Final Amended Report on the Safety Assessment of Methylparaben, Ethylparaben, Propylparaben, Isopropylparaben, Butylparaben, Isobutylparaben, and Benzylparaben as used in Cosmetic Products

Abstract

Coal Tar is a semisolid by-product obtained in the destructive distillation of bituminous coal, which functions in cosmetic products as a cosmetic biocide and denaturant--antidandruff agent is also listed as a function, but this is considered an over-the-counter (OTC) drug use. Coal Tar is a nearly black, viscous liquid, heavier than water, with a naphthalene-like odor and a sharp burning taste, produced in cooking ovens as a by-product in the manufacture of coke. Crude Coal Tar is composed of 48% hydrocarbons, 42% carbon, and 10% water. In 2002, Coal Tar was reported to the Food and Drug Administration (FDA) to be used in four formulations, all of which appear to be OTC drug products. Coal Tar is monographed by the FDA as Category I (safe and effective) OTC drug ingredient for use in the treatment of dandruff, seborrhoea, and psoriasis. Coal Tar is absorbed through the skin of animals and humans and is systemically distributed. In short-term studies, mice fed a diet containing Coal Tar found it unpalatable, but no adverse effects were reported other than weight loss; rats injected with Coal Tar experienced malaise in one study and decreased water intake and increased liver weights in another; rabbits injected with Coal Tar residue experienced eating avoidance, respiratory difficulty, sneezing, and weight loss. In a subchronic neurotoxicity study using mice, a mixture of phenols, cresols, and xylenols at concentrations approximately equal to those expected in Coal Tar extracts produced regionally selective effects, with a rank order of corpus striatum > cerebellum > cerebral cortex. Coal Tar applied to the backs of guinea pigs increases epidermal thickness. Painting female rabbits with tar decreases the absolute and relative weights of the ovaries and decreased the number of interstitial cells in the ovary. Four therapeutic Coal Tar preparations used in the treatment of psoriasis were mutagenic in the Ames assay. Urine and blood from patients treated with Coal Tar were genotoxic in bacterial assays. Coal Tar was genotoxic in a mammalian genotoxicity assay and induced DNA adducts in various tissue types. Chronic exposure of mice to Coal Tar significantly decreased survival and liver neoplasms were seen in a significant dose-related trend; in other studies using mice lung tumors and perianal skin cancers were found. Coal Tar was comedogenic in three small clinical studies. Folliculitis is associated with the prolonged use of some tars. Several published reports describe cases of contact sensitivity to Coal Tar. Polycyclic aromatic hydrocarbons, which make up Coal Tar, are photosensitizers and cause phototoxicity by an oxygen-dependent mechanism. A retrospective study of the reproductive toxicity of Coal Tar in humans compared exposed women to controls and found little difference in spontaneous abortion and congenital disorders. Cancer epidemiology studies of patients who have received Coal Tar therapy of one form or other have failed to link treatment with an increase in the risk of cancer. Although the Cosmetic In...

Prenatal Exposure to Select Phthalates and Phenols and Associations with Fetal and Placental Weight among Male Births in the EDEN Cohort (France)

“…2015). Parabens are used as preservatives in cosmetics, personal care products, food, and some pharmaceuticals (Andersen 2008). Benzophenone-3 is an ultraviolet light filter used in sunscreen, clear plastic packaging, and other products to prevent damage to color and scent (e.g., soap, perfumes) (IARC 2013).…”

Skin Sensitization to Fluorescein Isothiocyanate Is Enhanced by Butyl Paraben in a Mouse Model

“…This is supported by the lack of sensitization in signal transducer and activator of transcription 6 (STAT6)-deficient mice, which have a defect in Th2 differentiation. 17) However, diisopropyl adipate (DIPA; an alternative plasticizer) was found to induce only marginal IL-4 but abundant IFN-γ production by draining lymph nodes in BALB/c mice. 12) In the present study, DBP was confirmed to augment both IL-4 and IFN-γ production (Fig.…”

Neomycin, polymyxin B, and dexamethasone allergic reactions following periocular surgery

“…The non-antibiotic components of NPD ointment have been shown to cause allergic hypersensitivity reactions, but as previously discussed, the concentrations required for this are 100 to 1000-fold greater to what is found in the NPD compound studied [4, 6]. Similarly, dexamethasone has been associated with a very low rate of allergic contact skin reactions [5].…”

“…Each of the agents in this combined steroid/anti-infective ophthalmic ointment has been individually investigated for the incidence of topical allergic contact dermatitis—a type IV hypersensitivity reaction [4, 5]. Polymyxin B has a low sensitization rate, and there is not sufficient evidence to discourage its use because subsequent topical exposure to the antigen is unlikely to cause an allergic contact dermatitis [6–8].…”

“…Parabens can trigger irritation and allergic hypersensitivity reactions, but the concentrations required (5–12%) are significantly higher than what is used in clinical practice [4]. Few studies examining parabens and ocular allergy are available in the literature.…”