Endocrine active substances

Gourmelon, A. and Ahtiainen, 1. (2007). Developing Test Guidelines on invertebrate development and reproduction for the assessment of chemicals, including potential endocrine active substances—The OECD perspective. Ecotoxicology 16, 161-167. 

J. M.Z. and Crane, M. (2009) Thresholds of toxicological concern for endocrine active substances in the aquatic environment. Integr Environ Assess Manage, 6, 2-11. 

Mazur, W. and Adlercreutz, H., Overview of naturally occurring endocrine-active substances in the human diet in relation to human health. Nutrition, 16, 654-687, 2000. 

The mechanism by which the endocrine and metabolic response is activated has not been defined clearly. There is evidence that both neural impulses and tissue substances play a part in stimulating what is virtually a total increase in endocrine activity. Many of the hormones which are increased have metabolic functions which include the maintenance of blood glucose levels. This appears to be a fundamental biological defense mechanism whereby an essential energy source is preserved for the central nervous system. 

REACH substance evaluation can apply to the active substance if it has been prioritized and placed on the Community Rolling Action Plan, and active substances used in biocidal products may be included in Annex XIV of REACH if they are classified as CMR, PBT, vPvB, or endocrine disrupters. 

Figure 1.2 Usage of selected pesticides in the United Kingdom between 1983 and 1997. The data are expressed as kilogrammes of active substance applied. The compounds included are carbaryl, dicofol, quinalphos, parathion, gamma-HCH, DDT, methoxy-chlor, amitrole, metribuzin, atrazine, linuron, diuron, 2,4,5-T, 2,4-D, nitrofen, trifluralin, fenarimol, sodium 2-phenylphenoxide, vinclozolin, ziram, zineb-ethylenethiuram disulfide zineb, thiram, maneb and mancozeb. Each has been alleged to exhibit some endocrine-disrupting properties...

There is particular concern that the pharmacodynamic activities of some drugs may be expressed in consumers, and this concern has been paramount over the presence of hormonally active substances, and particularly those with the capacity to act as endocrine disrupters in humans or indeed, in environmental organisms. There is a considerable body of concerns that include adverse effects on sexual, thyroid, adrenal and reproductive function in humans and other animals, as well as genital abnormalities e.g. hypospadias) and effects on embryonic and foetal development. This has led to the tighter regulation of human pharmaceutical products in a number of countries from the point of view of environmental effects and environmental assess-... 

H. A. Greim, The endocrine and reproductive system adverse effects of hormonally active substances . Pediatrics, 2004, 113(Supplement), 1070-1075. 

Humoral or hormonal control means that peripheral tissue is influenced by substances with specific effects. These active substances are formed in specialized glands or tissues (endocrine glands) and secreted into the blood stream. This can also be called interruil secretion ] the substances produced by endocrine (or endo-secretory) glands are the hormones. 

The posterior lobe of the pituitary, ie, the neurohypophysis, is under direct nervous control (1), unlike most other endocrine organs. The hormones stored in this gland are formed in hypothalamic nerve cells but pass through nerve stalks into the posterior pituitary. As early as 1895 it was found that pituitrin [50-57-7] an extract of the posterior lobe, raises blood pressure when injected (2), and that Pitocin [50-56-6] (Parke-Davis) causes contractions of smooth muscle, especially in the utems (3). Isolation of the active materials involved in these extracts is the result of work from several laboratories. Several highly active posterior pituitary extracts have been discovered (4), and it has been deterrnined that their biological activities result from peptide hormones, ie, low molecular weight substances not covalendy linked to proteins (qv) (5). 

Vasopressin (antidiuretic hormone) is a peptide synthesized in the hypothalamus and secreted from the neurohypophysis of the pituitary gland. This substance plays an important role in the long-term regulation of blood pressure through its action on the kidney to increase reabsorption of water. The major stimulus for release of vasopressin is an increase in plasma osmolarity. The resulting reabsorption of water dilutes the plasma toward its normal value of 290 mOsM. This activity is discussed in more detail in Chapter 10 (the endocrine system) and Chapter 19 (the renal system). 

Although the kidneys are not considered endocrine glands per se, they are involved in hormone production. Erythropoietin is a peptide hormone that stimulates red blood cell production in bone marrow. Its primary source is the kidneys. Erythropoietin is secreted in response to renal hypoxia. Chronic renal disease may impair the secretion of erythropoietin, leading to development of anemia. The kidneys also produce enzymes. The enzyme renin is part of the renin-angiotensin-aldosterone system. As will be discussed, these substances play an important role in the regulation of plasma volume and therefore blood pressure. Other renal enzymes are needed for the conversion of vitamin D into its active form, 1,25-d i hyd ro xyv itamin D3, which is involved with calcium balance. 

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