Isothiazolinones in Laundry Detergent
The extremely low prevalence of laundry detergent–associated ACD reported by the NACDG was determined prior to the start of the worldwide MI allergy epidemic, raising the possibility that laundry detergents containing isothiazolinones may be associated with ACD. There is no consensus about the minimum level at which isothiazolinones pose no risk to consumers,16-19 but the US Expert Panel for Cosmetic Ingredient Safety declared that MI is “safe for use in rinse-off cosmetic products at concentrations up to 100 ppm and safe in leave-on cosmetic products when they are formulated to be nonsensitizing.”18,19 Although ingredient lists do not always reveal when isothiazolinones are present, analyses of commercially available laundry detergents have shown MI concentrations ranging from undetectable to 65.7 ppm.20-23
Published reports suggest that MCI/MI in laundry detergent can elicit ACD in sensitized individuals. In one case, a 7-year-old girl with chronic truncal dermatitis (atopic history unspecified) was patch tested, revealing a strongly positive reaction to MCI/MI.24 Her laundry detergent was the only personal product found to contain MI. The dermatitis completely resolved after switching detergents and flared after wearing a jacket that had been washed in the implicated detergent, further supporting the relevance of the positive patch test. The investigators suspected initial sensitization to MI from wet wipes used earlier in childhood.24 In another case involving occupational exposure, a 39-year-old nonatopic factory worker was responsible for directly adding MI to laundry detergent.25 Although he wore disposable work gloves, he developed severe hand dermatitis, eczematous pretibial patches, and generalized pruritus. Patch testing revealed positive reactions to MCI/MI and MI, and he experienced improvement when reassigned to different work duties. It was hypothesized that the leg dermatitis and generalized pruritus may have been related to exposure to small concentrations of MI in work clothes washed with an MI-containing detergent.25 Notably, this patient’s level of exposure was much greater than that encountered by individuals in day-to-day life outside of specialized occupational settings.
Regarding other isothiazolinones, a toxicologic study estimated that BIT in laundry detergent would be unlikely to induce sensitization, even at the maximal acceptable concentration, as recommended by preservative manufacturers, and accounting for undiluted detergent spilling directly onto the skin.26 Nonetheless, a single European center recently reported that almost half of the 38 patients with positive patch tests to BIT had a potentially relevant exposure attributed to household cleaning products, including laundry detergent.13 This emphasizes the need for further examination of sources of exposure to this increasingly common positive patch test allergen.
Does Machine Washing Impact Allergen Concentrations?
Two recent investigations have suggested that machine washing reduces concentrations of isothiazolinones to levels that are likely below clinical relevance. In the first study, 3 fabrics—cotton, polyester, cotton-polyester—were machine washed and line dried.27 A standard detergent was used with MI added at different concentrations: less than 1 ppm, 100 ppm, and 1000 ppm. This process was either performed once or 10 times. Following laundering and line drying, MI was undetectable in all fabrics regardless of MI concentration or number of times washed (detection limit, 0.5 ppm).27 In the second study, 4 fabrics—cotton, wool, polyester, linen—were washed with standard laundry detergent in 1 of 4 ways: handwashing (positive control), standard machine washing, standard machine washing with fabric softener, and standard machine washing with a double rinse.28 After laundering and line drying, concentrations of MI, MCI, and BIT were low or undetectable regardless of fabric type or method of laundering. The highest levels detected were in handwashed garments at a maximum of 0.5 ppm of MI. The study authors postulated that chemical concentrations near these maximum residual levels may pose a risk for eliciting ACD in highly sensitized individuals. Therefore, handwashing can be considered a much higher risk activity for isothiazolinone ACD compared with machine washing.28
It is intriguing that machine washing appears to reduce isothiazolinones to low concentrations that may have limited likelihood of causing ACD. Similar findings have been reported regarding fragrances. A quantitative risk assessment performed on 24 of 26 fragrance allergens regulated by the European Union determined that the amount of fragrance deposited on the skin from laundered garments would be less than the threshold for causing sensitization.29 Although this risk assessment was unable to address the threshold of elicitation, another study conducted in Europe investigated whether fragrance residues present on fabric, such as those deposited from laundry detergent, are present at high enough concentrations to elicit ACD in previously sensitized individuals.30 When 36 individuals were patch tested with increasing concentrations of a fragrance to which they were already sensitized, only 2 (5.6%) had a weakly positive reaction and then only to the highest concentration, which was estimated to be 20-fold higher than the level of skin exposure after normal laundering. No patient reacted at lower concentrations.30
Although machine washing may decrease isothiazolinone and/or fragrance concentrations in laundry detergent to below clinically relevant levels, these findings should not necessarily be extrapolated to all chemicals in laundry detergent. Indeed, a prior study observed that after washing cotton cloths in a detergent solution for 10 minutes, detergent residue was present at concentrations ranging from 139 to 2820 ppm and required a subsequent 20 to 22 washes in water to become undetectable.31 Another study produced a mathematical model of the residual concentration of sodium dodecyl sulphate (SDS), a surfactant and known irritant, in laundered clothing.32 It was estimated that after machine washing, the residual concentration of SDS on clothes would be too low to cause irritation; however, as the clothes dry (ie, as moisture evaporates but solutes remain), the concentration of SDS on the fabric’s surface would increase to potentially irritating levels. The extensive drying that is possible with electric dryers may further enhance this solute-concentrating effect.
Differential Diagnosis of Laundry Detergent ACD
The propensity for laundry detergent to cause ACD is a question that is nowhere near settled, but the prevalence of allergy likely is far less common than is generally suspected. In our experience, many patients presenting for patch testing have already made the change to “free and clear” detergents without noticeable improvement in their dermatitis, which could possibly relate to the ongoing presence of contact allergens in these “gentle” formulations.7 However, to avoid anchoring bias, more frequent causes of dermatitis should be included in the differential diagnosis. Textile ACD presents beneath clothing with accentuation at areas of closest contact with the skin, classically involving the axillary rim but sparing the vault. The most frequently implicated allergens in textile ACD are disperse dyes and less commonly textile resins.33,34 Between 2017 and 2018, 2.3% of 4882 patients patch tested by the NACDG reacted positively to disperse dye mix.10 There is evidence to suggest that the actual prevalence of disperse dye allergy might be higher due to inadequacy of screening allergens on baseline patch test series.35 Additional diagnoses that should be distinguished from presumed detergent contact dermatitis include atopic dermatitis and cutaneous T-cell lymphoma.
Final Interpretation
Although many patients and physicians consider laundry detergent to be a major cause of ACD, there is limited high-quality evidence to support this belief. Contact allergy to laundry detergent is probably much less common than is widely supposed. Although laundry detergents can contain common allergens such as fragrances and preservatives, evidence suggests that they are likely reduced to below clinically relevant levels during routine machine washing; however, we cannot assume that we are in the “free and clear,” as uncertainty remains about the impact of these low concentrationson individuals with strong contact allergy, and large studies of patch testing to modern detergents have yet to be carried out.