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Animal Studies
Many harmful effects have been observed in animals exposed to 2-butoxyethanol.

Developmental effects were seen in a study by Ty et al. This study exposed pregnant Fischer 344 rats and New Zealand white rabbits to varying doses of 2-butoxyethanol. At 100 ppm (483 mg/m3) and 200 ppm (966 mg/m3) exposure, there were statistically significant increases in the number of litters with skeletal defects. Additionally, 2-butoxyethanol was associated with a significant decrease in maternal body weight, uterine weight, and number of total implants.

Neurological effects have also been observed in animals exposed to 2-butoxyethanol. In a study by Dodd et al., Fischer 344 rats were exposed to 2-butoxyethanol at concentrations of 523 ppm and 867 ppm. Both female and male rats experienced decreased coordination after this exposure. Similarly, in a study by Dow et al., male rabbits showed a loss of coordination and equilibrium after exposure to 400 ppm of 2-butoxyethanol for 2 days.

When exposed to 2-butoxyethanol in drinking water, both F344/N rats and B63F1 mice showed negative effects. The range of exposure for the two species was between 70 mg/kg body weight per day to 1300 mg/kg body weight per day. Decreased body weight and water consumption were seen for both species. For rats, there were reduced red blood cell counts and thymus weights, as well as lesions in the liver, spleen, and bone marrow.

Koller's sickle is a local thickening of cells in the area pellucida that acts as a margin separating sheets of cells from posterior margin of avian blastoderms from hypoblasts and area opaca endoderm. The blastoderm is a single layer of cells, and the hypoblast and area opaca endoderm cells lie directly below the blastoderm. Koller's sickle arises from the mid-point, between the hypoblast cells and the area opaca endoderm. As blastoderm cells migrate anteriorly and push primary hypoblast cells, which forms a secondary hypoblast known as the endoblast, Koller's sickle is responsible for preventing the hypoblast cells and the area opaca cells from making contact with the blastoderm, which allows the primitive streak to form. This happens in avian gastrulation, a process by which developing cells in an avian embryo move relative to one another in order to form the three germ layers (endoderm, mesoderm, and ectoderm).

Gene influence
While a single gene has not been isolated for the creation of Koller's sickle, there is evidence that the Homeobox gene Hex influences Koller's sickle development. The transcript cHex, which is a product of Hex, has been detected in Koller's sickle during chick embryogenesis. cHex is also involved with the formation of the hypoblast, the endoderm in an anterior arc that overlaps the cardiogenic region, pharyngeal endoderm immediately adjacent to the forming myocardium, in the endocardium, and in the liver and thyroid gland primordia.

Current research
There is still a lot that is unknown regarding Koller's sickle, but research is ongoing. By implanting a fragment of quail Koller's sickle into a chicken blastoderm, Drs. Callebaut and Van Nueten observed the formation of a normal secondary primitive streak, mesoderm, and definitive endoderm. This led them to the conclusion that Koller's sickle is the early avian representation of the organizer, and that there is homology between Koller's sickle in avians and the blastoporus in amphibians. Drs. Callebaut and Van Nueten also optimized a method for preparation of unincubated avian eggs, and from this they demonstrated the fact that embryonic regulation is a result of the spatial distribution of Koller's sickle tissue. Additionally, Drs. Callebaut and Van Nueten were able to determine that the differentiation of Koller' sickle cells to sickle endoblast is irreversible, and that the sickle endoblast induces early neurulation; they did this by implanting Koller's sickle tissue into different parts of unincubated chicken blastoderms and observing the effects.

Koller's sickle
In avian gastrulation, Koller's sickle is a local thickening of cells at the posterior edge of the area pellucida, specifically the upper layer, which is called the epiblast. Koller's sickle is crucial for avian development, due its critical role in inducing the differentiation of various avian body parts.

In depth definition
The thickening of the epiblast in Koller's sickle acts as a margin separating sheets of cells from posterior side of avian blastoderms from hypoblasts and area opaca endoderm. The blastoderm is a single layer of cells, and the hypoblast and area opaca endoderm cells lie directly below the blastoderm. Koller's sickle arises from the midpoint, between the hypoblast cells and the area opaca endoderm. As blastoderm cells migrate anteriorly they push primary hypoblast cells and form a secondary hypoblast known as the endoblast. Also during this migration, Koller's sickle prevents the hypoblast cells and the area opaca cells from making contact with the blastoderm, which allows the primitive streak to form. This happens in avian gastrulation, a process by which developing cells in an avian embryo move relative to one another in order to form the three germ layers (endoderm, mesoderm, and ectoderm).

