During the first 6 months of this period work continued on the optimisation and industrial upscaling of the fermentation processes with analysis of the relation between cost and performance with the aim to define the most suitable processes and then provide a final analysis of costs. Work on the PVC Plasticisirig Process using Natural Plasticisers included:

• Iterative optimisation of the compounding process for the selected grades of plasticised PVC
• Industrial upscaling of the plasticisers manufacturing process and estimation of costs
• Production of batches of P-PVC plasticised with natural plasticisers for prototypes

Work also continued on the definition of the health safety of the natural P-PVC developed. This included:

• Definition of the threshold level of cytotoxicity of the potential natural plasticiser released
• Definition of the haemocompatibility level of the potential natural plasticiser released

Production of natural P-PVC Products in medical devices included optimisation of both film manufacture (blood bags) and extruded products (medical tubing. Work relating to the use of natural P-PVC products in toys included optimisation of injectionfor small toys and of Rotational Moulding for hollow components).

Following the unsuccessful evaluation of the batches of PCL-PC modified to have a low phenol content, the catalyst was identified as a possible source of the textural anomaly. To avoid any problems associated with the presence of heterogenous catalyst a liquid catalyst was selected instead and a 1kg scale batch of PCL-PC was prepared by this method. Investigation by microscopy revealed crystalline domains within the unblended polymer and it was thought that this crystallisation may be a source of the rough surface found in the PVC blends.To reduce the crystallinity of the material, copolymers were prepared using PEG. Having a random arrangement of PEG and PCL segments in the polymer chains was intended to suppress the crystallinity of the material. Two batches of material were prepared on a 1kg scale and evaluated further.

Further to this, the preparation of a polymer based on propanediol and succinic acid, monomers currently being developed from renewable resources, has been carried out. Copolymerisation of the two renew-type monomers gave polypropylenesuccinate-diol which was chain extended with diphenyl carbonate and polycaprolactone diol.

Investigation was also begun into sourcing materials and the identification of a suitable contractor for industrial scale synthesis of plasticisers.

Environmental Analysis of the Prototypes included comparative Life Cycle Assessment for Blood Bags and for the medical tubing.

This work resulted in a technical report on upscaling of production of plasticisers from renewable resources and economics of the process as well as in-plant demonstration of the industrial processes developed for production of plasticisers from renewable resources. In addition samples of final P-PVC produced using plasticisers from renewable resources became available.

Due to the poor performance of some materials and discolouration of others it was decided in the next six month period to focus on materials based on polytrimethylene carbonate, due to their excellent performance during evaluation. Following the successful preparation of polytrimethylene carbonate in three small scale development batches, the synthesis was scaled-up to 20L batch size, giving a target yield per batch of ca. 3kg. The first batch was successful and it was also noted that the reaction could be carried out in the absence of vacuum treatment, which greatly improves the industrial competitiveness of the process. Three further batches of this material have been produced, giving in excess of 12kg of intermediate for the development and large scale production of final plasticisers. It is evident from these batches that the process is successful in producing suitab'e material with a high degree of reproducibility.

While it was possible to estimate the costs and indicate the technical requirements of the process for each of the types undergoing evaluation, and this was in fact done, the cost of production of final material was dependent on the selection of the optimum plasticiser. The cost estimates produced are exclusive of labour and overheads but suggest further cost reductions are feasible on development of production at industrial scale.

The most suitable type of P-PCL has been selected for scale up. Development and production of this material is scheduled to begin in month 30. This will allow such as the optimisation of the P-PVC processing and development of various prototypes.

Work carried out to date involved the completion of workpackage I, in the form of a survey of publicly available literature relating to the specific areas addressed as follows:

Task 1.1 Technical Requirements for P-PVC in medical use.

• Definition of techno-economic-health constraints

Task 1.2 Technical Requirements for P-PVC in toys

• Definition of techno-economic-health constraints
• Broad Screenings of toys in P-PVC

The information obtained was subdivided into the following subject areas and presented to all partners, on CD-ROM, as a list of abstracts, bibliographies and Internet links. Abstracts covered general information, standards. Technical and processing aspects, health issues, economic issues, patents, plasticiser replacements and material replacements for toys, medical devices and other associated products.

