In Vivo Estrogenicity of Nonylphenol and Its Ethoxylates in the Canadian Environment

The relative estrogenicity of nonylphenol and its ethoxylates has not been clearly demonstrated in the literature, despite the importance of this information for interpreting the environmental risk of these chemicals. There appears to be a discrepancy between the relative acute/chronic toxicity and estrogenicity reported in previous studies. These studies have suggested that the relatively higher concentrations of nonylphenol polyethoxylate metabolites (NP_nEO, NP_nEC) in municipal effluents may represent a risk to the environment. However, there is considerable uncertainty associated with the estimates of relative estrogenicity of these metabolites.

Plasma vitellogenin (Vg) was measured in rainbow trout (Oncorhynchus mykiss) after a 21-d flow-through exposure to concentrations of 1–250 μ g · L^{? 1} nonylphenol (NP), 1–280 μ g · L^{? 1} nonylphenol 1-ethoxylate (NP1EO), or 24–1450 μ g · L^{? 1} nonylphenol 1-ethoxycarboxylate (NP1EC). All three chemicals induced plasma Vg to varying degrees, their relative estrogenicity being NP > NP1EO > > NP1EC. Measurements of the relative potency of NP1EO and NP1EC compared to NP, yielded ratios of 0.22 and 0.03, respectively. These values are in general agreement with relative acute and chronic toxicity data in the literature. A re-evaluation of the estrogenicity of the biodegradation products of nonylphenol polyethoxylates in Canadian sewage treatment plant effluents was performed, using the relative estrogenicity determined in this study, and revealed that the contribution of alkylphenol polyethoxylates to effluent estrogenicity is significant but less than previously estimated. The ability of these chemicals, however, to act in concert with other estrogenic compounds such as 17β -estradiol, estrone, and 17α -ethinylestradiol, to provide a cumulative estrogenic exposure for the biota needs to be investigated.     

A Hazard Assessment of Aggregate Exposure to Nonylphenol and Nonylphenol Mono- and Di-ethoxylates in the Aquatic Environment

The most commonly detected environmental metabolites of nonylphenol ethoxylates (NPE) are nonylphenol monoethoxylate (NPE1), nonylphenol diethoxylate (NPE2), nonylphenol ether carboxylates (NPEC), and nonylphenol (NP). Since NPEC have relatively low toxicity, the most relevant NPE metabolites for conducting an aggregate hazard assessment are NP, NPE1, and NPE2. Recent studies support the validity of the U.S. Environmental Protection Agency (2005) chronic water quality criteria (WQC) for NP in freshwater and saltwater environments; thus, these criteria were used as reference values in the aggregate hazard assessment. The toxic equivalency approach was used to assess the aggregate hazard of NP, NPE1, and NPE2. A review of relevant studies indicated that the toxic equivalency factor (TEF) for NPE1 and NPE2 approximated 0.37, which supported the use of the more conservative TEF value of 0.50 used by Environment Canada (2001) for NPE1 and NPE2. The interaction of toxicities between NP, NPE1, and NPE2 is assumed to be additive based on a review of the current literature and the shared mechanism of action of these compounds. The data support previous findings that there is a low likelihood that aggregate NP-equivalent concentrations of NPE and its metabolites in U.S. waters will exceed the national chronic WQC for NP.     

Human Risk Assessment for Nonylphenol

This article presents a risk assessment for human exposure to nonylphenol (NP). We critically reviewed and assessed all relevant full-text publications based on a variety of data quality attributes. Two categories of data, environmental monitoring and biomonitoring from exposed individuals, were used to estimate human exposure to NP. Environmental monitoring data included the measurement of NP in food, water, air, and dust. From these data and estimates of human intake rates for the sources, exposures were estimated from each source and source-specific Margins of Exposure (MOEs) calculated. However, the nature of the populations studied prevented the calculation of aggregate exposure calculations from these data. Rather, the most reliable estimates of aggregate exposure to NP were those derived from biomonitoring studies in exposed individuals. Using the daily absorbed dose estimates for NP, MOEs were calculated for these populations. The MOEs were based on the use of a No-Observed-Adverse-Effect-Level (NOAEL) for sensitive toxicological endpoints of interest, that is, systemic and reproductive toxicity from continuous-feeding more than 3.5 generations (13 mg/kg/day). The MOEs were all greater than 1000 (ranging from 2863 to 8.4 × 10⁷), clearly indicating reasonable certainty of no harm for source-specific and aggregate (based on biomonitoring) exposures to NP.     

