Table 7.
Examples of NMDRCs in animal studies
| Chemicals by chemical class | Nonmonotonic effect | Organ/sex/animal | Refs. |
|---|---|---|---|
| Natural hormones | |||
| 17β-Estradiol | Morphological parameters | Mammary gland/female/mice | 138, 541 |
| Accumulation of cAMP | Pineal/female/rats | 760 | |
| Prostate weight | male/mice | 689 | |
| Uterine weight | female/mice | 761 | |
| Antidepressant effects, measured by immobility assay | Behavior/male/mice | 762 | |
| Nocturnal activity, gene expression in preoptic area | Brain and behavior/female/mice | 763 | |
| Corticosterone | Spatial memory errors | Behavior/male/rats | 764 |
| Cholinergic fiber loss in cortex after treatment with neurodegenerative drugs | Brain/male/rats | 765 | |
| Mitochondrial metabolism | Muscle/male/rats: strain differences | 766 | |
| Contextual fear conditioning | Behavior/male/rats | 767 | |
| Locomotor activity | Behavior/male/captive Adelie penguins | 768 | |
| Glucocorticoid | Na+/K+-ATPase activity | Brain/tilapia (fish) | 769 |
| Testosterone | Na+/K+-ATPase activity | Brain/tilapia (fish) | 769 |
| Gonadotropin subunit gene expression | Pituitary/sexually immature goldfish | 770 | |
| 11β-Hydroxyandrosterone | Gonadotropin subunit gene expression | Pituitary/sexually immature goldfish | 770 |
| T4 | Bone growth | Tibia/male/rats with induced hypothyroidism | 771 |
| Leptin | Insulin production (in the presence of glucose) | Pancreas/male/rats | 560 |
| Oxytocin | Infarct size, plasma LDH levels, creatine kinase activity after ischemia/ reperfusion injury | Brain and blood/male/rats | 772 |
| Memory retention | Behavior/male/mice | 773 | |
| Melatonin | Brain infarction and surviving neuron number after injury | Brain/female/rats | 774 |
| Dopamine | Memory | Brain/both/rhesus monkey | 775 |
| Neuronal firing rate | Brain/male/rhesus monkey | 776 | |
| Pharmaceutical | |||
| DES | Sex ratio, neonatal body weight, other neonatal development | Mice | 777 |
| Adult prostate weight | Male/mice | 689 | |
| Uterine weight | Female/mice | 761 | |
| Expression of PDGF receptor | Testes/male/rats | 778 | |
| Morphological parameters | Mammary gland/male and female/mice | 779 | |
| Estradiol benzoate | Dorsal prostate weight, body weight | Male/rats | 780 |
| Sexual behaviors, testes morphology | Male/zebra finches (birds) | 781 | |
| Ethinyl estradiol | GnRH neurons | Brain/zebrafish | 782 |
| Tamoxifen | Uterine weight | Female/mice | 761 |
| Fluoxetine (antidepressant) | Embryo number | Potamopyrgus antipodarum (snails) | 783 |
| Fadrozole (aromatase inhibitor) | Aromatase activity | Ovary/female/fathead minnows | 784 |
| Plastics | |||
| BPA | Fertility | Reproductive axis /female/mice | 316 |
| Reproductive behaviors | Behavior/male/rats | 785 | |
| Protein expression | Hepatopancreas/male/Porcellio scaber (isopod) | 786 | |
| Timing of vaginal opening, tissue organization of uterus | Reproductive axis/female/mice | 577 | |
| Expression of receptors in embryos | Brain and gonad/both/ mice | 787 | |
| DEHP | Aromatase activity | Hypothalamus/male/rats | 788 |
| Cholesterol levels | Serum/male/rats | 569 | |
| Timing of puberty | Reproductive axis /male/rats | 789 | |
| Body weight at birth, vaginal opening, and first estrous | Female/rats | 790 | |
| Seminal vesicle weight, epididymal weight, testicular expression of steroidogenesis genes | Male/rats | 791 | |
| Responses to allergens, chemokine expression | Skin/male/mice | 792 | |
| Detergents, surfactants | |||
| Nonylphenol ethoxylate | Fecundity | Biomphalaria tenagophila (snails) | 793 |
