API

Relationship: 1352

Title

?

Altered, Cardiovascular development/function leads to Increase, Mortality

Upstream event

?

Altered, Cardiovascular development/function

Downstream event

?


Increase, Mortality

Key Event Relationship Overview

?


AOPs Referencing Relationship

?


Taxonomic Applicability

?

Term Scientific Term Evidence Link
Danio rerio Danio rerio High NCBI

Sex Applicability

?

Sex Evidence
Unspecific High

Life Stage Applicability

?

Term Evidence
Embryo High
Development High

Key Event Relationship Description

?


  • The cardiovascular system functions in the transport of nutrients, oxygen, carbon dioxide, and hormones to all parts of the organism and is required for survival (Kardong 2006).

Evidence Supporting this KER

?


Biological Plausibility

?

  • A properly functioning cardiovascular system is required for survival of vertebrates and some invertebrates. Therefore, altered development leading to dysfunction would be expected to cause mortality.

Empirical Evidence

?

  • Pumping efficiency of the heart and measured blood cell perfusion rate decreases with increased severity of cardiovascular teratogenesis and increases percent mortality (Dong et al 2010; Teraoka et al 2008).
  • Severe hemorrhage is observable in mortalities as a result of complete cardiac collapse due to cardiovascular teratogenesis (Buckler et al 2015; Elonen et al 1998; Johnson et al 1998; Park et al 2014; Tillitt et al 2016; Toomey et al 2001; Walker et al 1991; Yamauchi et al 2006; Zabel et al 1995).
  • Organisms are significantly less sensitive to mortality due to alteration in cardiovascular development and function post-heart developmental stages (Carney et al 2004; Lanham et al 2012).

Uncertainties and Inconsistencies

?

  • There are numerous different alterations in development or function that can result in mortality. The exact phenotypes that result in lethal versus sub-lethal outcomes is not well known.
  • Nothing is known about differences in altered cardiovascular development and function leading to mortality in invertebrates with open circulatory systems or closed circulatory systems.

Quantitative Understanding of the Linkage

?


  • There is strong quantitative understanding between incidence of and severity of cardiovascular teratogenicity and mortality (Buckler et al 2015; Elonen et al 1998; Johnson et al 1998; Park et al 2014; Tillitt et al 2016; Toomey et al 2001; Walker et al 1991; Yamauchi et al 2006; Zabel et al 1995).
  • However, numerous different cardiovascular endpoints are investigated among studies making side-by-side comparisons difficult.

Response-response Relationship

?

Time-scale

?

Known modulating factors

?

Known Feedforward/Feedback loops influencing this KER

?

Domain of Applicability

?


  • Altered cardiovascular development and function leading to mortality has been extensively demonstrated in numerous teleost and non-teleost fishes and to a lesser extent in birds (Brunstrom 1990; Brunstrom & Andersson 1988; Buckler et al 2015; Cohen-Barnhouse et al 2011; Elonen et al 1998; Hoffman et al 1996; 1998; Huang et al 2012; Johnson et al 1998; Park et al 2014; Powell et al 1998; Tillitt et al 2016; Toomey et al 2001; Walker et al 1991; Yamauchi et al 2006; Zabel et al 1995).
  • Although limited studies are available, altered cardiac development and function leading to mortality is acknowledged to be applicable to reptiles, amphibians, and possibly some invertebrates based on presence of a cardiovascular system.

References

?


Brunstrom, B. (1990). Mono-ortho-chlorinated chlorobiphenyls: toxicity and induction of 7-ethoxyresorufin O-deethylase (EROD) activity in chick embryos. Arch. Toxicol. 64, 188-192.

Brunstrom, B.; Andersson, L. (1988). Toxicity and 7-ethoxyresorufin O-deethylase-inducing potency of coplanar polychlorinated biphenyls (PCBs) in chick embryos. Arch. Toxicol. 62, 263-266.

Buckler J.; Candrl, J.S.; McKee, M.J.; Papoulias, D.M.; Tillitt, D.E.; Galat, D.L. Sensitivity of shovelnose sturgeon (Scaphirhynchus platorynchus) and pallid sturgeon (S. albus) early life stages to PCB-126 and 2,3,7,8-TCDD exposure. Enviro. Toxicol. Chem. 2015, 34(6), 1417-1424.

Cohen-Barnhouse, A.M.; Zwiernik, M.J.; Link, J.E.; Fitzgerald, S.D.; Kennedy, S.W.; Herve, J.C.; Giesy, J.P.; Wiseman, S.; Yang, Y.; Jones, P.D.; Yi, W.; Collins, B.; Newsted, J.L.; Kay, D.; Bursian, S.J. 2011. Sensitivity of Japanese quail (Coturnix japonica), common pheasant (Phasianus colchicus), and white leghorn chicken (Gallus gallus domesticus) embryos to in ovo exposure to TCDD, PeCDF, and TCDF. Toxicol. Sci. 119, 93-102.