Alteration of the Enantioselective Toxicity of Diclofop Acid by Nonylphenol: Effect on Ascorbate‐Glutathione Cycle in Microcystis Aeruginosa

The enantioselective effects of chiral compounds have been the subject of extensive studies in recent years due to their important implications for contaminant behavior and risk as well as the design of drug and pesticide formulations. The potential alterations of enantioselectivity, however, still remain elusive from the available data suggesting the effects of numerous environmental factors and the coexisting achiral and chiral compounds. Herein we studied the effect of nonylphenol (NP), a ubiquitous contaminant and ingredient in pesticide formulation, on the enantioselectivity of diclofop acid (DC) through ascorbate‐glutathione (AsA‐GSH) cycle in Microcystis aeruginosa. The enantioselectivity of DC in the AsA and GSH antioxidant defense system of M. aeruginosa was affected significantly by the addition of NP. Specifically, although R‐ DC and S‐DC were added with an equal toxic concentration (at their EC₅₀ values), NP addition to the DC treatments altered the enantiomeric ratios of the activities of monodehydroascorbate reductase (MDHAR) and glutathione reductase (GR), key enzymes in the regeneration of AsA and GSH, respectively. NP also modified the enantiomeric ratios of AsA and GSH levels in both the AsA and GSH antioxidant defense systems of M. aeruginosa. Overall, the oxidative damage induced by R‐DC was further deteriorated, whereas that induced by S‐DC was alleviated after NP addition. These altered enantioselectivities indicate a need to reexamine the risks and biological effects of chiral compounds in the complex environmental matrices containing a multitude of other chemicals, including commercial chiral agricultural chemicals. Chirality 28:475–481, 2016. © 2016 Wiley Periodicals, Inc.     

Predicting the Effects of Endocrine Disrupting Chemicals on Fish Populations

This study evaluates the applicability and sensitivity of fish population dynamics modeling in assessing the potential effects of individual chemicals on population sustainability and recovery. Fish reproductive health is an increasingly important issue for ecological risk assessment following international concern over endocrine disruption. Life-history data from natural brook trout and fathead minnow populations were combined with effects data from laboratory-based studies, mainly concerning species other than brook trout and fathead minnows, to assess the likely impact of nonylphenol (NP) and methoxychlor (MXC) on brook trout (Salvelinus fontinalis) and fathead minnow (Pimephales promelas) population size. A delay differential equation (DDE) model with a 1-day timestep was used to predict the population dynamics of the brook trout and fathead minnows. The model predicts that NP, could enhance populations by up to 17% at a concentration of 30?µg l^?1 based on the results of reduction in survival and increased fecundity from life-cycle toxicity tests, however attempting to allow for growth reduction and its effect on fecundity results in a prediction of a 28% reduction in population numbers. For fathead minnows the DDE model predicts that the same concentration of NP could cause a population reduction of 21%. The differences in these predictions are related to these two species having different life history strategies, which are considered in the parameterization of the model. Post-application concentrations of MXC may peak around 300?µg l^?1 and then decline rapidly with time. Predictions show that such applications could cause a reduction of up to 30% in brook trout populations if the application occurs at the peak of the spawning season on successive years but that the effect would be less than 1% if the spawning season is avoided. Effects on the fathead minnow population size are predicted to be smaller (<4%) even if application occurs during the spawning period. Risk based statistics generated by the population dynamics models, such as interval decline risk or quasiextinction risk and predicted time to recovery complement traditional effects parameters such as LC50 and LOEC and may ultimately prove to be more useful in risk assessment.     

