Phthalates toxicity

EPA. 1993a. Di-w-octyl phthalate toxic chemical release reporting community right-to-know. U.S. Environmental Protection Agency. Federal Register 58(8) 4133-4137. 

In a neonatal rat model used to assess di(2-ethylhexyl) phthalate toxicity following intravenous administration, groups of 12 neonates, two to four days of age, were injected intravenously with 30.8, 91.7 or 164.8 mg/kg bw di(2-ethylhexyl)... 

Swenberg JA, Thurman RG University of North Carolina Chapel Hill, North Carolina Lipid metabolism and phthalate toxicity interactions NIEHS... 

No methods which would interfere with mechanism of di- -butyl phthalate toxic were identified. 

The available toxicokinetic data did not evaluate the potential differences between adults and children, although there is some evidence that there are age-related differences in the activity of at least one enzyme, UDP-glucoronsyltransferase, that is involved in the metabolism of di- -butyl phthalate. Toxicokinetic studies examining how aging can influence the absorption, distribution, and excretion of di- -butyl phthalate would be useful in assessing children s susceptibility to di- -butyl phthalate toxicity. The mechanism of action for a number of toxic effects have not been elucidated. There are no data to determine whether there are age-specific biomarkers of exposure or effects or any interactions with other chemicals that would be specific for children. There is very little available information on methods for reducing di- -butyl phthalate toxic effects or body burdens it is likely that research in adults would also be applicable to children. 

Methyl Ethyl Ketone Peroxide in Dimethyl Phthalate (4TT3)), National Toxicology Program, Toxicity Report Series Number 18, NIH Pubhcation 93-3341, United States Department of Health and Human Services, Washington D.C., Eeb. 1993. 

Chronic Toxicity. The effects of repeated oral exposure to phthalates for periods ranging from a few days to 2 years have been studied in a number of animal species including rats, mice, hamsters, guinea pigs, ferrets, and dogs (37). 

The reproductive toxicity of some phthalate esters has been reviewed by the Commission of the European Communities (45). This review concludes that testicular atrophy is the most sensitive indicator of reproductive impairment and that the rat is the most sensitive species. 

Atmospheric Toxicity. The only known atmospheric toxicity effect of phthalates is the phytotoxicity arising from the use of DBP plasticized glazing bars in greenhouses. However, the higher phthalates such as DEHP are not phytotoxic. General atmospheric concentrations of phthalates are extremely low and it is concluded that they pose no risk to plants or animals. 

Aquatic Toxicity. The standard tests to measure the effect of substances on the aquatic environment are designed to deal with those that are reasonably soluble ia water. Unfortunately this is a disadvantage for the primary phthalates because they have a very low water solubiUty (ca 50 p.g/L) and this can lead to erroneous test results. The most common problem is seen ia toxicity tests on daphnia where the poorly water-soluble substance forms a thin film on the water surface within which the daphnia become entrapped and die. These deaths are clearly not due to the toxicity of the substance but due to unsuitable test design. 

The majority of studies on the acute and chronic toxicity of phthalates to aquatic organisms show no toxic effects at concentrations 200—1000 times the water solubiUty. However, there are some studies iadicatiag higher toxicity which are beheved to be due to the flotation and entrapment effects outlined above. 

Sediment Toxicity. Because of their low solubiUty ia water and lipophilic nature, phthalates tend to be found ia sediments. Unfortunately httle work has previously been carried out on the toxicity of phthalates to sediment dwelling organisms. Eor this reason ECPI has commissioned some sediment toxicity studies designed to measure the effect of DEHP and DIDP ia a natural river sediment on the emergence of the larvae of the midge, Chironomus riparius. 

Many other compounds are presendy in use a 1993 database search showed 27 active ingredients in 212 products registered by the U.S. EPA for human use as repellents or feeding depressants, including octyl bicycloheptene dicarboxamide (A/-2-ethylhexylbicyclo[2.2.1]-5-hepten-2,3-dicarboxamide), dipropyl isocinchomeronate (2,5-pyridine dicarboxyhc acid, dipropyl ester), dimethyl phthalate, oil of citroneUa, cedarwood oil, pyrethrins, and pine tar oil (2). Repellent—toxicant or biting depressant systems are available which are reasonably comfortable for the user and can protect completely against a number of pests for an extended period of time (2). 