Koller' sickle, unedited

 * pre-editing, just in case we want to switch back

In avian gastrulation, Koller's sickle is a local thickening of cells at the posterior edge of the area pellucida, specifically the upper layer, which is called the epiblast. The thickening of the epiblast acts as a margin separating sheets of cells from posterior margin of avian blastoderms from hypoblasts and area opaca endoderm. The blastoderm is a single layer of cells, and the hypoblast and area opaca endoderm cells lie directly below the blastoderm. Koller's sickle arises from the midpoint, between the hypoblast cells and the area opaca endoderm. As blastoderm cells migrate anteriorly and push primary hypoblast cells, forming a secondary hypoblast known as the endoblast, Koller's sickle is responsible for preventing the hypoblast cells and the area opaca cells from making contact with the blastoderm, which allows the primitive streak to form. This happens in avian gastrulation, a process by which developing cells in an avian embryo move relative to one another in order to form the three germ layers (endoderm, mesoderm, and ectoderm).

Formation of the primitive streak
Primitive streak is induced by the posterior marginal zone (PMZ) of Koller's sickle, which can also induce Hensen's node. Thus, the PMZ acts as an organizer. Cells in marginal zones of the embryo, like the PMZ, are key to development and cell fate determination in chick embryos.

Avian gastrulation occurs as cells move though the primitive streak. Hence, primitive streak is analogous to the blastopore lip in amphibian gastrulation. The primitive streak develops from Koller’s sickle and the epiblast of the avian embryo. As the cells of Koller’s sickle migrate during gastrulation, they form different portions of the primitive streak. The anterior cells of Koller’s sickle become the anterior region of the primitive streak, known as Hensen's node. Similarly, the posterior cells of Koller’s sickle form the posterior region of the primitive streak. This differential movement is due to expression of different mesodermal marker genes among the cells located in different areas of Koller’s sickle. Chordin is expressed in cells of the anterior streak, while Wnt8c is expressed in cells of the posterior streak. The movement is coordinated by a Wnt signaling pathway which is activated by fibroblast growth factors from the hypoblast.

The primitive streak is key in the development of the major body axes. The primitive groove forms as a depression in the primitive streak as it is developing, and allows a space for migrating cells to move into the deeper layers of the embryo. Cells migrate by entering through the dorsal side and moving toward the ventral side of the avian embryo, separating the left and right sections of the embryo. The primitive pit in Hensen’s node, at the anterior end of the primitive streak, allows cells to enter which will form the notochord and prechordal plate. Cells that move through the center of the streak will become the heart and kidneys. The lateral plate and the extraembryonic mesoderm arise from the cells that enter at the posterior end of the primitive streak. Epiblast cells near the primitive streak form the neural plate and other dorsal structures, while the epiblast cells far from the streak become epidermis.

Role of the posterior marginal zone, unedited
The posterior marginal zone (PMZ) of Koller's sickle can induce a primitive streak and Hensen's node, acting as an organizer. Cells in marginal zones of the embryo, like the PMZ, are key to development and cell fate determination in chick embryos. The PMZ is a region in between the Koller's sickle and the area opaca. Cells that are derived from Koller's sickle migrate beneath the surface of the PMZ. Cells combine to form sheets and grow anteriorly from Koller's sickle to generate the complete hypoblast layer of the chick blastoderm by combining with hypoblast islands.
 * pre-editing, just in case we want to switch back

Formation of the primitive streak, unedited
Avian gastrulation occurs as cells move though the primitive streak. The primitive streak develops from Koller’s sickle and the epiblast of the avian embryo. As the cells of Koller’s sickle migrate during gastrulation, they form different portions of the primitive streak. The anterior cells of Koller’s sickle become the anterior region of the primitive streak, known as Hensen's node. Similarly, the posterior cells of Koller’s sickle form the posterior region of the primitive streak. This differential movement is due to expression of different mesodermal marker genes among the cells located in different areas of Koller’s sickle. Chordin is expressed in cells of the anterior streak, while Wnt8c is expressed in cells of the posterior streak. The movement is coordinated by a Wnt signaling pathway which is activated by fibroblast growth factors from the hypoblast.
 * pre-editing, just in case we want to switch back

The primitive streak is key in the development of the major body axes. The primitive groove forms as a depression in the primitive streak as it is developing, and allows a space for migrating cells to move into the deeper layers of the embryo. Cells migrate by entering through the dorsal side and moving toward the ventral side of the avian embryo, separating the left and right sections of the embryo. The primitive pit in Hensen’s node, at the anterior end of the primitive streak, allows cells to enter which will form the notochord and prechordal plate. Cells that move through the center of the streak will become the heart and kidneys. The lateral plate and the extraembryonic mesoderm arise from the cells that enter at the posterior end of the primitive streak. Epiblast cells near the primitive streak form the neural plate and other dorsal structures, while the epiblast cells far from the streak become epidermis.