Toxic effect of gestational exposure to nonylphenol on F1 male rats

OBJECTIVE: The purpose of this study was to examine whether gestational exposure to major environmental endocrine‐disrupting chemicals, nonylphenol (NP), would lead to nerve behavioral and learning and memory capacity alterations in the male offspring of rats, and reproductive development alterations in the male offspring of rats. METHODS: Dams were gavaged with NP at a dose level of 50 mg/kg/day, 100 mg/kg/day or 200 mg/kg/day daily from gestational day 9 to 15, and at a dose level of 40 mg/kg/day, 80 mg/kg/day or 200 mg/kg/day daily from gestational day 14 to 19 (transplacental exposures). RESULTS: Exposure to 200 mg/kg/day NP produced a significant decrease in learning and memory functions in offspring rats (P<0.05) in Morris water maze task, as demonstrated by the increased escape latency and number of error. In Step‐down Avoidance Test, offspring rats exposed to NP spent more reaction time (RT) and presented lower latency to first step‐down than the control offspring (P<0.01). In utero exposure to 80 and 200 mg/kg/day NP produced a significant decrease in the number of live pups per litter and ratio of anogenital distance to body length on PND 0 (P<0.05), and also testes and prostate weight, activities of ALP, plasma testosterone concentration, cauda epididymis sperm counts, daily sperm production et al. respectively on PND 90 (P<0.05). Histopathological examination of the brain biopsy illustrates that exposure to NP at high dose induces the presence of abnormal distribution of spermatozoa showed in lumina of the seminiferous tubules, and absence of spermatogenesis and spermiogenesis. CONCLUSION: Gestational exposure to nonylphenol might induce neurotoxic and reproductive toxic effects on F1 male rats. Birth Defects Res (Part B) 89:418–428, 2010. © 2010 Wiley‐Liss, Inc.     

Nonylphenol exposure is associated with oxidative and nitrative stress in pregnant women

ABSTRACT

Animal studies have shown that exposure to nonylphenol (NP) increases oxidative/nitrative stress, but whether it does so in humans is unknown. This study examines prenatal exposure to NP and its effects on oxidatively/nitratively damaged DNA, lipid peroxidation, and the activities of antioxidants. A total of 146 urine and blood specimens were collected during gestational weeks 27–38 and hospital admission for delivery, respectively. Urinary NP was analyzed by high-performance liquid chromatography (HPLC). Urinary biomarkers of oxidatively/nitratively damaged DNA and lipid peroxidation, including 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodG), 8-nitroguanine (8-NO₂Gua), 8-iso-prostaglandin F_2α (8-isoPF_2α) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA), were simultaneously analyzed using isotope-dilution liquid-chromatography/electron spray ionization tandem mass spectrometry. The activities of maternal plasma superoxide dismutase and glutathione peroxidase were analyzed by enzyme-linked immunosorbent assay. Urinary NP level was significantly associated with 8-oxodG and 8-NO₂Gua levels in late pregnancy, suggesting that NP may enhance oxidatively and nitratively damaged DNA. The adjusted odds ratios for high 8-oxodG level exhibited a significantly dose–response relationship with NP levels, stratified into four quartiles. 8-oxodG appears to be a more sensitive and effective biomarker of NP exposure than 8-NO₂Gua. These relationships suggest NP may play a role in the pregnancy complications.     

Integrated Human and Ecological Risk Assessment: A Case Study of Organophosphorous Pesticides in the Environment

This study was chosen as an example of integrated risk assessment because organophosphorous esters (OPs) share exposure characteristics for different species, including human beings and because a common mechanism of action can be identified. The “Framework for the integration of health and ecological risk assessment” is being tested against a deterministic integrated environmental health risk assessment for OPs used in a typical farming community. It is argued that the integrated approach helps both the risk manager and the risk assessor in formulating a more holistic approach toward the risk of the use of OP-esters. It avoids conclusions based on incomplete assessments or on separate assessments. The database available can be expanded and results can be expressed in a more coherent manner. In the integrated exposure assessment of OPs, the risk assessments for human beings and the environment share many communalities with regards to sources and emissions, distribution routes and exposure scenarios. The site of action of OPs, acetylcholinesterase, has been established in a vast array of species, including humans. It follows that in the integrated approach the effects assessment for various species will show communalities in reported effects and standard setting approaches. In the risk characterization, a common set of evidence, common criteria, and common interpretations of those criteria are used to determine the cause of human and ecological effects that co-occur or are apparently associated with exposure to OPs. Results of health and ecological risk assessments are presented in a common format that facilitates comparison of results. It avoids acceptable risk conclusions with regard to the environment, which are unacceptable with regard to human risk and vice versa. Risk managers will be prompted to a more balanced judgement and understanding and acceptance of risk reduction measures will be facilitated.     

