(Chemical Abstract Service Registry Number 5466-77-3; IUPAC Name 2-Ethylhexyl Methoxycinnamate; 2-Ethylhexyl 4-Methoxycinnamate; p-Methoxycinnamic Acid, 2-Ethylhexyl Ester; 3-(4-Methoxyphenyl)-2-Propenoic Acid, 2-Ethylhexyl Ester; Octyl Methoxycinnamate; 2-Propenoic Acid, 3-(4-Methoxyphenyl)-, 2-Ethylhexyl Ester.
For humans and mammals, the most common pathological reaction to Octinoxate is contact dermatitis and photoallergic reactions (31-38).
Octinoxate on top of the skin or in the epidermal layer can be degraded by sunlight (called photodegradation), and those breakdown products can be especially toxic (39).
Once in the body, Octinoxate can cause toxicity to a number of different organ systems. Developing fetuses, babies, pre-adolescents, and even the pregnant mother are especially susceptible. In pregnant rats exposed to Octinoxate, there was a significant decrease in thyroid hormone levels (Thyroxine) (51). Young male rats whose mothers were exposed to octinoxate had smaller testicals and lower semen quality, and a dose-dependent reduction in testosterone levels – meaning the more Octinoxate the mother was exposed to, the lower the level of testosterone in the offspring male. Young female rats from the same Octinoxate-exposed mothers exhibited reduced motor activity levels (51). Like Oxybenzone, Octinoxate can impair both neurological and reproductive abilities (52-57, 73).
Another study that focused on two generations of rats exposed to Octinoxate also exhibited liver/blood disease, occurrence of ulcers in the stomach, and a higher risk to miscarriage (60). Furthermore, the off-spring had reduced organ weights, increased difficulty gaining weight during breast feeding, and a significant delay in sexual maturation (60). It is by reasonable argument that Octinoxate should be classified as a reproductive endocrine disruptor (58-59). A number of studies demonstrate that Octinoxate is a multi-system or multi-axis endocrine disruptor – meaning it can disrupt more than one type of endocrine system. Octinoxate can adversely affect estrogen receptors, androgen receptors, progesterone receptors, and thyroid hormone receptors (40-43, 48, 75, 80). This mimicking of estrogen by Octinoxate was also shown to be able to adversely impact the immune system (67).
There have been a number of strong scientific studies on the impact of Octinoxate to the mammalian Thyroid gland and its function (53, 61). Octinoxate affects both adult and juvenile mammals.
Danish scientists publicized in 2016 the impact of 29 different UV filters on sperm function and viability. Octinoxate was one of the UV filters that had an adverse effect on sperm function (85).
Genotoxicity of a chemical is a critical factor for its regulation and use in consumer products. The trend in the scientific literature indicates that Octinoxate is a genotoxin – meaning it damages DNA and the genetic material, and can give rise to genetic mutations, further resulting in the potential manifestation of reduced reproductive viability, adverse embryonic development, and cancer. One study provided data, using the Ames Test, that Octinoxate was mutagenic, as well as in a Fruit Fly genetic test (76). The authors, in their paper, stated that “A trace contaminant may be implicated because many samples were obtained from several sources and the results were batch-related.” This begs the question of why this study was allowed to be published by the journal, or were such statements in the paper a result of pressure from outside forces on the Journal’s editorial staff. Other studies on Octinoxate’s genotoxicity using bacterial models demonstrated positive mutagenicity (66, 77, 78). One relatively recent study showed that Octinoxate does prevent one type of DNA damage by UV radiation, but it does not prevent DNA damage caused by oxidative stress (68).
There have been some in vitro cell culture studies, showing the toxicity of Octinoxate to neuroblastoma cells, liver stem cells, and human white blood cells (69, 70). Some of these cell types exhibited a DNA-damage gene response exhibited, further arguing that Octinoxate is genotoxic (70, 72).
By 1994, over a million pounds of Octinoxate is manufactured each year (10). If historical evidence indicates the propensity of Octinoxate to be genotoxic, better studies by independent laboratories characterizing its genotoxicity and threat to human and ecological receptors is a necessity.
A “sister” compound of Octinoxate, called Cinoxate, supports this call for further investigation. Cinoxate was found to cause an increase in chromosome aberrations (type of genotoxicity) in mammalian cells using an industry-accepted method (79).
Carcinogenicity arises out of the interaction between genetic damage and cellular/tissue environmental instability. A recent paper by Alamer and Darbre shows that Octinoxate, Oxybenzone, Benzophenone-1 (breakdown product of oxybenzone), homosalate, and 4-MB-Camphor increased the metastatic behavior of breast cancer cells (80).
Toxicity to Wildlife – Most of the research has focused on the toxicity of Octinoxate to fish. Exposure to non-lethal concentrations radically alters the activation of genes in fish, altering the expression of over 1130 different gene transcripts (47). Many of the altered genes play a role in hormonal regulation, including enzymes and proteins regulating estrogen and testosterone, as well as DNA damage and lipid synthesis.
At least three other studies in fish demonstrate that Octinoxate is an endocrine disruptor and causing reproductive disease at relevant environmental concentrations (44, 48-50). A team of Dutch scientists were one of the first to show that Octinoxate induced estrogenic disruption in fish (Zebrafish) (48). Scientists from Japan showed that male fish (Medaka) exposed to Octinoxate caused a reproductive endocrine disruption by having these male fish produce egg proteins (49). Scientists in Switzerland confirmed these results using a different species of fish (fathead minnows); and that Octinoxate impacted multiple hormonal systems (50).
A team of Korean scientists did some amazing work showing that exposure to Octinoxate during embryonic development results in organ and body axis deformities in Zebrafish (71). Octinoxate exposure had a statistically significant effect to induce liver defects. In this same study, a mixture of Oxybenzone and Octinoxate induced synergistic deformities in embryonic development of Zebrafish.
For invertebrates, such as a crustacean species of Daphnids, the same authors demonstrated that exposure of Octinoxate caused immobilization of Daphnia, as well as deformities (71, 45). These results were consistent with an earlier study done by German Scientists on Octinoxate toxicity and Daphnia (83), which saw growth inhibition of Octinoxate at 240 parts per billion and as low as >40 parts per billion.
Studies on other invertebrates, such as the larvae of the aquatic midge, Chironomus riparius, indicated that Octinoxate induced the Stress Protein response in midges, as well as induced the overexpression of an insect hormone receptor (ecdysone receptor), indicating that it acts as an endocrine disruptor to insects (45).
One of the best scientific papers to examine the ecotoxicity of Octinoxate on the different trophic levels of a marine ecosystem was the work done by group of Spanish scientists (81). In this study, they looked at the toxicity of Octinoxate to an algae, a mussel, a sea urchin, and a shrimp (carnivore). They saw toxic effects of Octinoxate of these four organisms as low as 52 parts per billion and concluded that Octinoxate (and Oxybenzone) “could pose significant risks to marine aquatic ecosystem.”
Future work from the Haereticus laboratory will be demonstrating the toxicity of Octinoxate to coral, including the inducing corals to undergo bleaching. Coral exposed to pollutants that causes them to bleach, makes these corals more susceptible when a climate event occurs, such as an El Nino-induced mass bleaching event.
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