antioxidants in food packaging: risk factor?the end products are the potentially toxic chemicals,...

Biochem. SOC. Symp. 6 I , 235-246 Printed in Great Britain

Antioxidants in food packaging: a risk factor? Gerald Scott

Department of Chemical Engineering and Applied Chemistry, Aston University, Birmingham B4 7ET, U.K.

Abstract

It is current practice to test all new additives for packaging polymers for toxicity before permitting them to be used in food contact applications. However, many antioxidants and stabilizers act sacrificially and are converted to oxidation products in the process of preventing polymer degradation. In most cases, little is known about the toxicity of antioxidant transformation products, and in some cases there is reason to suspect that they may be more toxic than the chemicals from which they are derived.

Two possible solutions are presently showing promise. The first is to chemically react the antioxidant or stabilizer with the polymer, either at the polymer synthesis stage or preferably during processing, so that neither the antioxidant nor its transformation products can be leached into food. The second is to use a biological antioxidant (e.g. a-tocopherol) whose oxidation chemistry and toxicology are known.

Antioxidants and stabilizers in the manufacture of packaging

Oxidation of polymers and the role of antioxidants All polymers used in the packaging industry are subject to oxidation, and the

rate at which this occurs depends on their chemical structure and the conditions to which they are exposed during manufacture and use [I]. The straight-chain paraffinic hydrocarbon polymer, polymethylene (I) (Fig. I), is relatively resistant to both thermo- and photo-oxidation when made in the laboratory by decomposi- tion of diazomethane. However, commercial polyethylene (11) is not polymethylene, since it contains appreciable amounts of pendent alkyl groups and, even more importantly, olefinic unsaturation as a result of its method of manufacture. Polypropylene (111, R = CH3) and other related poly-a-olefins are even more susceptible to oxidation due to the very high concentrations of tertiary hydrogen atoms.

23 5

236 Antioxidants in food packaging: a risk factor?

R R I

- (CH2CH) n -

Fig. I. Chemical structure of (I) polymethylene, (11) polyethylene and (111) polypropylene.

However, by far the major cause of environmental instability of the carbon- based polymers is the hydroperoxide group which is introduced during the processing operation [ 1,2]. T o convert polymers into containers or films involves both high temperatures and mechanical action on the polymer in the viscous state. Furthermore, since it is impossible to exclude oxygen during processing, the macroradicals that are produced by shearing of the polymer chains react with oxygen to produce hydroperoxides. This is shown typically for poly(viny1 chloride) (PVC) in Scheme 1 [2], but similar mechano-oxidation occurs with other polymers. Consequently, if the subsequent chain reaction is not inhibited at this stage, extensive oxidation of the polymer will occur. This results, in the case of polypropylene, to molar mass reduction, in polyethylene to cross-linking and in PVC to intense discolouration due to polyconjugation [2]. All these processes are technologically unacceptable since they result in changes in polymer rheology during processing and impairment of polymer performance in service. The hydroperoxidic species, if not destroyed during the manufacturing process, lead to subsequent environmental degradation of the final product, particularly when the artifact is to be exposed to the outdoor environment [3]. Processing stabilizers are therefore added to the polymer before it is extruded or injection-moulded in order to minimize the formation of hydroperoxides which are the primary cause of molecular mass change both during manufacture and use [2].

1 1

Scheme I. Mechanodegradation of PVC.

Antioxidant and stabilizer mechanisms Antioxidants and stabilizers fall into two main classes; those which prevent

the formation of free radicals from hydroperoxides and those which interrupt the radical chain reaction, see Scheme 2 [4-61. Typical examples of chain-breaking and preventive antioxidants are listed in Table 1. By the very nature of their interven-

G. Scott 237

RO.+-OH R- ROO.

METAL IONS W LIGHT

Scheme 2. Mechanisms of antioxidant action.

tion in the removal of free radicals or their precursors from polymers, antioxidants and stabilizers act sacrificially and are partially or wholly transformed to secondary products in exerting their protective effect. These chemical transformations can normally be followed analytically in the polymer during processing. PVC stabilizers act by the preventive mechanism, removing the redox pro-oxidant species (hydrogen chloride and hydroperoxides) produced during processing [2] (see Table I). One of the most effective 'food approved' PVC stabilizers used in packaging is dibutyl tin maleate (XVII; Table I), and the chemical tranformations occurring during processing in PVC are shown in eqn. (I) .

The end products are the potentially toxic chemicals, maleic anhydride and dibutyl tin chlorides [A. This reaction is complete within IO min when PVC is processed at 210°C [i'l.

