Isothiazolinone Biocides: Chemistry, Biological, and Toxicity Profiles

Abstract

The importance of isothiazole and of compounds containing the isothiazole nucleus has been growing over the last few years. Isothiazolinones are used in cosmetic and as chemical additives for occupational and industrial usage due to their bacteriostatic and fungiostatic activity. Despite their effectiveness as biocides, isothiazolinones are strong sensitizers, producing skin irritations and allergies and may pose ecotoxicological hazards. Therefore, their use is restricted by EU legislation. Considering the relevance and importance of isothiazolinone biocides, the present review describes the state-of-the-art knowledge regarding their synthesis, antibacterial components, toxicity (including structure-activity-toxicity relationships) outlines, and (photo)chemical stability. Due to the increasing prevalence and impact of isothiazolinones in consumer's health, analytical methods for the identification and determination of this type of biocides were also discussed.

Keywords: analysis; biocides; biological/toxicity relationships; chemistry; isothiazoles; isothiazolinones; stability.

Figure 1

Chemical structures of isothiazole and of the most frequently used isothiazolinone biocides in consumer products.

Scheme 1

Synthesis of the biocides methylisothiazolinone (MI), methylchloroisothiazolinone (MCI), and octylisothiazolinone (OIT) as described in references [11,12,13]. (A) Synthesis of MI; (B) Synthesis of MI and OIT by the one-step chlorination-cyclization of their respective 3,3′-dithiopropionamides; (C) Alternative route for the synthesis of MI.

Scheme 2

Synthesis of the biocide MI as described in reference [15].

Scheme 3

Synthesis of the biocide dichlorocthylisothiazolinone (DCOIT) as described in reference [16].

Scheme 4

Synthesis of the biocide benzisothiazolinone (BIT) as described in references [18,19,20].

Scheme 5

Synthesis of the biocide BIT as described in (A) reference [21], (B) reference [22], and (C) reference [23].

Scheme 6

Synthesis of the biocide BIT using copper catalysts as described in (A) reference [24], (B) reference [25], and (C) reference [26].

Scheme 7

Reaction pathway for the interaction of isothiazolinones and thiols from cellular components (e.g., glutathione (GSH)) [29].

Scheme 8

Reaction pathway of MCI. (A) Interaction with thiols from cellular components (e.g., GSH) and the formation of thio-acylchloride intermediates; (B) interaction of thio-acylchloride intermediates with thiols, amines, and water [29].

Scheme 9

Major degradative pathway of MI and MCI [70].

Scheme 10

Proposed photolysis pathways of BIT under UV irradiation [75].

Scheme 11

Photodegradation pathway proposed for OIT in water [76].

Scheme 12

Photolytic degradation pathways and main phototransformation products of DCOIT (Sea-Nine 211) in aqueous environment [81].