Screening for potential endocrine disruptors in fish: evidence from structural alerts and in vitro and in vivo toxicological assays

Nendza, Monika; Wenzel, Andrea; Müller, Martin; Lewin, Geertje; Simetska, Nelly; Stock, Frauke; Arning, Jürgen

doi:10.1186/s12302-016-0094-5

Environmental Sciences Europe

Table 3 Comparison of in vivo long-term reproduction studies with mammals and fish with results from receptor-based in vitro assays

From: Screening for potential endocrine disruptors in fish: evidence from structural alerts and in vitro and in vivo toxicological assays

Compound	CAS no.	Mechanism	Mammalian reproductive toxicology	Fish in vivo effects			Reporter gene (cell) assays			Receptor-binding studies
			Mammalian reproductive toxicology	Fish full and partial life-cycle (FLC) test		Fish screening assay (FSA)	Potency relative to positive control			Potency relative to positive control
			In vivo ED effect LOAEL	NOEC/EC₁₀ population	NOEC indicator parameter	Effect	ER agonist	AR agonist	AR antagonist	ER	AR
17-α Ethinylestradiol	57-63-6	ER agonist	Pos.-control in screening assays (OECD 440)	0.3 ng/L, fertilization rate, delayed oviposition [41]	1 ng/L, ovotestis [42]	VTG increase [27]	Very active [43]		No [28]	Very active [5]	Moderate [21]
17-β Estradiol	50-28-2	ER agonist	0.0025 mg/kg BW	2.9 ng/L, fertilization rate, juvenile growth [44]	2.9 ng/L, VTG induction, males [44]		Very active [45]	Moderate [28]	Active [18]	Very active [5]	Active [21]
Tamoxifen	10540-29-1	ER antagonist	0.00012 mg/kg BW	1.6 µg/L, fertilization rate [27]	1.6 µg/L, VTG decrease, females [27]	VTG decrease [27]	Moderate [43]		Moderate [46]	Very active [21]	Active [46]
Genistein	446-72-0	ER agonist, enzyme inhibitor: aromatase	1.25 mg/kg BW	1.3 µg/L, fertilization rate, delayed oviposition [27]			Moderate [47]			Very active [21]	Moderate [21]
Methyl-testosterone	58-18-4	AR agonist		10 ng/L, sex ratio [48]	<0.4 ng/L, VTG decrease, females [48]		Active [49]	Active [49]			Very active [21]
17β-Trenbolone	10161-33-8	AR agonist	1.68 mg/kg BW	3 ng/L, sex ratio [50]	<1 ng/L, histology: egg debris [50]	VTG and 11-keto-testosterone: no effect [27]		Active[28]			Very active [21]
Flutamide	13311-84-7	AR antagonist	2.5 mg/kg BW	189 µg/L, egg production [27]	435 µg/L, VTG decrease, females, 11-keto-testosterone: increase [27]	VTG no effect, 11-keto-testosterone: increase [27]		Weak [28]	Very active [28]		Moderate [21]
Bisphenol A	80-05-7	ER agonist	0.0002 mg/kg BW	390 µg/L, fertilization rate, delayed oviposition [51] 160 µg/L, hatching rate of F1 generation [52]	1 µg/L, histology: testis, VTG increase, males [52]	VTG increase, 11-keto-testosterone: decrease [27]	Moderate [53]	Very weak [54]	Active [18]	Moderate [5, 21]	Moderate [21]
4-tert-Pentylphenol	80-46-6	ER agonist		100 µg/L, fertilization rate, sex ratio [55]	<51 µg/L, VTG increase, males [55]				Active [18]	Moderate [5, 21]	Moderate [21]
4-tert-Octylphenol	140-66-9	ER agonist		11 µg/L, fertilization rate, delayed oviposition [27]		VTG increase, 11-keto-testosterone: decrease [27]	Moderate [56]	Very weak [57]	Active [18]	Moderate [5, 21]	Moderate [21]
4-Nonylphenol	84852-15-3	ER agonist	10 mg/kg BW	8.2 µg/L, sex ratio, survival rate [58]	4.2 µg/L, gonadosomatic index [58]		Moderate [59]	Very weak [60]	Very weak [60]	Moderate [21]	Moderate [21]
Prochloraz (DMI fungicide)	67747-09-5	Aromatase inhibitor		64 µg/L, sex ratio [61]	<16 µg/L, VTG increase, males [61]	VTG decrease [27]	Very weak [62]		Very weak [62]

Mammalian reproductive toxicology from: http://cefic-lri.org/lri_toolbox/fedtex/, http://www.fraunhofer-repdose.de/
Relative potencies in receptor-based in vitro assays: substances were categorized based on their in vitro potencies in individual tests, relative receptor-binding affinities, or effect concentrations relative to positive controls, ethinylestradiol (estrogenic) or testosterone (androgenic), respectively (Table 1)
LOAEL lowest observed adverse effect level, NOEC no observed effect concentration, ER estrogen receptor, AR androgen receptor, VTG vitellogenin, DMI fungicide demethylation inhibitor (sterol synthesis inhibitor)

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