Maleic anhydride itself, although not an antioxidant, is known to undergo a Diels-Alder reaction with polyenic unsaturation, thus effecting the removal of part of the colour [SI. However, this reaction eliminates from the polymer only a small proportion of the free maleic anhydride present (,.. 1.5 g/IOO g) as a result of eqn. (1) ['I.


Table I. Antioxidant classification.

Mechanism Codehame Examples

A. Chain breaking (CB) I. Electron donors (CB-D) ROO'+AH + ROOH+A'

IVa, BHT IVb, 1076 IVC, I010

V, IPPD 2. Electron acceptors (CB-A) R' + A' -+ RH (C=C) + AH

VI, G'

K+A' + RA

Oxidation

RA +A*

Hindered phenols OH

R R=CH3 R = CHzCHzCOOC18H37 R = (-CH2CHZCOOCH2)4C Aromatic amines

R = iso-Pr

'Stable' phenoxyls/semiquinones 3-G. VII, BQH' ;&;

OH

VIII, SQH' tBU tBU

tBU tBu

'Stable' nitroxyls

m2)4-12

IX, 770

Me Me 'Spin traps'

X, MNP tBuN=O XI, MHPBN Me

Me

G. Scott

Table I (contd.)

239

Mechanism Codehame Examples

3. Catalytic (CB-A/CB-D) A' + R' + [AR] [AR] + AH + RH(=C) AH +ROO' + A'+ ROOH

where A is > N-O', G', BQ or BQH' and AH is >N-OH, GH, BQH' or HQ

B. Preventive I . Hydroperoxide decomposers

(PD) I. I. Catalytic (PD-C)

I .2. Stoichiometric (PD-S) 2. Metal deactivators (MD)

3. Hydrogen chloride scavenger and dienophile

XII, DLTP (C12H250COCH&S XIII, ZnDC (R2NCSS)2Zn XIV, ZnDP [(R0)2PSS]2Zn

XVI tBu XV, TPP P(OPh)3

4. Hydrogen chloride scavenger XVIII, DOTG O ~ t ~ S n ( S C H ~ C 0 0 0 c t ) ~ and peroxide decomposer

5. UV absorbers

OH

Many C B antioxidant transformation products are able to redox-cycle during processing through reduction by macroalkyl radicals in the polymer. The hindered phenols (IV; Table I) are widely used as processing stabilizers (mechanoanti- oxidants) for hydrocarbon polymers. The main products formed when butylated hydroxytoluene (BHT; IVa) is oxidized are electron (hydrogen) acceptors, VI-VI11 (see Table 1). These are much more effective than BHT itself as processing stabilizers [9,10], and this has been shown to be due to the cycling of the oxidized and reduced forms of the transformation products in the reducing environment of the processing operation. This catalytic antioxidant mechanism cannot occur efficiently at ambient oxygen pressures, since it requires an appreci-


able alkyl radical concentration to reduce back the phenoxy1 radical to the parent phenol, and alkyl radicals react extremely rapidly with oxygen. Thus peroxyl formation competes with the CB-A reaction and peroxyl radicals are removed by the reduced form of the antioxidant, completing the redox antioxidant cycle. Detailed studies have shown that during high temperature processing of polymers the high shearing forces acting on the polymer in the viscoelastic state, coupled with the low concentrations of oxygen in the system, leads to the rapid regenera- tion of the CB-D antioxidant during the early stages of the reaction. The chemistry of the ‘redox antioxidant’ process has been discussed in detail elsewhere [2], but it should be noted here that, because it is a catalytic process, VI-IX (Table 1) are highly efficient processing stabilizers.

Designing ‘safe’ antioxidants for food packaging

Most low-molar-mass additives are able to diffuse relatively rapidly through polymeric substrates and in contact with fats and oils and are readily removed from the package [ 11 -131. Consequently, there are strict regulations in most countries about allowed additives in packaging [14,15]. Antioxidants and stabilizers have to undergo a rigorous toxicity testing regime before they are licenced as food contact additives. However, in commercial practice, the potentially toxic derived transformation products formed in the package during its manufacture have generally not been tested at all.

In view of the immense amount of work that would be involved in evaluating the toxicity of all the possible transformation products that might be formed from commercial ‘approved’ antioxidants, recent research has looked in different directions to find a solution to this problem. The first approach is to attach antioxidants and stabilizers to polymers through covalent bonds, so that they cannot be lost from the polymer matrix either during the processing operation or during subsequent service. The second is to use, in packaging materials, only antioxidants that are normally present in the human body or are approved foodstuffs additives whose transformation chemistry has already been studied. The former include the tocopherols and the ubiquinones and the latter the organo- soluble ascorbyl esters and the flavanoids, many of which are accepted for foodstuffs use. Some of these are also available commercially and relatively cheaply because of their increasing use as dietary supplements.