The workpackages covering areas of experimental work in this time period were as follows:

Workpackage 2

Task 2.2 Prototype Set-Up of Fermentation Processes for Monomers

• Preliminary definition of minimal purity for further polymerisation
• Set-up of the fermenters and initial fermentation and purification process

Workpackage 3

Task 3.1 Development of Base Plasticisers and Polyester Blocks

• Analysis of technical, processing and health properties with decision on base plasticisers
• Optimisation through iteration and block size

Task 3.2 Optimisation of Base Plasticisers by Block Copolymerisation

• Development of p-pvc by using block modified plasticisers and standard conditions.
• Analysis of technical, processing and health properties with decision on suitable modiriers.
• Optimisation of the structure of the modified plasticisers with definition of final-structures.

During this period effort was focused on developing synthetic methods for plasticiser production. This was done first at a small test scale and subsequently increased to the kg scale producing sufficient for the first evaluation of the performance of these materials. This would not only enable completion of the tasks in workpackage 3, but also be directly applicable to work ongoing in the other areas noted above.

The target materials were defined and developed in cooperation with the relevant project partners, based on the technical, processing and health requirements of the materials.

At the end of the first year, the test scale work had successfully met the target specifications and the first scale-up to 1 kg for evaluation was ongoing. During the next six months the work detailed above continued with an emphasis on developing the polymerisation methods from the one kg initial scaleup to production at a rate of 5-7.5kg.

Production of the first kg of material was achieved, as planned, prior to the 12- month meeting. However, it became apparent that the materials produced to that date might not be suitable based on the results of an evaluation of a sample of the material. The problems appeared to be due to the vaporisation of phenol contained within the polymer matrix that occurred on extrusion. It was found that came not only from 'free' phenol but also latent phenol, present as phenyl ester end groups. At the extrusion temperature, further post-polymerisation chain extension can occur, producing additional phenol that becomes gaseous, forming bubbles within the extruded PVC-plasticiser blend.

In spite of this problem some further work was carried out using the one kg sample, although it was likely that the same problem would be noted, it was possible to assess the suitability of other characteristics of the polymer. In the meantime several options were considered as means of eliminating the problems found on extrusion. The procedures to solve this problem and various methods of plasticiser modification tried were as follows.

The level of phenol present in samples of Bioflex material was assessed using gel permeation chromatography with UV detection. Extrusion conditions were simulated by immersion in an oil bath held at 210 degrees C for one housr. The first kg of material was assessed in this way and gave phenol values of 0.005wt% prior to heat treatment and 0.131 wt% after heating.

In terms of reducing the free phenol it was apparent that thorough washing with ether following precipitation into ether of a chloroform solution of the polymer not only gave the best result in terms of free phenol content but was also more convenient than an alternative method using NaOH. Removal of latent phenol was also attempted by substitution of the phenyl terminus, capping the hydroxyterminus or improving the stochiometry. Substitution was not possible due to lysis of the main chain ester groups that occured in addition to removal of phenol from the chain end.

An alternative to this is to cap the hydroxyl end of the chain. This was achieved by treatment of the polymer in chloroform solution with acyl chloride/triethylamine. This gave a material with a phenol content below detection level in the precipitate and only 0.005wt% on heat treatment, a reduction by a factor of 25. However the presence of triethylammonium hydrochloride as a contaminant, which sublimes on this heat treatment, caused a similar problem to that remedied. Although removal of this contaminant is possible it would complicate the process, and so this method was set aside while method E was assessed. This involved the use of stoichiometric differences between the diol and diphenylcarbonate monomers. This reaction gave a polymer with a heat treatment phenol level of 0.013wt%.

High temperature non-stoichiometric chain extension were successful in removing noticeable bubbling from the heat-treated product. A high temperature step was included in the above method to increase the level of conversion, which should considerably lower the level of phenol generation. The inclusion of this high temperature step worked well and as anticipated gave a material with very low phenol levels both prior to and after heat treatment, with a reduction factor of 50 compared to that from the first evaluation material. This material was assumed suitable for scale-up, prior to completion of its evaluation. A 6kg scale reaction was carried out according to this method, of which a 1 kg portion has been precipitated and is ready for dispatch for completion of analytical work.