butyl-, benzylparaben), which encompassed a range of log P values. Paraben 48 h median lethal concentration values (LC50) ranged from 4.0 to 24.6 mg/L in D. magna and 3.3 to >160.0 mg/L in fathead minnow. Growth and reproduction in D. magna had lowest-observed-effect concentrations (LOECs) ranging from 0.12 to 9.0 mg/L and 1.5 to 6.0 mg/L, respectively. Fathead minnow growth was adversely affected at levels ranging from 1.0 to 25.0 mg/L. Aquatic toxicity of the parabens was inversely related to lipophilicity, suggesting that responses using standardized endpoints resulted from narcosis. Utilizing toxicity benchmark concentrations (e.g., LC50s, LOECs) for each compound, chemical toxicity distributions, a probabilistic hazard assessment technique, were developed to assess the probabilities of detecting parabens that elicit a response at or below a given concentration. For the responses assessed in the present study, the 5th centile values (the concentration at which 5% of parabens elicit a response) ranged from 15 microg/L to 2.43 mg/L, with D. magna growth eliciting the lowest 5th centile value and acute D. magna mortality eliciting the highest. The distributions demonstrated that at environmentally relevant concentrations in developed countries there is limited acute or subchronic aquatic hazard of parabens to the organisms and responses examined.

[1]  G. S. Pope,et al.  Oestrogenic activity of benzylparaben , 2003, Journal of applied toxicology : JAT.

[2]  J Ashby,et al.  Some alkyl hydroxy benzoate preservatives (parabens) are estrogenic. , 1998, Toxicology and applied pharmacology.

[3]  T. Angelov,et al.  HPLC Determination of pKa of Parabens and Investigation on their Lipophilicity Parameters , 2007 .

[4]  M. Soni,et al.  Safety assessment of esters of p-hydroxybenzoic acid (parabens). , 2005, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[5]  T. Eklund,et al.  Inhibition of growth and uptake processes in bacteria by some chemical food preservatives. , 1980, The Journal of applied bacteriology.

[6]  H. Sandermann Ecotoxicology of narcosis: stereoselectivity and potential target sites. , 2008, Chemosphere.

[7]  G. S. Pope,et al.  Oestrogenic activity of isobutylparaben in vitro and in vivo , 2002, Journal of applied toxicology : JAT.

[8]  A. V. van Wezel,et al.  Narcosis due to environmental pollutants in aquatic organisms: residue-based toxicity, mechanisms, and membrane burdens. , 1995, Critical reviews in toxicology.

[9]  Carina Carlsson,et al.  Are pharmaceuticals potent environmental pollutants? Part II: environmental risk assessments of selected pharmaceutical excipients. , 2006, The Science of the total environment.

[10]  S. Tsuboi,et al.  Growth Stimulation and Inhibition Effects of 4-Hydroxybenzoic Acid and Some Related Compounds on the Freshwater Green Alga Pseudokirchneriella subcapitata , 2006, Archives of environmental contamination and toxicology.

[11]  W. Lambert,et al.  Analysis of multiple endocrine disruptors in environmental waters via wide-spectrum solid-phase extraction and dual-polarity ionization LC-ion trap-MS/MS. , 2004, Analytical chemistry.

[12]  C. N. Huhtanen,et al.  Inhibition of Clostridium botulinum by p-Hydroxybenzoic Acid n-Alkyl Esters , 1979, Antimicrobial Agents and Chemotherapy.

[13]  C. Russom,et al.  Predicting modes of toxic action from chemical structure: Acute toxicity in the fathead minnow (Pimephales promelas) , 1997 .

[14]  Barbara Kasprzyk-Hordern,et al.  The occurrence of pharmaceuticals, personal care products, endocrine disruptors and illicit drugs in surface water in South Wales, UK. , 2008, Water research.

[15]  R. Brain,et al.  Comparison of the sensitivities of common in vitro and in vivo assays of estrogenic activity: Application of chemical toxicity distributions , 2008, Environmental toxicology and chemistry.