壬基酚对波纹巴非蛤(Paphia undulata)内脏团毒性效应

采用半静态毒性实验方法测定了壬基酚(NP)对波纹巴非蛤(Paphiaundulata)的96-hLC50值,同时研究了低、中、高3个浓度(1、10和25μg·L-1)NP胁迫下以及胁迫解除后波纹巴非蛤内脏团中超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、过氧化物酶(POD)以及丙二醛(MDA)含量的变化趋势。急性毒性实验结果表明,NP对波纹巴非蛤的96-hLC50值为260μg·L-1。胁迫初期,低、中浓度组的SOD活性被极显著抑制(P<0.01),而POD活性则被极显著诱导(P<0.01),表现为典型的"毒性兴奋效应"。胁迫过程中,低、中浓度组波纹巴非蛤内脏团的SOD活性和GSH含量呈先下降后上升的趋势,而POD活性和MDA含量则呈先上升后下降的趋势;高浓度组SOD活性呈先抑制后诱导的趋势,POD活性和MDA含量呈先下降后升高再降低的趋势,而GSH含量则一直显著高于对照组。GSH和MDA含量在整个胁迫期间均出现剧烈的波动,且浓度越高其变化程度越大。胁迫解除后,低、中浓度组的各种指标逐渐恢复到对照组水平,但高浓度组与对照组仍存在着极显著差异。上述结果表明,NP对波纹巴非蛤内脏团的抗氧化酶系统造成较为明显的影响,而波纹巴非蛤则对一定程度的NP胁迫所带来的氧化损伤具有自我修复的能力,但对高浓度NP胁迫所造成的脂质过氧化损伤短期内却无法消除。     

生态风险评价方法述评

生态风险是由环境的自然变化或人类活动引起的生态系统组成、结构的改变而导致系统功能损失的可能性。生态风险评价是定量预测各种风险源对生态系统产生风险的或然性以及评估该风险可接受程度的方法体系,因而是生态环境风险管理与决策的定量依据。在介绍了生态风险概念的基础上,按照风险源性质的分类标准将生态风险划分为化学污染类风险源、生态事件类风险源、复合类风险源3类,并分别论述了3类生态风险对应评价方法的特点与发展的方向。另外,针对生态风险评价研究的现状,讨论了我国生态风险研究的优先领域,包括建立急性、慢性毒理数据库,构建外来生物入侵风险评价标准等,同时,建议将综合概率统计学、复杂系统理论与遥感技术等手段引入生态风险评价方法中,以进一步提高风险评价结果在生态风险管理中的有效性。     

Combined action of X-rays and nonylphenol on mouse sperm

The aim of this study was to assess the effects of 2-weeks’ X-ray and/or nonylphenol (NP) exposure on male mice’s sperm count and quality. Pzh:SFIS mice were exposed to X-rays (0.05 Gy, 0.10 Gy, 0.20 Gy) or to nonylphenol (25 mg/kg bw, 50 mg/kg bw, 100 mg/kg bw) or to both agents (0.05 Gy + 25 mg/kg bw NP, 0.10 Gy + 50 mg/kg bw NP). At 24 h and 5 weeks after the end of exposure the sperm count, morphology and frequency of DNA damage in the male germ cells were estimated. Each agent alone diminished sperm count and morphology. The dose of 0.05 Gy of X-rays decreased the frequency of DNA damage. Combined exposure to lower doses of both agents significantly improved sperm morphology and decreased the level of DNA damage compared to one agent alone. Combined exposure to higher doses reduced the frequency of DNA damage compared to the effect of the appropriate dose of NP. Results of combined exposure to low doses of both agents suggest that 0.05 Gy of X-rays stimulate the DNA damagecontrol system and in consequence repair of DNA caused by X-rays and NP. It may be correlated with increased antioxidant capacity.     