Elonen, G.E.; Spehar, R.L.; Holcombe, G.W.; Johnson, R.D.; Fernandez, J.D.; Erickson, R.J.; Tietge, J.E.; Cook, P.M. Comparative toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin to seven freshwater fish species during early life-stage development. Enviro. Toxico. Chem. 1998, 17, 472-483.

Goldstone, H.M.; Stegeman, J.J. 2008. Molecular mechanisms of 2,3,7,8-tetrachlorodibenzo-p-dioxin cardiovascular embryotoxicity. Drug. Metab. Rev. 38 (1), 261-289.

Hoffman, D.J., Rice, C.P., Kubiak, T.J., 1996. PCBs and dioxins in birds. In: Beyer, W.N.,

Heinz, G.H., Redmon-Norwood, A.W. (Eds.), Environmental Contaminants in Wildlife:

Interpreting Tissue Concentrations. CRC Press, pp. 165–207.

Hoffman, D.J., Melancon, M.J., Klein, P.N., Eisemann, J.D., Spann, J.W., 1998. Comparative

developmental toxicity of planar polychlorinated biphenyl congeners in chickens,

American kestrels, and common terns. Environ. Toxicol. Chem. 17, 747–757.

Huang, L.; Wang, C.; Zhang, Y.; Li, J.; Zhong, Y.; Zhou, Y.; Chen, Y.; Zuo, Z. (2012). Benzo[a]pyrene exposure influences the cardiac development and the expression of cardiovascular relative genes in zebrafish (Daniorerio) embryos. Chemosphere. 87 (4), 369-375.

Johnson, R.D.; Tietge, J.E.; Jensen, K.M.; Fernandez, J.D.; Linnum, A.L.; Lothenbach, D.B.; Holcombe, G.W.; Cook, P.M.; Christ, S.A.; Lattier, D.L.; Gordon, D.A. Toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin to early life stage brooke trout (Salvelinus fontinalis) following parental dietary exposure. Enviro. Toxicol. Chem. 1998, 17 (12), 2408-2421.

Kardong, K.V. (2006). Vertebrates: comparative anatomy, function, evolution. McGraw-Hill Higher Eduction. Boston, USA.

Park, Y.J.; Lee, M.J.; Kim, H.R.; Chung, K.H.; Oh, S.M. Developmental toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in artificially fertilized crucian carp (Carassius auratus) embryo. Sci. Totl. Enviro. 2014, 491-492, 271-278.

Powell, D.C., Aulerich, R.J., Meadows, J.C., Tillitt, D.E., Kelly, M.E., Stromborg, K.L.,

Melancon, M.J., Fitzgerald, S.D., Bursian, S.J., 1998. Effects of 3,3′,4,4′,5-

pentachlorobiphenyl and 2,3,7,8-tetrachlorodibenzo-p-dioxin injected into the

yolks of double-crested cormorant (Phalacrocorax auritus) eggs prior to incubation.

Environ. Toxicol. Chem. 17, 2035–2040.

Tillitt, D.E.; Buckler, J.A.; Nicks, D.K.; Candrl, J.S.; Claunch, R.A.; Gale, R.W.; Puglis, H.J.; Little, E.E.; Linbo, T.L.; Baker, M. Sensitivity of lake sturgeon (Acipenser fulvescens) early life stages to 2,3,7,8-tetrachlorodibenzo-p-dioxin and 3,3’,4,4’,5-pentachlorobiphenyl. 2015. Enviro. Toxicol. Chem. DOI: 10.1002/etc.3614.

Toomey, B.H.; Bello, S.; Hahn, M.E.; Cantrell, S.; Wright, P.; Tillitt, D.; Di Giulio, R.T. TCDD induces apoptotic cell death and cytochrome P4501A expression in developing Fundulus heteroclitus embryos. Aquat. Toxicol. 2001, 53, 127-138.

Walker, M.K.; Catron, T.F. (2000). Characterization of cardiotoxicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin and related chemicals during early chick embryo development. Toxicol. Appl. Pharmacol. 167 (3), 210-221.

Walker, M.K.; Spitsbergen, J.M.; Olson, J.R.; Peterson, R.E. 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) toxicity during early life stage development of lake trout (Salvelinus namaycush). Canad. J. Fisheries Aqua. Sci. 1991, 48, 875-883.

Yamauchi, M.; Kim, E.Y.; Iwata, H.; Shima, Y.; Tanabe, S. Toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in developing red seabream (Pagrus major) embryos: an association of morphological deformities with AHR1, AHR2 and CYP1A expressions. Aquat. Toxicol. 2006, 16, 166-179.

Zabel, E.W; Cook, P.M.; Peterson, R.E. Toxic equivalency factors of polychlorinated dibenzo-p-dioxin, dibenzofuran and biphenyl congeners based on early-life stage mortality in rainbow trout (Oncorhynchus mykiss). Aquat Toxicol. 1995. 31, 315-328.