Most carrier-active compounds ate based on aromatic chemicals with characteristic odor. An exception is the phthalate esters, which are often preferred when ambient odor is objectionable or residual odor on the fabric caimot be tolerated. The toxicity of carrier-active compounds and of their ultimate compositions varies with the chemical or chemicals involved. The environment surrounding the dyeing equipment where carriers are used should always be weU-ventilated, and operators should wear protective clothing (eg, mbber gloves, aprons, and safety glasses or face shields, and possibly an appropriate respirator). Specific handling information can be obtained from the suppHer or manufacturer. 

The phthalate esters are one of the most widely used classes of organic esters, and fortunately they exhibit low toxicity (82). Because of the ubiquitous nature of phthalates, many iavestigations have been conducted to determine their toxicides to marine life as well as ia mammals (83—85). Generally, phthalates are not absorbed through the skin and are not very potent when inhaled. The phthalates become less toxic as the alcohol group increases in molecular weight. For example, dimethyl phthalate has an oral LD q (mouse) of 7.2 g/kg, whereas di(2-ethylhexyl) phthalate shows an oral LD q (rat) of greater than 26 g/kg. 

In addition to their endocrine disrupting properties, it must be appreciated that many of the chemicals in question possess more general toxic properties, which may be potentiated by metabolism by the organism. Several PAHs, PCBs and PCDDs are carcinogenic, while certain phthalate esters can enhance the excretion of zinc, potentially leading to zinc deficiency. Zinc, an essential element, plays a vital role in spermatogenesis and mature T-cell production. Deficiency may result in abnormalities of the male reproductive system, depletion of spermatogenesis and suppression of the immune system. 

The mechanism of this reaction has been studied by several groups [133,174-177]. The consensus is that interaction of ester with the phenolic resole leads to a quinone methide at relatively low temperature. The quinone methide then reacts rapidly leading to cure. Scheme 11 shows the mechanism that we believe is operative. This mechanism is also supported by the work of Lemon, Murray, and Conner. It is challenged by Pizzi et al. Murray has made the most complete study available in the literature [133]. Ester accelerators include cyclic esters (such as y-butyrolactone and propylene carbonate), aliphatic esters (especially methyl formate and triacetin), aromatic esters (phthalates) and phenolic-resin esters [178]. Carbamates give analogous results but may raise toxicity concerns not usually seen with esters. 

The chemical industry uses esters for a variety of purposes. Ethyl acetate, for instance, is a commonly used solvent, and dialkyl phthalates are used as plasticizers to keep polymers from becoming brittle. You may be aware that there is current concern about possible toxicity of phthalates at high concentrations, although a recent assessment by the U.S. Food and Drug Administration found the risk to be minimal for most people, with the possible exception of male infants. 

Persistent activation of PPARa can induce the development of hepatocellular carcinoma in susceptible rodent species by a nongenotoxic mechanism, i.e., one that does not involve direct DNA damage by peroxisome proliferator chemicals or their metabolites. This hepatocarcinogenic response is abolished in mice deficient in PPARa, underscoring the central role of PPARa, as opposed to that of two other mammalian PPAR forms (PPARy and PPAR5), in peroxisome proliferator chemical-induced hepatocarcinogenesis. Other toxic responses, such as kidney and testicular toxicities caused by exposure to certain phthalate... 

Review of the toxicity of the esters of o-phthalic acid (phthalate esters). 

Narotsky MG, Weller EA, Chinchilli VM, et al. 1995. Nonadditive developmental toxicity in mixtures of trichloroethylene, di(2-ethylhexyl) phthalate, and heptachlor in a 5 x 5 x 5 design. Fund Appl Toxicol 27 203-216. 

In the biocatalytic system, a second organic phase consisting of bis(2-ethyUiexyl)phthalate and containing the substrate is added at a phase ratio of 1 1. This procedure enables in situ product extraction and protects the microbial cells from toxic effects of the substrate and... 

Toxic Pollutants (gg/L) Toxic organics Bis (2-ethylhexyl) phthalate 4/4 BDL-890 BDL 240... 

Painting wastewater generally consists of quench water. Wastewater from this operation is generally less toxic than wastewater from the other general operations normally, only the following pollutants are expected to exceed 10 pg/L oil and grease, fluorides, TSS, iron, zinc, bis(2-ethyl-hexyl) phthalate, and diethyl phthalate. 

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