Degradation of the Radioactive and Non-labelled Branched 4(3',5'-dimethyl 3'-heptyl)-phenol Nonylphenol Isomer by Sphingomonas TTNP3

The degradation of the 4(3',5'-dimethyl-3'-heptyl)-phenol (p353NP) nonylphenol isomer in cultures of Sphingomonas TTNP3 supplemented with the technical mixture of nonylphenol was first assessed. Then the radioactive and non-labelled form of these diastereomers were both synthesised. The radioactive isomers were synthesised using [ring-U-14C]-labelled phenol and 3,5-dimethyl-3-heptanol by Friedel and Crafts alkylation. The time-course of degradation was performed with and without 14C-p353NP; balancing of radioactivity was calculated from different soluble fractions (organic, aqueous), bacterial biomass, and 14CO2 evolved as mineralization product. The noticeable portion of 14C bound to biomass showed that at least the aromatic ring of 14C-p353NP was degraded and served as energy source and probably as carbon source for bacterial growth. In addition, the appearance of 3,5-dimethyl-3-heptanol, the nonanol corresponding with the side-chain of p353NP, was demonstrated in the bacterial media, and its concentration determined during the course of fermentation. Besides the parent 14C-p353NP, no other radioactive compounds, i.e. metabolites of 14C-p353NP were detected in the media.     

Contamination of Paddy Soil by Endocrine-Disrupting Chemicals Affects Soil Microbe Abundance and Diversity

We describe the effect on the population of Eubacteria and Archaea species of adding the endocrine-disrupting chemicals (EDCs) nonylphenol (NP) or dibutylphthalate (DBP) to a typical paddy soil. Fluorescence in-situ hybridization was used to discriminate between the two phyla, and denaturing gradient gel electrophoresis (DGGE) of an amplified fragment of the 16S rRNA locus was used to profile the species present. The population of both Eubacteria and Archaea species was reduced by the presence of NP or DBP, and the deleterious effect was greater for the Eubacteria. The DGGE profiles were used to assess the species diversity in the polluted and non-polluted soil samples. This showed that DBP was less damaging than NP₅₀. It was clear that EDCs can significantly affect paddy soil microbial diversity, both with respect to population size and species representation.     

Changes in apoptotic rate and cell viability in three fish epidermis cultures after exposure to nonylphenol and to a wastewater sample containing low concentrations of nonylphenol

Three types of epidermal cultures of fish were used for toxicological investigations, a primary cell culture and a tissue culture prepared from the rainbow trout Oncorhynchus mykiss Walbaum and the cell line EPC, derived from a skin tumour of the carp Cyprinus carpio L. Two studies were carried out to compare the different culture systems. In the first cultures were incubated with nonylphenol and in the second set of experiments the cell cultures were exposed to a wastewater sample containing low concentrations of nonylphenol (NP). Both cell cultures were similarly sensitive to nonylphenol with respect to the endpoints cell viability (LC₅₀ (24 h) 47.1 μM NP (primary cell culture) and 44.2 μM NP (EPC)) values and apoptotic rate (significantly increased apoptotic rate after exposure to 50 μM NP for 24 h, p < 0.001 (primary cell culture), p = 0.008 (EPC)). The explant culture was slightly less sensitive (increased apoptotic rate after exposure to 50 μM NP for 24 h, but not significant: p = 0.385), which could be due to the capabilities of a differentiated tissue, providing more protective repair mechanisms, compared with single cells. All cultures revealed a concentration–response relationship for the endpoint apoptotic rate after the application of nonylphenol for 24 h. After wastewater exposure, a significant decrease in the apoptotic rate was measured in the primary cell culture (dilution wastewater : medium 1:1:p = 0.018; dilution wastewater : medium 1:2:p = 0.003), whereas the cell line EPC did not reveal any effects. Our results show that the endpoint apoptotic rate is more sensitive than the parameter cell viability for detecting adverse effects of a wastewater sample.     

