Reproductive toxicity endocrine disruption

RSLs are developed by companies, government agencies, non-profit organizations, and other bodies (such as trade oiganizations). RSLs list chemicals of concern according to various criteria which may vary but often include acute hmnan toxicity, carcinogenicity, mutagenicity, reproductive toxicity, endocrine disruption, eco-toxicity, and persistence and bioaccumulation. 

The priority effects are carcinogenicity, mutagenicity, reproductive or developmental toxicity, endocrine disruption and neurotoxicity. Human toxicity is broader than priority effects, including acute toxicity, systemic toxicity (organ effects), immune system effects and skin/eye/respiratory damageaswellasthepriority effects. And toxicity as T includes both human toxicity and ecotoxicity. 

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). 

Priority Effects = carcinogenicity, mutagenicity, reproductive or developmental toxicity, endocrine disruption, or neurotoxicity... 

Another section of the EPA, the Office of Prevention, Pesticides, and Toxic Substances (OPPT), has recently updated and harmonized its testing guidelines for evaluating the developmental and reproductive effects of pesticides and industrial chemicals to include an assessment of endocrine disrupting properties. These guidelines will be used in future testing of pesticides under both the Toxic Substances Control Act (TSCA) and the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA). 

Exposure to estrogenic compounds through diet will differ for herbivores and carnivores, the latter being most likely to encounter endogenous steroids in their prey. Efficient uptake of steroids in mammals is illustrated by the use of the contraceptive pill, but routes of absorption in invertebrates remain to be determined. The relationship between endocrine disruption and metabolic toxicity, with reduced reproductive viability a secondary consequence of metabolic disturbance, also merits further study in invertebrate species. 

Many pesticides cause endocrine disruption in vertebrate and invertebrate species at concentrations that are not overtly metabolically toxic. The insect growth inhibitor diflubenzuron can affect the reproduction, development and behaviour of estuarine crustaceans at concentrations of just lOmgP (reviewed... 

In addition to their endocrine disrupting properties, it must be appreciated that many of the chemicals in question possess more general toxic properties, which may be potentiated by metabolism by the organism. Several PAHs, PCBs and PCDDs are carcinogenic, while certain phthalate esters can enhance the excretion of zinc, potentially leading to zinc deficiency. Zinc, an essential element, plays a vital role in spermatogenesis and mature T-cell production. Deficiency may result in abnormalities of the male reproductive system, depletion of spermatogenesis and suppression of the immune system. 

The majority of very high concern substances will be those classified as category 1 or 2 CMRs. There are already around 850 such CMR substances based on current classifications, and it is likely that there will be another ca 500 identified from future testing. Most endocrine disrupters would require authorisation by being classified as carcinogenic or toxic for reproduction, but there is the option to add other endocrine disruptors on an ad hoc basis. 

Article 54 a-f. Criteria for chemicals to be added to Annex XI11 and thus require authorisation category 1 or 2 carcinogens, category 1 or 2 mutagens, category 1 or 2 reproductive toxins, substances which are persistent, bloaccumulative and toxic, very persistent and very bloaccumulative, endocrine disrupting or of equal concern. 

In the OECD Draft Guidance Document on Reproductive Toxicity Testing and Assessment (OECD 2004d), the term endocrine disruption is defined as above. 

Secondary to the societal concerns around chemical-related endocrine disruption, the OECD407 subacute 28-day toxicity study protocol has been updated in 2007 with parameters relating to endocrine homeostasis. Specifically, circulating thyroid hormones and detailed assessment of reproductive organ parameters were added to the protocol. Reproductive hormones were suggested as additional parameters but they were deemed not informative in view of their large variability in untreated animals. 

Novic, M. and Vracko, M. (2010) QSAR models for reproductive toxicity and endocrine disruption activity. Molecules, 15 (3), 1987-1999. 

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