Differences in Sensitivity to Developmental Toxicants as Seen in Xenopus and Pimephales Embryos

Deyoung, Donna J.; Bantle, John A.; Hull, Mendi; Burks, S.L.

doi:10.1007/s001289900021

Cited by 32 publications

(15 citation statements)

References 16 publications

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“…Also, in a water/sediment fate study with radiolabeled 5‐FU, a maximum of 9% of total radioactivity was measured in the river sediment and a maximum of 6.6% in the pond sediment, both on d 5, with consistently lower values later (Mamouni et al 2005), which also argues for low adsorption. Hence, insofar as low adsorption was concluded from 3 of 4 AS studies reported in three publications (IUTA 2000; Fürhacker et al 2006; Mahnik et al 2007), as a further result was equivocal, as low adsorption was registered in the water/sediment study (Mamouni et al 2005), and as low adsorption is predicted based on the negative log K OW s (McKinnon and Kaiser 1993; Pruijn and DeWitte 2004; EPISuite 2007), adsorption is not assumed to be an important removal and fate pathway for 5‐FU, either in WWTPs or in surface waters. Therefore, exposure to soils through surplus AS being spread on land is not seen as a relevant environmental pathway for 5‐FU.…”

Section: Methodsmentioning

confidence: 99%

“…Based on the direct and indirect evidence described above for good biodegradability in WWTPs, 5‐FU was conservatively assigned a biodegradation rate constant k biodeg of 0.1 h −1 , corresponding to an inherently degradable substance, for modeling WWTP removal. The EU WWTP model SimpleTreat (2003) was run with the following basic data for 5‐FU: molecular weight = 130.08 (Roche 2007), K OW = 0.129 based on the measured log K OW of −0.89 (McKinnon and Kaiser 1993; i.e., no change to the default adsorption parameters), a QSAR vapor pressure of 9.50 × 10 −6 Pa (EPISuite 2007), solubility = 11100 mg/L (cited in EPISuite 2007), and K a = 1.0 × 10 −8 based on the p K a of 8.0 (Clarke 2009). SimpleTreat predicts 40.8% biodegraded in a WWTP with primary settler versus 51.9% in a WWTP without primary sedimentation.…”

Section: Methodsmentioning

confidence: 99%

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Combined environmental risk assessment for 5‐fluorouracil and capecitabine in Europe

Straub

2010

Integr Envir Assess & Manag

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An environmental risk assessment (ERA) was made for the old cytostatic active pharmaceutical ingredient 5-fluorouracil (5-FU) and for capecitabine (CAP), which is a prodrug of 5-FU. This ERA is based on published and company internal data as well as new test results for physicochemical, human metabolism, biodegradability, environmental partitioning and fate, and acute and chronic ecotoxicity properties of the active substance 5-FU as well as on use sales data for 5-FU and CAP in Europe. Predicted environmental concentrations (PECs) were extrapolated following the EMEA 2006 Guideline on ERA for human pharmaceuticals and the European Union 2003 Technical Guidance Document (TGD) for risk assessment as well as the TGD-based application EUSES v2.0. Actual amounts sold were taken from IMS Health Databases, in order to refine the default use and EMEA penetration factor as well as the PECs. Moreover, available measured environmental concentrations (MECs) were used to supplement PECs. A predicted no-effect concentration (PNEC) for 5-FU was derived from chronic ecotoxicity data. Except for the simplistic EMEA Phase I default PEC, the risk characterization by PEC:PNEC and MEC:PNEC ratios for various environmental compartments resulted in no significant risk. As the EMEA Phase I PEC does not integrate documented human metabolism and environmental degradation, in contrast to refined PEC derivations, it is inferred that the current use of CAP and 5-FU does not present any evident risk to the environment. An additional evaluation of persistence, bioaccumulation, and toxicity (PBT) properties supports the conclusion of no significant environmental risk for 5-FU and CAP.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Combined environmental risk assessment for 5‐fluorouracil and capecitabine in Europe

Straub

2010

Integr Envir Assess & Manag

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“…Other authors have found that amphibians are, in general, either equally or less sensitive than fish to acute chemical exposures [3][4][5][6][7][8][9][10][11][12][13]29]. For example, Hoke and Ankley [10] found that LC50 values from the frog embryo teratogenesis assay-Xenopus (FETAX) were not the most sensitive result when compared with other acute toxicity endpoints from traditional aquatic test species (including fish) for Cd, Cu, Se, Hg, Zn, ammonia, aniline, pentachlorophenol, atrazine, malathion, and parathion.…”

