Teratogenic endocrine effects

Another important source of information on the status of alternative test development, with particular emphasis on the requirements for cosmetics testing, is a review paper published in 2011 by Adler and coauthors [9], Table 1 summarizes those relevant for reproductive toxicity. Several assays refer to the detection of endocrine effects on steroidogenesis based on a variety of cell types, and, as already mentioned, they will be dealt with in another chapter of this book. The other tests can be subdivided in placental toxicity/transport, preimplantation toxicity, female and male toxicity, and developmental toxicity. The tests that are suitable for detecting developmental toxicity include the EST, the whole-embryo assay, the micromass test (all three already described above), the zebrafish embryo teratogenicity assay, and the frog embryo teratogenesis assay (FETAX). 

Toxicology LD50 (oral, rat) 5000 mg/kg, (IP, rat) 2750 m kg, (subcut., rat) 3600 mg/kg, (IV, mouse) 4015 mg/kg mod. toxic by IP and subcut. routes mildly toxic by ing., IV routes harmful by ing., inh., skin contact irritating to eyes, skin, respiratory system may cause Gl, liver, or endocrine changes, wt. loss, body temp, decrease experimental teratogen, reproductive effects mutagenic data TSCA listed... 

Human toxicity Acute effects Carcinogenicity Genotoxicity/mutagenicity Developmental Teratogenicity/mutagenicity Neurotoxicity Endocrine disruption... 

Episodic pollution events can adequately be addressed by acute toxicity bioassays, however these are not sufficient to investigate the water quality for delayed toxicity effects of chemicals present. Chronic effects of pesticides can include carcinogenicity, teratogenicity, mutagenicity, neurotoxicity, and reproductive effects (endocrine disruption). 

SAFETY PROFILE Poison by ingestion, intravenous, intraperitoneal, and subcutaneous routes. Human systemic effects by intravenous route anorexia, hallucinations and distorted perceptions, thrombosis, nausea or vomiting, fatty liver degeneration, impaired liver function, endocrine changes, and leukopenia (reduced white blood cell count). An experimental teratogen. Experimental reproductive effects. Mutation data reported. When heated to decomposition it emits acrid smoke and fumes. 

SAFETY PROFILE Poison by intravenous route. Moderately toxic by ingestion and intraperitoneal routes. Human teratogenic effects by ingestion developmental abnormalities of the endocrine system. Experimental teratogenic and reproductive effects. Mutation data reported. Explosive reaction with charcoal + ozone, trifluoroacetyl hypofluorite, fluorine perchlorate. Violent reaction or ignition on contact with diazonium salts, diisopropyl peroxydicarbonate, bromine pentafluoride, chlorine trifluoride. Incompatible with oxidants, BrFs, FCIO, metallic salts, calomel. When heated to decomposition it emits very toxic fumes of K20 and I . See also IODIDES. 

Mancozeb has effects on various organ systems. Its primary mechanism of toxicity is via skin contact, leading to contact dermatitis and dermal sensitization. Mancozeb has also been shown to have teratogenic and reproductive effects. Mancozeb exposure also alters the reproductive and endocrine structures, leading to decreased fertility. Animals orally exposed to mancozeb showed thyroid hyperplasia, probably via its ability to inhibit the synthesis of thyroxin. Additionally, mancozeb exposure produces neurotoxicity via yet an unknown mechanism. 

One study that overcomes some of the shortcomings of those just cited reported adverse neurodevelopment outcomes following maternal exposures to 19 organic solvents and mixtures of these. 13 In this study, the women were occupationally exposed to the chemicals listed in Table 24.3. Also included in this table are the K, values and whether or not the specific chemical is a known teratogen or a known endocrine disruptor. 5 It is interesting to note that only three of the chemicals in the study—ethanol, trichloroethylene, and mineral spirits (a mixture of hydrocarbon solvents)—are endocrine disruptors. This shows that teratogenic effects can be induced by chemicals and mixtures that are independent of the endocrine system. 

The target organs and mode of action of OTC have been discussed and can be summarized as follows the most toxic compounds tetramethyltin (TMT) and tetraethyltin (TET) are highly neurotoxic in mammals there is evidence for the hepatotoxicity of DBT in animal models the butyltin and TPhT compounds have been shown to be immunotoxic in mammals TPT is classed by the US Environmental Protection Agency as a probable human carcinogen there is some evidence that TPT exhibits endocrine-disrupting properties in rats and the butyltin compounds exhibit teratogenic effects in mammals. However, it is very apparent from reviews in the area that the chronic effects of the widely dispersed butyltin compounds have not been studied in detail and their effects on humans are consequently not well understood. 

Cadmium has a diversity of toxic effects including nephrotoxicity, carcinogenicity, teratogenicity, and endocrine and reproductive toxicities. Although cadmium is not essential for growth and development in mammals, it generally followes the metabolic pathways of the essential elements zinc and copper. 

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