Endocrine Survey

This test is applied for the detection of biological effects related to previous indications from in vitro pharmacology, and from animal studies performed with the tests substance. 

When a distinct endocrine profile of a compound is present before starting the toxicology studies, a targeted investigation can be added to the standard toxicology protocol, satellite groups may be added, or specific mechanistic studies may be initiated in the context of toxicological evaluation of the test substance. 

In this method, the repeated dose administration with a design similar to toxicology studies is preferred. Studies of up to four weeks duration need to include function tests for hormone secretion (basal concentrations, stimulation or inhibition), and for hormone contents of endocrine organs and tissues (e.g. hypothalamus, pituitary gland, reproductive organs). In the Endocrine Survey, 5 to 7 days of treatment are mandatory because adaptation and response of hormone-dependent organs to the treatment requires that a steady state be reached. Repeated-dose treatment with at least two doses is also needed for a sufficient 

The inclusion of untreated or a vehicle control groups is always mandatory. The additional inclusion of comparator groups (comparators of known endocrine activity) may be considered. In me majority of cases this is however not necessary, because mere is an extensive data base in me literature about me effect size of established drugs mat affect me endocrine systems. This agrees with me guideline statement in well-characterised in vivo test systems, positive controls may not be necessary . 

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Table 1 Endocrine Survey study, hormone systems to be investigated after repeated-dose treatment, optional biomarkers to be included in the investigation during the study and at autopsy...

The Endocrine Survey is a flexible approach to the investigation of several hormonal systems in one study, it is closely related to the design of subchronic toxicology studies, however with the specific focus on endocrine systems. 

Sarmah AK, Northcott GL, Leusch FDL, Tremblay LA (2006) A survey of endocrine disrupting chemicals (EDCs) in municipal sewage and animal waste effluents in the Waikato region of New Zealand. Sci Total Environ 355 135-144... 

Langdon KA, Wame MS, Smemik RJ, Shareef A, Kookana RS (2011) Selected personal care products and endocrine disruptors in biosolids an Australia-wide survey. Sci Total Environ 409 1075-1081... 

Kirby, M.F., Allen, Y.T., Dyer, R.A., Feist, S.W., Katsiadiki, I., Matthiessen, P., Scott, A.P., Smith, A., Stentiford, G.D., Thain, J.E., Thomas, K.V., ToUiurst, L., Waldock, M.J. (2004). Surveys of plasma vitellogenin and intersex in male flounder (Platichthys flesus) as measures of endocrine disruption by estrogenic contamination in United Kingdom estuaries temporal trends, 1996 to 2001. Environmental Toxicology and Chemistry, 23 748-758. 

The investigation provided evidence of limited migration of both TPA and IPA. The UK Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT) advised that the levels of TPA and IPA found in foods in this survey were not of concern for public health based on available information. Nevertheless, they recommended that further studies be carried out for TPA and IPA to see if they have endocrine disrupter activity. 

Notes B1 = survey on the actual condition of chemical substances in the environment (until 2001) B2 = survey on the actual condition of chemical substances in the environment (after 2002) D = survey under the Law concerning Special Measures against Dioxins E = survey on the environmental endocrine disrupters W = survey under the Water Pollution Control Law A = the air pollutants monitoring O = other survey. Details of the survey on the actual condition of chemical substances in the environment refer to Ministry of the Environment web site http // www.env.go.jp/chemi/kurchen/index.html (also refer to annual reports before FY1996). 

Details of the survey on the environmental endocrine disrupters refer to working group materials on the Ministry of the Environment web site http //www.env.go.jp/chemi/end/index2.html... 

The government has been measuring PCB, HCB, DDT, chlordane, heptachlor epoxide and dieldrin since 1998 to identify their effects on wildlife as part of the Environmental Survey on Endocrine Disruptors. The specimens taken include land animals such as raccoons, bears, monkeys and frog, and marine mammals such as seals and whales, in addition to domestic birds and birds of prey. A relatively high concentration of POPs was seen in birds of prey and Phalacrocorax carbo. Eggs of mountain hawk eagles were also found to have a higher concentration of PCB, DDT, heptachlor epoxide, chlordane and dieldrin than other wildlife specimens... 

Ministry of the Environment, Japan, 1998. Environmental monitoring survey of exogenous endocrine disrupting chemicals English version http //www.env.go.jp/en/chemi/ed/ eeds/MonitoringSurvey.html (results of 1998 survey). 

Ratnaningsih, D., Helmy, M., Bagus, B.E., Nety, W., Heni, P., 2002. A survey on water pollution by endocrine disrupter compounds Monitoring of organochlorine pesticides,... 

The National Dioxin Program has extensively surveyed the levels of dioxins in Australian foods, human milk and the natural environment as well as identifying sources. As a result of this the risks to human health and the natural environment are considered to be minimal. Human health risks from exposure to POPs may continue to be an issue, because of increasing concerns about endocrine disruption and also the possible relationship between residues and specific cancers such as breast cancer. 

Petrovic, M., E. Eljarrat, MJ. Lopez de Alda, et al. 2004. Endocrine disrupting compounds and other emerging contaminants in the environment A survey on new monitoring strategies and occurrence data. Anal. Bioanal. Chem. 378 549-562. 

One of the groups of suspect chemicals in the most active effluents in the survey was the alkyl phenols. However, there are probably several endocrine disrupting chemicals in the effluents and rivers, as different waste treatment plants may feed into the same river. As well as the alkyl phenols, a large number and variety of chemicals have been found to cause this effea, including organochlorine insecticides such as DDT, organotin compounds, phthalate esters, plant products, dioxins, polycyclic aromatic hydrocarbons, PCBs, and as expected natural and synthetic oestrogens. 

Endocrine. Endocrine changes may be identified by inclusion of specific hormone analyses (based on availability of bioanalytical methods for the species) in toxicology studies, or more typically by histopathologic evaluation of endocrine organs. Results from the multinational industry survey showed only moderate concordance (60 percent) from preclinical studies.7 Fletcher reported that the findings from preclinical toxicology studies overpredicted effects in humans.14... 

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