Diisobutyl phthalate

Diisobutyl phthalate (DIBP) is a phthalate ester having the structural formula |C6H4(COOCH2CH(CH3)2)2. It is formed by the esterification of isobutanol and phthalic anhydride. This and other phthalates are used as plasticizers due to their flexibility and durability. They are found in many industrial and personal products, such as lacquers, nail polish and cosmetics. DIBP can be absorbed via oral ingestion and dermal exposure. When it comes to excretion, DIBP is first converted into the hydrolytic monoester monoisobutyl phthalate (MIBP). The primary excretory route is urine, with biliary excretion being noted in minor amounts. DIBP has lower density and freezing point than the related compound dibutyl phthalate (DBP). Phthalates, including DIBP, were first introduced in the 1920s to make plastics more flexible, transparent and long lived. They increased their popularity in 1931 when polyvinylchloride (PVC) became commercially available.

Date Action References December 14, 2005 The European Union restricted phthalates from several children's toys. July 4, 2017 Included in the candidate list referred to as substances toxic for reproduction. November 23, 2021 DIBP is declared as an endocrine disrupting chemical. August 11, 2021 The European Parliament eliminates DIBP and other phthalates from sanitary products.

It is used as a plasticizer additive in a range of plastic and rubber materials. DIBP has been found to be relatively non toxic, but high levels of exposure to the compound may cause irritation to the eyes, skin and respiratory tract. DIBP has been detected in various environmental matrices, such as air, water, and sediment. DIBP is known to bioaccumulate in certain aquatic species

DIBP is synthesized by a double nucleophilic acyl substitution reaction between phthalic anhydride and isobutanol, using various acids as a catalyst, such as sulfuric acid, sulfonated graphene, or iron(III) chloride. Water is a byproduct. Using sulfuric acid, the yield is 61% yield.

Sulfonated graphene is a heterogeneous catalyst that has several advantages over traditional liquid acids like sulfuric acid. Sulfonated graphene can be easily separated from the reaction mixture by filtration and can be reused multiple times without reduction in activity. Furthermore, sulfonated graphene is environmentally friendly, as it does not produce hazardous waste materials that are typically generated during the use of traditional liquid acid catalysts. This method has a 95% yield. The Lewis acid catalysis process can be run at lower temperatures (50 100 °C), and gives a yield of 86%. It is insoluble in water but soluble in many organic solvents. DIBP can be sold as a pure substance or as a component of mixtures with other phthalate plasticizers or chemicals. Examples are dioctyl phthalate (DOP), diisononyl phthalate (DINP), or bis(2 ethylhexyl) phthalate (DEHP). It may be used as a component in formulations of several products including adhesives, paints, coatings and lubricants. This can lead to the breakdown and the eventual degradation of DIBP in the soil and water supply
Photodegradation: DIBP can undergo photodegradation by exposure to the sunlight. This can lead to the formation of several degradation products, including phthalic acid, isobutyraldehyde, and other aldehydes. Biodegradation: DIBP can be degraded by microorganisms in soil and in the water. This can transform it into other compounds such as phthalic acid and various isobutyl alcohol derivatives. Sorption: DIBP can adsorb or sorb onto soil and sediment particles, which can limit its mobility and availability for biological or chemical degradations and reactions. Oxidation: DIBP can be oxidized in the presence of ozone or other reactive oxygen species. The formation of various oxidation products, including aldehydes, ketones, and carboxylic acids can be expected

These reactions can impact the persistence, bioaccumulation, and toxicity in the environment and may have implications for human and ecosystem health.

The effects of DiBP exposure are mainly realized through its activation of peroxisome proliferator activated receptor gamma (PPARγ). PPARs are ligand activated nuclear transcription factors, the family consists of PPARα, PPARβ/δ and PPARγ. There are two isoforms of PPARγ, PPARγ2 is mainly present on cells in adipose tissue, whereas PPARγ1 is found on multiple cells like those in the gut, brain, blood vessels, and some immune and inflammatory cells. Transcriptional regulation through PPARs requires the formation of a heterodimer with retinoid X receptor (RXR). Upon activation by DiBP this PPARγ/RXR heterodimer binds to a DNA sequence called the PPAR response element (PPRE). Binding of the transcription factor to this response element can result in either up or down regulation of genes. PPARγ is involved in lipid metabolism and storage as well as glucose metabolism through improving insulin sensitivity, so binding of DiBP leads to altered leptin and insulin levels. DiBP also leads to a down regulation of proteins involved in steroid production, resulting in higher levels of androgenic hormones. Prolactin (PLR) on the other hand is up regulated as a result of DiBP exposure. High PLR concentrations as a result of phthalate exposure has been linked to reduced sperm concentrations in both adult men and zebra fish. The main metabolite of DiBP is mono isobutyl phthalate (MiBP), which makes up 70% of the excretion products. MiBP can be oxidized to either 2OH mono isobutyl phthalate (2OH MiBP) or 3OH mono isobutyl phthalate (3OH MiBP), which make up 20% and 1% of the excretion products respectively. These reactions are likely catalyzed by cytochrome P450 in the liver. The ratio between MiBP and the oxidized metabolites changes depending on the amount of time that has passed since exposure.

There's insufficient data to determine if DIBP is associated with acute dermal or inhalation toxicity, eye or dermal irritation, or sensitization. There is evidence on DIBP being a subchronic toxicant. Exposure to the compound can induce changes in body weight, liver weight, reproductive effects, and developmental effects like testicular weight, spermatogenesis, fetal body weight, anogenital distance in male and female rats, and testicular testosterone production, among others. Biomonitoring studies show that exposures to DIBP have grown recently, presumably as a result of DIBPs use as a substitute for other phthalates such as dibutyl phthalate (DBP) in plastics. In the United States, for instance, the prevalence of MIBP detection in urine has risen from 72% of the general population in 2001–2002 to 96% in 2009–2010, according to data from the National Health and Nutrition Examination Survey (NHANES).