Polymer-bound antioxidants and stabilizers A great deal of work has been done in both academic and industrial labora-

tories to chemically attach antioxidants to polymers through covalent bonds [16]. Two main ways of reacting antioxidants with polymers are known: (a) co-poly- merization of vinyl monomers containing antioxidant groups during the conven- tional manufacture of polymers and (b) grafting of an antioxidant containing a polymer-reactive group to a commercial commodity polymer by reactive processing.

Both the above processes are used commercially, but the first is costly and is only used for high-value engineering products, where stability cannot be achieved

G. Scott 24 I

in any other way. Consequently, it cannot be envisaged as a commercial solution for packaging plastics, where cost is of the essence. The second procedure is much more versatile, since it does not require the production of a new speciality polymer for each application and the stabilizer-modified polymer can be 'tailor- made' during polymer conversion into the fabricated product.

Reactive processing of polymers utilizes internal mixers and extruders as chemical reactors. One of the earliest applications of the technique was to attach thiol antioxidants (ASH) to polyunsaturated rubbers by using the free macroradicals formed by shearing of the polymer chain (see section entitled Oxidation of polymers and the role of antioxidants) to initiate the Kharasch addition of thiols to double bonds in the polymer chain [17,18], see eqn. (2);

R' I

ASH + R'CH=CHR" - ASCHCH2R" (2)

where A is an antioxidant or stabilizer group. This process, although very useful in rubber-modified polymers, has limited

application in saturated polymers due to the very low concentrations of olefinic unsaturation normally present. It can, however, be used in PVC, since unsaturation is the primary product of its mechanodegradation (see Scheme 1 ) . Total attachment of thiol antioxidants (e.g. BHBM, XX)

OH

C H ~ S H

to PVC has been observed during processing [ 191. A different solution has been found for the saturated polyolefins

[ 17,18,20-221. This involves the grafting of unsaturated esters to the hydrocarbon chain by reactive processing. Two modifications of this procedure have been developed.

(a) The first utilizes a symmetrical diester of maleic acid (XXI), where A is an antioxidant or stabilizer group and PH is a polymer. Symmetrical maleate esters, unlike vinyl monomers, do not readily homopolymerize, but in the presence of a peroxide radical generator (ROOR), they form adducts, XXII, on the polymer backbone in very high yield [see eqn. (3)].

COOA COOA / /

CH ROOR P-CH

CH + PH b CH7 II I \

COOA COOA \L

XXI XXII


(b) A second method involves the grafting of vinyl antioxidants, XXIII, in the presence of a radical generator and a co-agent [21,22] [see eqn. (4)].

ROOR CH26HCOOA I

CH2=CHCOOA + PH - PCH2CHCOOA GRAFT (4)

XXIII Co-ag XXIV It has been shown that widely used commercial antioxidant structures when

covalently attached to polyolefins by the above techniques cannot subsequently be removed by the physical processes involved in the normal food contact applications of packaging materials [ 16,181.

a-Tocopherol and i ts oxidation products as processing stabilizers for polyolefins

At first sight there would seem to be an obvious benefit from using the antioxidant constituents of foodstuffs as processing stabilizers for packaging plastics. The foodstuffs additive industry has a long history [4,23] and consequently there is a wide range of non-toxic products potentially available. However, as was indicated above, the non-toxicity of the chemical initially incorporated into the polymer does not guarantee that its derived oxidation products formed during processing will also be innocuous.

We chose to study a-DL-tocopherol in some detail because it is readily available commercially and there is a good deal of information on its oxidation products [24,24a]. The major oxidation products formed from a-tocopherol are a-tocopheryl-p-quinone (a-Toc-q) , the dehydrodimer (a-Toc-dhd) and the oxidized spirodimer (a-Toc-sd) (see Scheme 3) and these are all found in animal tissues and in edible oils [25]. The dimers are excreted as such, and the p-quinone as the hydroquinone.