Section: Acute Toxicitymentioning

confidence: 99%

“…Other authors have also found that amphibians are not usually more sensitive than fish [4][5][6][7][8][9][10][11][12][13]. However, analyses of the relative sensitivity of fish and amphibians using longer-term chronic endpoints have not been undertaken.…”

Section: Introductionmentioning

confidence: 99%

Comparative Acute and Chronic Sensitivity of Fish and Amphibians: A Critical Review of Data

Weltje¹,

Simpson

Gross

et al. 2013

Enviro Toxic and Chemistry

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Abstract-The relative sensitivity of amphibians to chemicals in the environment, including plant protection product active substances, is the subject of ongoing scientific debate. The objective of this study was to compare systematically the relative sensitivity of amphibians and fish to chemicals. Acute and chronic toxicity data were obtained from the U.S. Environmental Protection Agency (U.S. EPA) ECOTOX database and were supplemented with data from the scientific and regulatory literature. The overall outcome is that fish and amphibian toxicity data are highly correlated and that fish are more sensitive (both acute and chronic) than amphibians. In terms of acute sensitivity, amphibians were between 10-and 100-fold more sensitive than fish for only four of 55 chemicals and more than 100-fold more sensitive for only two chemicals. However, a detailed inspection of these cases showed a similar acute sensitivity of fish and amphibians. Chronic toxicity data for fish were available for 52 chemicals. Amphibians were between 10-and 100-fold more sensitive than fish for only two substances (carbaryl and dexamethasone) and greater than 100-fold more sensitive for only a single chemical (sodium perchlorate). The comparison for carbaryl was subsequently determined to be unreliable and that for sodium perchlorate is a potential artifact of the exposure medium. Only a substance such as dexamethasone, which interferes with a specific aspect of amphibian metamorphosis, might not be detected using fish tests. However, several other compounds known to influence amphibian metamorphosis were included in the analysis, and these did not affect amphibians disproportionately. These analyses suggest that additional amphibian testing is not necessary during chemical risk assessment. Environ. Toxicol. Chem. 2013;32:984-994.

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“…Weltje et al (2013) suggest that amphibians are not particularly more sensitive than fish in many cases and were within 2 orders of magnitude -the level of protection applied to fish data for European regulatory purposes. Other researchers have reported similar trends (DeYoung et al 1996;Bridges et al 2002;Kerby et al 2010), although their database of substances was limited. Detailed examinations using dose-response functions or relationships (rather than point estimates) are needed for a more accurate comparison regarding sensitivities between fish and amphibian species.…”

Section: Laboratory Model Development For Amphibiansmentioning

confidence: 88%

A review of ecological risk assessment methods for amphibians: Comparative assessment of testing methodologies and available data

Johnson

Aubee

Salice

et al. 2017

Integr Envir Assess & Manag

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Historically, ecological risk assessments have rarely included amphibian species, focusing preferentially on other aquatic (fish, invertebrates, algae) and terrestrial wildlife (birds and mammal) species. Often this lack of consideration is due to a paucity of toxicity data, significant variation in study design, uncertainty with regard to exposure, or a combination of all three. Productive risk assessments for amphibians are particularly challenging, given variations in complex life history strategies. Further consideration is needed for the development of useful laboratory animal models and appropriate experimental test procedures that can be effectively applied to the examination of biological response patterns. Using these standardized techniques, risk estimates can be more accurately defined to ensure adequate protection of amphibians from a variety of stress agents. Patterns in toxicity may help to ascertain whether test results from 1 amphibian group (e.g., Urodela) could be sufficiently protective of another (e.g., Anura) and/or whether some nonamphibian aquatic taxonomic groups (e.g., fish or aquatic invertebrates) may be representative of aquatic amphibian life stages. This scope is intended to be a guide in the development of methods that would yield data appropriate for ecological risk decisions applicable to amphibians. Integr Environ Assess Manag 2017;13:601-613. © 2016 SETAC.

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Differences in Sensitivity to Developmental Toxicants as Seen in Xenopus and Pimephales Embryos

Cited by 32 publications

References 16 publications

Combined environmental risk assessment for 5‐fluorouracil and capecitabine in Europe

Combined environmental risk assessment for 5‐fluorouracil and capecitabine in Europe

Comparative Acute and Chronic Sensitivity of Fish and Amphibians: A Critical Review of Data

A review of ecological risk assessment methods for amphibians: Comparative assessment of testing methodologies and available data

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