Phthalates substitutes

Abstract We have reviewed the human exposure to selected emerging organic contaminants, such new brominated flame retardants, organophosphate flame retardants, phthalate substitutes, triclosan, synthetic musks, bisphenol-A, perchlorate, and polycyclic siloxanes. Levels of these emerging contaminants in matrices relevant for human exposure (air, dust, food, water, etc.) and in human matrices (blood, urine, or tissues) have been reviewed, together with some of the relevant health effects reported recently. 

Some studies showed already that the levels of phthalate substitute s metabolites measured in human s urine are usually lower when compared to DEHP metabolites (Table 7) [105, 135]. However, such comparison should be carefully addressed since it was shown through rats exposure to such plasticizers that a considerable portion (about 50%) of the orally dosed DINP is excreted via the feces while it is known that DEHP is mainly extracted in humans via urine [105, 141]. 

Table 7 Levels (I median/range concentrations expressed in pg/L of sample II median/range creatinine adjusted concentrations expressed in pg/g) of phthalates, substitutes, and their metabolites from human fluids samples...

It is pertinent that phthalate substitution for certain toys and child care items is still in progress because further studies concerning toxicological and technical aspects of their substitutes are still required to confirm selection of substitutes. This is still a big issue now and it is expected that more information will be available in the future. 

Phthalate substitutes can also leach out of plastics, and their toxicity to human consumers has not as yet been comprehensively studied. Once the functional equivalence of a substitute plasticizer is established, exhaustive studies need to be imdertaken to unambiguously validate their safety to health and environment. 

Phthalic anhydride and diethyl phthalate are easily converted with hydrazine into 4-hydroxyphthalazin-l(2/f)-one. Its substituted derivatives have been prepared using substituted hydrazines, substituted phthalic anhydrides, or diesters or disodium salts of substituted phthalic acids (Scheme 81). However, condensation of phenylhydrazine with phthalic anhydride gives only a small amount of the corresponding phthalazine, the main product being 2-anilinophthalimide. This can be rearranged in the presence of base into the phthalazine derivative. For the preparation of 2,3-disubstituted derivatives, 1,2-disub-stituted hydrazines are reacted with the appropriate phthalic anhydrides or phthaloyl chlorides. Derivatives of 4-amino- or 4-hydrazino-phthalazin-l(2iT)-one have been prepared either from the corresponding monothiophthalimide and 3-aminoisoindolin-3-one (1S4) or from ethyl 2-cyanobenzoate (155) and hydrazine hydrate (Scheme 82). Similarly,... 

The main features of PC are low cost, need for small sample amount, high level of resolution, ease of detection and quantitation, simplicity of apparatus and use, difficult reproducibility (because of variation in fibres) and susceptibility to chemical attack. Identification of the separated components is facilitated by the reproducible Rj values. Detection methods in PC have been reviewed [368]. Fluorescence has been used for many years as a means of locating the components of a mixture separated by PC or TLC. However, also ATR-IR and SERS are useful. Preparative PC is unsuitable for trace analysis because filter paper inevitably contains contaminants (e.g. phthalate esters, plasticisers) [369]. For that purpose an acceptable substitute is glass-fibre paper [28]. 

Furthermore, the EU regularly produces and regularly updates the list of substances of high concern, i.e. the SVHC list. The identification of a substance as a SVHC and its inclusion in the candidate list is the first step of the authorization procedure. The European Chemical Agency in Helsinki identifies from the candidate list priority substances to be included in Annex XIV of REACH (the authorisation list). The substances on the candidate list will most probably be liable to stricter regulation in the future (authorisation/banning) which will stimulate the substitution of these chemicals. Currently in June 2012, there are 84 substances included in the candidate list. Examples of chemicals on the candidate list which may be relevant for the leather industry are phenolphthalein, boric acid, cobalt dichloride, dichromate (although not used by leather industry), phthalates (DEHP, DBP and BBP), acrylamide and short-chain chlorinated paraffins. 

Atmospheric ozone has also been reported as causing fading of certain dyes in some countries [425,426] diallyl phthalate (10.182) used as a carrier in the dyeing of cellulose triacetate fibres, is said to be an effective ozone inhibitor [427]. Nylon, especially when dyed with certain amino-substituted anthraquinone blue acid dyes, can also be susceptible to ozone fading [428,429]. Selection of ozone-resistant dyes is obviously the best counteractive measure, although hindered phenols (10.161) and hindered amines (10.162) are said to provide some protection. 