| Octylphenol | Embryo production | P. antipodarum (snails) | 794 |
| Spawning mass and egg numbers | Marisa cornuarietis (snails) | 795 | |
| Semicarbazide | Timing of preputial separation, serum DHT | Male/rats | 796 |
| Antimicrobial | |||
| Triclocarban | Fecundity | P. antipodarum (snails) | 797 |
| PCB | |||
| Mixture of PCB | Corticosterone levels | Male/kestrels (birds) | 798 |
| Environmental PCB mixture | Corticosterone levels | Female/tree swallows (birds) | 799 |
| UV filters | |||
| Octyl methoxycinnamate | Activity, memory | Behavior/both/rats | 800 |
| Aromatic hydrocarbons | |||
| Β-naphthoflavone | Testosterone | Plasma/male/goldfish | 736 |
| Toluene | Locomotor activity | Behavior/male/rats | 801 |
| Dioxins | |||
| TCDD | Cell-mediated immunity | Immune system/male/ rats | 802 |
| Proliferation after treatment with chemical carcinogen | Liver/female/rats | 803 | |
| Heavy metals | |||
| Cadmium | Expression of metallothionein, pS2/TFF1 | Intestine and kidney/ female/rats | 804 |
| Activity of antioxidant enzymes | Earthworms | 805 | |
| Size parameters, metamorphic parameters | Xenopus laevis | 806 | |
| Lead | Growth, gene expression | Vicia faba seedlings (plant) | 807 |
| Retinal neurogenesis | Eye and brain/female/rats | 808 | |
| Selenium | DNA damage, apoptotic index | Prostate/male/dogs | 809 |
| Hatching failure | Eggs/red-winged blackbirds (wild population) | 810 | |
| Phytoestrogens | |||
| Genistein | Aggressive, defensive behaviors | Behavior/male/mice | 811 |
| Retention of cancellous bone after ovariectomy | Tibia bones/female/rat | 812 | |
| Expression of OPN, activation of Akt | Prostate/male/mice | 740 | |
| Resveratrol | Angiogenesis | Chorioallantoic membrane/chicken embryos | 742 |
| Ulcer index after chemical treatment, expression of gastroprotective genes | Stomach/male/mice | 813 | |
| Phytochemicals | |||
| Phlorizin | Memory retention | Behavior/male/mice | 814 |
| Herbicides | |||
| Atrazine | Time to metamorphosis | Thyroid axis/Rhinella arenarum (South American toad) | 815 |
| Survivorship patterns | Four species of frogs | 363 | |
| Growth parameters | Bufo americanus | 816 | |
| Pendimethalin | Expression of AR, IGF-I | Uterus/female/mice | 817 |
| Commercial mixture with mecoprop, 2,4-dichlorophenoxyacetic acid and dicamba | Number of implantation sites, number of live births | Female/mice | 818 |
| Simazine | Estrous cyclicity | Reproductive axis/female/rat | 819 |
| Insecticides | |||
| Permethrin | Dopamine transport | Brain/male/mice | 820 |
| Heptachlor | Dopamine transport | Brain/male/mice | 820 |
| DDT | Number of pups, sex ratios, neonatal body weight, male anogenital distance | Mice | 777 |
| Methoxychlor | Number of pups, anogenital distance (males and females), neurobehaviors (males and females) | Mice | 777 |
| Chlorpyrifos | Body weight | Male/rats | 821 |
| Antioxidant enzyme activity | Oxya chinensis (locusts) | 822 | |
| Malathion | Antioxidant enzyme activity | O. chinensis (locusts) | 822 |
| Fungicides | |||
| Carbendazim | Liver enzymes, hematology parameters | Blood and liver/male/rats | 823 |
| Chlorothalonil | Survival, immune response, corticosterone levels | Several amphibian species | 686 |
| Vinclozolin | Protein expression | Testes/male/P. scaber (isopod) | 786 |
Due to space concerns, we have not elaborated on the shape of the curve (U, inverted U, or other nonmonotonic shape) or the magnitude of observed effects in this table. DEHP, Bis(2-ethylhexyl) phthalate; DHT, dihydrotestosterone; LDH, lactate dehydrogenase; PCB, polychlorinated biphenyl; PDGF, platelet-derived growth factor.