Search for new plasticizers
The addition of plasticizers in PVC aims to supply the softness and flexibility of the compound. The plasticizer occupies about one-third of the PVC employed to assemble a medical device, like an infusion set. Manufacturers used DEHP as the principal plasticizer in the previous decades due to its relatively low cost and ability to stop the destruction of red blood corpuscles (RBC).
Based on research, however, DEHP is also harmful to people, notably infants and youngsters. Since blood and chemotherapy drugs may absorb some DEHP molecules, the possibility for patients to receive the toxic substance becomes even higher. Thus, the rummage around for alternative plasticizers has been taking place.
Parameters for evaluating alternative plasticizers
Based on the paper titled “Well Over Decades Later,…The Saga of Non-DEHP PVC and Medical Devices” written by Larry Wallace, researchers used seven parameters to evaluate several alternative plasticizers. These parameters were as follows:
- Plasticizers efficiency (how much plasticizer is required to realize the identical hardness and flexibility as traditional DEHP)
- Cost (includes both stuff cost and efficiency in the final compound)
- Compatibility with other materials (that contact the tubing)
- Chemical resistance
- Long-term aging based on volatility
- Migration resistance to polycarbonate, ABS, polystyrene, or acrylic connectors or packaging
- RBC hemolysis for blood storage
The following table summarizes the ratings of all the alternative plasticizers. The plasticizer with the least total rating is the best, and the one with the highest total is the worst.
|Plasticizer (Ranking)||DEHP||DEHT or DOTP||TOTM||ATBC(citrate)||BTHC(citrate)||DOA||DINCH|
|LONG TERM AGING||3||3||1||6||2||7||3|
Alternative plasticizers for evaluation
TOTM (trioctyl trimellitate)
TOTM is an ester produced by reacting trimellitic acid with 2-ethyl hexanol. Manufacturers could consider it the plasticizer of choice for drug infusion or chemotherapy materials because of its significant chemical resistance.
It has extremely low volatility. It offers several advantages, such as good extraction resistance, suitable plasticizer and resin compatibility, permanence, and excellent performance at high and low temperatures. It provides good electrical resistance properties, resistance to chemical agents, and extraction by soapy water. In addition, it is highly resistant to external influences such as sunlight and therefore does not change color so easily. It has a high boiling point, easy to process, and has a long shelf life. It provides the desired changes to physical and mechanical properties without causing changes to the chemical structure of the polymer.
Based on Table 1, TOTM got the highest rank of 1 in compatibility, chemical resistance, long-term aging, and migration. Its principal drawbacks are efficiency factor, relative cost, and RBC hemolysis.
DINCH (di-isononyl cyclohexane)
Designers use materials with PVC to store blood. Based on Table 1, DINCH works best as an alternative to DEHP to avoid hemolysis of RBC. Hence, manufacturers could strongly consider DINCH as a possible replacement for DEHP.
However, despite some recent licensing arrangements and expansion, the problem of supply limitations remains. Furthermore, based on the study by Noha Saad et al. titled “Di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) alters transcriptional profiles, lipid metabolism and behavior in zebrafish larvae” and published in September 2021, the genes involved in cholesterol formation and internal stability were adversely affected by DINCH. The genetic alteration could also cause possible developmental damage to nerves. In addition, behavioral analysis of larvae demonstrated a distinct locomotor activity upon exposure to DINCH. The present data showed that DINCH could induce physiological and metabolic toxicity to aquatic organisms. Hence, researchers need to conduct further analyses and environmental monitoring of DINCH to determine its safety and toxicity levels.
Based on Table 1, DINCH got a rating of 2 for not causing hemolysis of RBC. Thus, using it as part of the materials for storing blood is in high order. However, it received poor ratings for the other parameters of evaluation. In addition, based on the study by Noha Saad et al., as cited in the preceding, it can cause safety and toxicity problems. Supply limitations and efficiency factors could also present additional impediments to using DINCH.
DOTP (di-octyl terephthalate) or DEHT
Designers could consider DOTP because of its low costs, excellent toxicological profile, and no adverse effects on human health. However, it failed in efficiency factors, migration, and RBC hemolysis.
ATBC (acetyl tributyl citrate) and BTHC
ATBC and BTHC are bio-based plasticizers. In terms of sustainability, they are the best plasticizers on the list. They do not pose hazards to the environment because they are both biodegradable. Both plasticizers show excellent toxicological and eco-toxicological properties. Manufacturers frequently used ATBC as the common plasticizer for gastrointestinal uses. It offers outstanding performance, non-toxic environmental protection, and a good speed-increasing effect. On the other hand, medical workers often use the BTHC for medical devices for storing blood. BTHC, however, is a very expensive plasticizer.
Based on Table 1, ATBC has the second to the worst ratings across all the parameters. BTHC also received poor ratings, although relatively better than ATBC. Poor efficiency factors and high cost pulled down the overall rating of BTHC.
DOA or dioctyl adipate demonstrates the best efficiency among the common plasticizers. It works well in low-temperature settings.1 It does not dissolve in water. In addition, it is one of the best solvents for organic matter. If this substance comes into contact with water, it will have excellent resistance. It does not melt when it reaches a temperature of 200 degrees Celsius. The other unique features are the following:
- Resistance to temperature and pressure changes
- Flexibility at low temperatures and pressures
- Nice electrical properties
- Compatibility with rubber materials
- No need to manipulate
- Heat resistance
- It can be used with other compatible plastic instruments
DOA has the worst total rating. It received a rating of 1 for the efficiency factor, but ratings in the other parameters were poor. This plasticizer is not recommendable.
Highly Recommended Plasticizer
Based on Table 1, the TOTM is the best alternative plasticizer. But since it received a low rating specifically in RBC hemolysis, DINCH could be considered for medical devices intended to hold blood for infusion or storage. The TOTM possesses the required attributes, and manufacturers can use it for other purposes.