Initial studies had shown that a-tocopherol was a more effective processing stabilizer for polypropylene (PP) than any of the commercial synthetic antioxidants (e.g. Irganox 1010, IVc) currently in use [26]. It was not a very effective heat (air oven) or light stabilizer for PP, but as was seen above, this is not a serious disadvantage and could be a positive advantage in packaging which is used once and then disposed of. The major species identified as transformation products of a-Toc-OH when used as a processing stabilizer for PP are a-Toc-sd, a-Toc-st, a-Toc-q and aldehydes formed by methyl group oxidation are minor products (S. Issenhuth, S. Al-Malaika and G. Scott, unpublished work). a-Toc-q is an effective mechanoantioxidant due to its ability to redox cycle by the catalytic CB-A/CB-D mechanism outlined in Table 1 (2.-A. Lin, S. Al-Malaika and G. Scott, unpublished work). This is particularly interesting in the light of its close structural relationship to the ubiquinones which are known to redox-cycle synerg- istically with a-Toc-OH in vivo [27]. a-Toc-q is the major product formed under photo-oxidative conditions (T. Konig, S. Al-Malaika and G. Scott, unpublished work) and this is consistent with the poor photostability of polyolefins stabilized with a-Toc-OH.

It was seen earlier that commercial phenolic antioxidants are transformed during processing to quinonoid products and that these are generally more

G. Scott 243

U-Toc-OH

o ~ R I

I A OmR ‘0

OH

I ‘0 . HO

CH2 U-T~c-dhd I

U-TW-q

R

u-Toc-qm

H*R

1 ROO.

U-Toc-4

Scheme 3. Oxidation of a-tocopherol.

effective processing stabilizers than the phenols from which they were derived. Since all the oxidation products of a-Toc-OH are quinonoid (see Scheme 3), it seemed possible that the same reversible (redox) antioxidant mechanism might operate with the oxidation products of a-Toc-OH. It has been found (S. Issenhuth, S. Al-Malaika and G. Scott, unpublished work) that all the quinones derived from a-Toc-OH are effective processing stabilizers and that the oxidation sequence outlined in Scheme 3 is partly reversed under the strongly reducing conditions (presence of macroalkyl radicals) in a screw extruder. a-Toc-sd can also be readily reduced by mild reducing agents to a-Toc-dhd, which is itself an effective processing stabilizer. Even a-Toc-OH reduces a-Toc-sd to a-Toc-dhd in refluxing xylene [28]. However, a-Toc-dhd, like a-Toc-q, cannot be reduced back


R ' / R (R-) - b 2 - -&=CH- (RH (M))

Scheme 4. Redox (catalytic) antioxidant activity of a-tocopherol spirodimer (a-Toc-sd).

to a-Toc-OH. It appears then that a-Toc-sd and a-Toc-dhd can redox-cycle reversibly, removing both alkyl and alkylperoxyl radicals (see Scheme 4), almost certainly through the semiquinone in the same way as for other quinones/ hydroquinones.

Finally, it is known that in vivo a-Toc-0' can also redox cycle with a-Toc- OH in the presence of reducing agents. If this could be achieved in the polyolefins during processing then this would extend the period of activity of a-Toc-OH and delay the formation of inactive end-products. Initial attempts to recycle a-Toc-0' with ascorbyl esters have not proved successful due to the instability of the ascorbyl moiety under processing conditions (2. Lin, S. Al-Malaika and G. Scott, unpublished work). Other non-toxic naturally occurring reducing agents are being examined.

Conclusions

Commercial antioxidants and stabilizers undergo chemical transformations during the manufacture of packaging to give products of unknown toxicity. It seems inevitable in the light of the known physical chemistry of the migration of additives from polymers into contacting foodstuffs that these end up, at least in part, in the food chain.

Two possible strategies are discussed to prevent the contamination of foodstuffs by the oxidation products of processing stabilizers. These are: (a) covalent attachment of antioxidants to polymers during synthesis or during polymer conversion to fabricated products; (b) the use of antioxidants which are found already in the human body or which are normal constituents of foodstuffs. Experience with a-tocopherol and its oxidation products suggest that these may be candidates for the latter approach and that the mechanism of their action is related to that occurring in vivo.

G. Scott 245

I am grateful to many co-workers who have contributed to the studies reported and particularly to my colleague Sahar Al-Malaika and to Zau-an Lin, Thomas Konig, and Silvie Issenhuth for their contributions to the a-tocopherol studies not so far published. We are also grateful to F. Hoffman-La Roche for supporting these studies and to Drs. A. Liniger, F. Nabholz, M. Gmunder and D. Burdick of F. Hoffman-La Roche for helpful discussions and samples of research chemicals.

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antioxidants in food packaging: risk factor?the end products are the potentially toxic chemicals,...

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