Experimental and epidemiological studies suggest that some man-made and naturally occurring chemicals related to the environment have the potential to interrupt normal functioning of the endocrine systems of humans and wildlife. These chemicals, termed EDCs (Endocrine disrupting Chemicals), pose serious threats to the reproductive capability of humans and wildlife. Because of the structural diversity and various types, development of structure-based rapid screening methodologies is important and necessary for the assessment of the environmental pollutants. In this paper molecular hologram based QSAR models were developed with the combinatory application of partial least square (PLS) regression for a large diverse set of 105 environmental estrogens. Quantitatively predictive models were developed based on only molecular structures, which can be used for the accurate prediction of estrogenicity to rapidly screen potential environmental endocrine disrupting chemicals.