[16]  R. Brain,et al.  Probabilistic ecological hazard assessment: evaluating pharmaceutical effects on aquatic higher plants as an example. , 2006, Ecotoxicology and environmental safety.

[17]  D. Orvos,et al.  Aquatic toxicity of triclosan , 2002, Environmental toxicology and chemistry.

[18]  Katsutada Takahashi,et al.  Calorimetric Analysis of Antimicrobial Effect of p-Hydroxybenzoic Acid Alkyl Esters , 1999 .

[19]  D. Burmaster,et al.  Using lognormal distributions and lognormal probability plots in probabilistic risk assessments , 1997 .

[20]  W. Waller,et al.  Assessment of Toxicity Reduction in Wastewater Effluent Flowing Through a Treatment Wetland Using Pimephales promelas, Ceriodaphnia dubia, and Vibrio fischeri , 2002, Archives of environmental contamination and toxicology.

[21]  W. Waller,et al.  Influence of the addition of cerophyl® on the Selenastrum capricornutum diet of the cladoceran Ceriodaphnia dubia , 1992 .

[22]  Kyungho Choi,et al.  Aquatic toxicity of acetaminophen, carbamazepine, cimetidine, diltiazem and six major sulfonamides, and their potential ecological risks in Korea. , 2007, Environment international.

[23]  Bryan W Brooks,et al.  Daphnia magna responses to a vertebrate estrogen receptor agonist and an antagonist: a multigenerational study. , 2007, Ecotoxicology and environmental safety.

[24]  G. S. Pope,et al.  Concentrations of parabens in human breast tumours , 2004, Journal of applied toxicology : JAT.

[25]  B. Brooks,et al.  Water Quality of Effluent-dominated Ecosystems: Ecotoxicological, Hydrological, and Management Considerations , 2006, Hydrobiologia.

[26]  H. Inui,et al.  Effect of UV screens and preservatives on vitellogenin and choriogenin production in male medaka (Oryzias latipes). , 2003, Toxicology.

[27]  Alejandro J. Ramirez,et al.  Enantiospecific toxicity of the β‐blocker propranolol to Daphnia magna and Pimephales promelas , 2006, Environmental toxicology and chemistry.

[28]  G. S. Pope,et al.  Oestrogenic activity of parabens in MCF7 human breast cancer cells , 2002, The Journal of Steroid Biochemistry and Molecular Biology.

[29]  M. Lavorgna,et al.  Toxic and genotoxic evaluation of six antibiotics on non-target organisms. , 2005, The Science of the total environment.

[30]  C. Erratico,et al.  Vitellogenin as a biomarker for estrogenic effects in brown trout, Salmo trutta: Laboratory and field investigations , 2008, Environmental toxicology and chemistry.

[31]  B. Brooks,et al.  Physiological and Reproductive Effects of Beta Adrenergic Receptor Antagonists in Daphnia magna , 2006, Archives of environmental contamination and toxicology.

[32]  B. Halling‐Sørensen,et al.  Acute and chronic toxicity of veterinary antibiotics to Daphnia magna. , 2000, Chemosphere.

[33]  Paul D. Jones,et al.  Probabilistic risk assessment of agrochemicals in the environment , 2000 .

[34]  N. Kruijf,et al.  Contents of methyl‐, ethyl‐, propyl‐, butyl‐ and benzylparaben in cosmetic products , 1995, Contact dermatitis.

[35]  Hing-Biu Lee,et al.  Determination of endocrine-disrupting phenols, acidic pharmaceuticals, and personal-care products in sewage by solid-phase extraction and gas chromatography-mass spectrometry. , 2005, Journal of chromatography. A.

[36]  D. Larsson,et al.  Effluent from drug manufactures contains extremely high levels of pharmaceuticals. , 2007, Journal of hazardous materials.

[37]  N. Negreira,et al.  Formation of halogenated by-products of parabens in chlorinated water. , 2006, Analytica chimica acta.

[38]  I. Kano,et al.  ER-dependent estrogenic activity of parabens assessed by proliferation of human breast cancer MCF-7 cells and expression of ERalpha and PR. , 2001, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.