Exposure Analysis of C8- and C9-Alkylphenols,Alkylphenol Ethoxylates,and Their Metabolites in Surface Water Systems within the United States

This study was conducted to develop a statistical understanding of exposures to C8- and C9-alkylphenol ethoxylates (APEO) and their metabolites (APEM) in U.S. surface waters. Concentrations of APEO/APEM (all analytes) in freshwater have been reported by 19 investigations over the past 15 years. Only limited data are available for sediments and marine ecosystems. Based on the frequency of detection in surface waters, 67% of all analytes were below their detection limits. Although maximum reported concentrations varied with time, the average and 90th centile concentrations have remained relatively constant. Examination of frequency distributions for nonylphenol (NP) concentrations indicated that 99% of the levels in fresh surface waters are below the U.S. Environmental Protection Agency's Aquatic Life Ambient Chronic Water Quality Criteria for NP (6.6 μg/L). A conservative evaluation of aggregated NPEO/NPEM concentrations suggested that 97% of the samples contained aggregate NP equivalent concentrations that are also below 6.6 μg/L. These results suggest that on a nationwide basis, the likelihood of surface water concentrations exceeding the chronic USEPA Water Quality Criterion for NP is low.     

A Weight of Evidence Analysis of the Chronic Ecotoxicity of Nonylphenol Ethoxylates,Nonylphenol Ether Carboxylates,and Nonylphenol

Nonylphenol ethoxylates (NPE) are widely used surfactant compounds with many domestic and industrial applications. Due to the nature of their use in down-the-drain applications, spent NPE are discharged to septic systems or to wastewater treatment plants. Biodegradation of parent material during treatment is often incomplete, leading to release of NPE and their degradation intermediates into the environment. Considerable aquatic toxicity research has occurred on NPE and particularly on nonylphenol (NP). Available data were subjected to a quality review and all studies of acceptable quality were used in a weight of evidence hazard assessment. Data for NP were further analyzed using a Species Sensitivities Distribution (SSD) approach. About 90 chronic values are available (ChVs, geometric mean of the no-observed effect concentration and lowest-observed effect concentration for each endpoint reported), which may be reduced to average ChVs for each tested species. Higher mole NPE (NPE ≥ 9) had ChVs ranging from 900 to 14,100 μg/L, ChVs for the low mole nonylphenol ether carboxylate (NPEC1) ranged from 3200 to 12,000 μg/L, ChVs for lower mole NPE (NPE1,2) ranged from 11 to 500 μg/L, and ChVs for NP ranged from 5 to 3500 μg/L. Using the SSD analysis for NP with higher quality study results, the 10th percentile chronic effect value is 5.7 μg/L, which supports the draft USEPA criteria on NP of 5.9 μg/L.     

Immune Effects of Nonylphenol on Offspring of Rats Exposed During Pregnancy

Effects of nonylphenol on immune system of male rats were examined. Dams were treated orally with nonylphenol at doses of 0, 20, 40, 80, or 200 mg/kg, respectively, from pregnant days 14 to 19. The offspring rats were investigated at postnatal day 60. Compared with the control groups, the doses of 80 and 200 mg nonylphenol/kg induced an obvious decrease in the absolute and relative weight of spleen and thymus. In the 200 mg/kg nonylphenol-treated group, the proliferative responses of murine spleen lymphocytes cultured in vitro were suppressed, Cytokine productions of interferon-gamma and interleukin-6 in serum were markedly lower than those in the control group. Histologically, the boundary between splenic red pulp and white pulp was unclear, expansion and congestion appeared in splenic sinus, lymphocytes in spleen and thymus dramatically reduced, and lots of focal necrosis cells were present. The results of this study show that nonylphenol can cross the placenta barrier, and that in utero exposure to 200 mg/kg/day nonylphenol can inhibit immune function in male offspring rats.