Table 4.

List of existing pharmaceutical preservatives and their problems.

Preservative & Its Structure	Category	Toxic Effect	Pharmaceuticals	References
Benzalkonium chloride solution, I.P (BAK) Ocular Preservative	Quaternary ammonium compound	Ocular toxicity, cytotoxicity, redness, dry eye syndrome, nasal mucosal damage, conjunctiva, post-operative inflammation, bacterial resistance, impairs tear film, genotoxicity, trabeculectomy failure, leaching of the eye lens, cataract, etc.	Eye/ear drops, nasal drops, multisurface disinfectants, Dettol, Savlon, Lysol, etc.	[68,122,123,124,125,126]
BHA   BHT	Phenolic compounds	Gastric irritant, endocrine disruptors, and may cause cancer	Gels, creams, liquid and gelatin capsules	[127,128,129]
R = an alkyl group Methyl paraben, ethyl paraben, propyl paraben, isobutyl paraben, butyl paraben	Paraben	Sensitization, contact dermatitis, estrogenic effect interferes with male reproductive functions, breast cancer, contact eczema, development of malignant melanoma, etc.	Local anesthetic (bupivacaine hydrochloride injection I.P.), injections (Afkim 500, gentamicin, amikacin sulphate, dexamethasone sodium phosphate injection I.P.), shaving cream, etc.	[130,131]
Quaternium-15	Formaldehyde releaser	Sensitization, allergic contact dermatitis	Eye drops, contact solutions	[131,132]
Thiomersal	Mercurial	Genotoxicity, apoptosis, cytotoxicity, neurotoxicity, neurodevelopmental and CVS disorders	Vaccines (inactivated influenza vaccine, meningococcal polysaccharide vaccine, tetanus toxoid, DTP), contact lens solutions, disinfectant (merthiolate),	[65,68,133]
Chlorobutanol	Alcohol	Not used in aerosol dispensers, cytotoxicity, retinal toxic irritation	ophthalmic ointment, ear drops, eye and nasal drops, injections, sedatives, etc.	[65,134]
Benzyl Alcohol	Alcohol	Contact dermatitis, mucous membrane irritation, CNS depression, lethargy, metabolic acidosis, toxicity of fatal development, and respiratory abnormalities, etc.	Injectable drugs (anti-inflammatory, neuroleptics), cream, and lotion, etc.	[135,136,137,138]
Phenoxyethanol	Glycol ether	Eye and skin irritation, allergic reactions such as contact urticaria and contact dermatitis, etc., are rare.	DTwP vaccines, DTaP vaccine	[139,140,141]
Stabilized Oxychloro complex (second generation ocular preservatives)	Oxidative complexes (soft preservatives)	Cytotoxicity	Eye drops	[68,125]
Sodium perborate (GenAqua)
Chlorhexidine	Amidines or biguanides	Ototoxic, nausea, stomach irritation, respiratory distress syndrome	Eye drops, antiseptic mouthwashes	[68,142]
Polyhexamethylene biguanide (PHMB)	Polyhexanide	Carcinogenic, contact allergy, conjunctival staining, corneal staining, pain after instillation, conjunctival hyperemia	Eye drops, contact lens solutions	[143]
Ascorbic acid	Organic acid	Nausea, vomiting, headache, heartburn, and cramps	Eye drops	[80,81,82]
Benzoic acid	Acids and their salts	Carcinogenic, irritation, metabolic acidosis, asthma, convulsions, etc.	Ointments, liquid preparations	[83,84,85]
Sodium benzoate	Acids and their salts	Allergy, asthma, skin rashes, hyperactivity, liver cirrhosis, Parkinson’s disease, etc.	Oral suspension, mouthwash, syrup, janam ghunti, etc.	[83,84,85,87]
Citric acid	Acids and their salts	Numbness, rapid weight gain, cramps, mood changes, severe stomach pain, diarrhea and convulsions, etc.	Powder and vitamins, etc.	[86]
Sorbic acid	Acids and their salts	Contact dermatitis, and urticaria	Emulsions	[87]