The hemidecarboxylation of sodium phthaiate on reaction with mercuric acetate in boiling water [Eq. (82), X = H] (90) was the first reported thermal decarboxylation. The reaction has been observed for a number of arenes with two adjacent carboxylate groups (1-4,91) and has been named the Pesci reaction (91). Studies of 3-substituted sodium phthalates or of preformed mercuric 3-substituted phthalates have shown that the sterically hindered carboxyl group (the 2-carboxyl) is preferentially eliminated whether X is electron-donating or electron-withdrawing [Eq. (82), X = Me (91), Cl, N02 (91,93), Br (93), or C02H (94)]. A similar conclusion was drawn from the decomposition of mercuric 1,2-naph-thalenedicarboxylate and 3,4-phenanthrenedicarboxylate (91). 

Pentacene is a useful compound in materials science, in particular for use in solar batteries, superconductors, and laser emission materials, etc. Unfortunately, however, pentacene is not soluble in organic solvents. As shown in Eq. 2.57, a combination of the aforementioned benzene formation reaction and alkynylation of phthalate leads to alkyl-substituted pentacenes, which are very soluble in various organic solvents... 

It is briefly reported that the European Commission will issue a White Paper on PVC within the next couple of months. The Paper will probably be a mix of both legislation and voluntary commitments. A Green Paper on PVC was adopted by the EC in July 2000. This raised six issues to be addressed substitution, production process, cadmium stabilisers, lead stabilisers, phthalates and waste management. 

Aliphatic hydrocarbons, triazine, substituted urea type and phenoxyacetic acid types of herbicides, Fluazifop and Fluazifop-butyl herbicides, ethylene diamine tetracetic acid salts in soil, aliphatic and polyaromatic hydrocarbons, phthalate esters, various organosulphur compounds, triazine herbicides, optical whiteners, mixtures of organic compounds and organotin compounds in non-saline sediments, aromatic hydrocarbons, humic and fulvic acids and mixtures of organic compounds in saline sediments and non-ionic surfactants and cobalamin in sludges. 

Chemical Substitution Phthalates are used to provide flexibility to the polymer backing. The use of alternative plasticizers represents the most direct method of substitution. In some cases this choice may have little impact on production techniques, and so be the most economically favourable option in immediate terms. 

Material Substitution Replacement of the entire backing with a different material, e.g. a different plastic polymer that does not require phthalate plasticizers removes the need for these chemicals. Other hazards associated with PVC are also then avoided, with potential economic benefits in the medium to long-term. An innovative use of this approach is demonstrated in Annex I (6). 

The influence of temperature on the ortho effect has been evaluated in the alkaline hydrolysis in aqueous DMSO solutions of ortho-, meta- and para-substituted phenyl benzoates (26). The alcoholysis of phthalic anhydride (27) to monoalkyl phthalates (28) occurs through an A-2 mechanism via rate-determining attack of the alcohol on a carbonyl carbon of the anhydride (Scheme 4). Evidence adduced for this proposal included highly negative A 5 values and a p value of 4-2.1. In the same study, titanium tetra-n-butoxide and tri-n-butyltin ethanoxide were shown to act as effective catalysts of the half-ester formation from (27), the mechanism involving alkoxy ligand exchange at the metal as an initial step. ... 

To evaluate human exposure to phthalates and their substitutes, the main approaches investigate either the levels of chemicals in matrices relevant for human exposure (indoor air, dust, food and packages, etc.) or the levels of parent and metabolite compounds in human samples (serum, urine, or breast milk). An overview of phthalate and nonphthalate plasticizers together with their metabolites commonly reported in literature is presented in Table 5. The half-lives for the most of these compounds are already established and therefore, by evaluating the levels of their metabolites in human urine, the levels of their parent compounds may be... 

Table 6 Literature survey on levels of most commonly used phthalates and their substitutes in house dust (median concentrations and in brackets P95 concentrations, results expressed in pg/g) and in indoor air samples (median concentrations, results expressed in ng/m )... 

Phthalates in general, as well as their substitutes, became large volume workplace chemicals and further ubiquitous environmental contaminants. Their impact on organism s health was relatively intense tested through several exposure experiments ([142, 305]). However, it seems that in general they display low toxicity [305], their effects being recorded only for high dose exposure levels... 

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