Effects of slime toy poisoning in children and teenagers

Abstract Objective: The aim of this study was to identify which types of skin reactions are associated with slime toys and which of their ingredients are most frequently involved in cases of poisoning. Data source: Between January and July 2021, articles were selected using PubMed, SciELO, and LILACS databases. The following descriptors were used: (dermatitis OR rash OR eczema OR inflammation) AND slime. Inclusion criteria were articles available in full, in either Portuguese, English, or Spanish, published between January 2000 and July 31, 2021, and articles reporting cases of contact dermatitis or eczema potentially or directly attributed to slime toys. Articles not meeting these criteria and duplicate texts in the databases were excluded. Data synthesis: In total, 65 publications were identified, of which 16 were included in this review. This resulted in a total of 22 children (2 males, 20 females), aged between 4 and 13 years, who were reportedly intoxicated by slime toys, most of these being linked to homemade preparations. Studies reported the occurrence of contact or allergic dermatitis on hands, fingers, nails, forearms, and cheeks. The most allergenic and/or irritant ingredients included liquid detergent and soap. Additionally, patch tests identified positive reactions to methylisothiazolinone and methylchloroisothiazolinone, the preservatives used by chemical industries on preparation of glue, soap, detergents, etc. Conclusions: Although slime toys might be important for improving motor development and parental relationships, homemade slime toy recipes include several allergenic and irritant ingredients which might be exposed to vulnerable children and cause intoxications. Therefore, homemade slime toys preparations should be used cautiously and under the supervision of adults.


INTRODUCTION
Since antiquity, children's toys have been used for recreational and educational purposes. 1It is well accepted that playing is not a frivolous task and is essential for the development of children and young individuals.Indeed, playing contributes to cognitive, emotional, physical, and social welfare, as well as promotes engagement between parents and children. 2 Among children's games, manual activities, such as manipulating toys and objects, require a high level of coordination and motor skills.Recently, however, recreational activities have become more "virtual," taking place through the screen of computers and smartphones, a process that has been intensified during the new coronavirus pandemic. 3,4Indeed, the time spent by children on screens has increased while the time spent on traditional activities has reduced over the past decades, which might negatively affect the development of gross and fine motor skills. 5,6n parallel, digital media have boosted the dissemination of games and homemade toys, such as the case of the game "the floor is lava" and "the slime" toy, two famous contents in 2017 among children and teenagers.Slime is a viscous-elastic toy that became very popular among children and teenagers between 2017 and 2019. 7,8The Internet boosted the popularization of slime, making readily available several homemade recipes with ingredients easily found at home but not exempt of toxicity.Nowadays, homemade recipes for slime preparation might contain various toxic, irritating, or allergenic compounds such as borax, boric acid, glues, creams, and various dyes. 9n general, reactions to such compounds are local rather than systemic and these chemical compounds interact with the body through direct contact with hands, mouth, eyes, and nose. 10espite the potential toxic effects of homemade slime, playing with it can be beneficial for child development.For instance, playing with slime can improve children's concentration and assist on the development of fine motor coordination due to its handling actions, such as pulling, pinching, or squeezing the toy.Additionally, by preparing it, children can understand basic concepts of quantity, relation of cause and effect, and chemical reactions.Finally, it can potentially strengthen parental bounds, since it might be an activity in which children can have fun and learn together with their parents. 11,12he popularization of slime and the broad access to recipes for its homemade preparation favored the increase of cases of contact dermatitis which might be associated with slime.Considering such reports of potential toxicity related to slime and the benefits of slime handling for the development of children, we performed a systematized review to identify which types of skin reactions are caused by slime and which of its ingredients are most frequently involved in case reports of poisoning in children.

METHOD
From January 2000 to July 31, 2021, a total of 65 articles were identified from the initial search and were reviewed according to the following criteria: reporting of a case of contact dermatitis or eczema and contact dermatitis or eczema potentially or directly attributed to a slime toy.The narrative review was based on a systematic search on current literature published in the scientific databases SciELO -Brazil (Scientific Electronic Library Online), PubMed (US National Library of Medicine), and LILACS (Latin American and Caribbean Literature in Health Sciences).The criteria used for searching skin reactions associated with slime were as follows: (dermatitis OR rash OR eczema OR inflammation) AND slime, and the applied filters such that it included all English, Spanish, and Portuguese language articles published on patients aged 0-18 years.Articles not fitting the theme and duplicate texts found in the databases were excluded.
Two researchers independently searched for articles by accessing, at first, the title and abstract.Articles that did not fit the eligibility criteria and duplicate articles were excluded.Any disagreement between the two authors was resolved by a third reviewer.The full text of the remaining articles was accessed to assess inclusion in the work.Review articles were screened for other primary sources, but otherwise not included.For included articles, we collected data on study design, children age (ranging from 0 to 18 years), sex, slime toy ingredients (either from homemade or industrialized slime), site and type of reaction, suspected allergen, and whether the patient underwent allergy testing.

RESULTS
A total of 65 studies were found on the initial search; among these, 60 were found in PubMed, 3 in LILACS, and 2 in SciELO databases (Figure 1).
4][15][16][17][18][19][20][21][22][23][24][25][26][27][28] Among them, seven are from the United States, whereas the remaining are from France, Belgium, Brazil, Switzerland, Turkey, Canada, Spain, and Tunisia, published during the period between 2000 and 2021.From the selected 16 studies, 5 reported more than one case of intoxication while the remaining studies reported only a single case.A total of 20 females and 2 males, aged between 4 and 13 years, presented some type of skin reaction.It was possible to observe a higher prevalence of children with allergic contact dermatitis (ACD) or irritant contact dermatitis (ICD), affecting mainly hands, fingers, nails, forearms, and cheeks.
The reports of intoxication involved mainly the manipulation of homemade slime preparations, their ingredients being water, boric acid, glue, polyvinyl acetate glue, shaving creams, borax, sodium hypochlorite (bleach), dyes, sodium bicarbonate, detergents, washing soap, shampoo, and glitters.Some of the ingredients used for homemade slime preparation are often associated with cases of allergy and skin irritation, in particular, detergents, polyvinyl acetate glue, and liquid soap.In contrast, in most cases where reactions were due to contact with commercial slime, it was not possible to identify its ingredients.The only study able to identify the general ingredients used in a commercial slime preparation reported polyvinyl alcohol, glycerin, borax, ethyl paraben, deionized water, and various dyes on its composition.
Unfortunately, most of the studies did not inform the occurrence of previous episodes of atopic dermatitis.The studies that reported patch tests being carried out identified positive reactions for methylisothiazolinone (MI), methylchloroisothiazolinone/methylisothiazolinone (MCI/MI), methyldibromoglutaronitrile (MDBGN), and paraben mix (methyl paraben and ethyl paraben).Records excluded after analysis of title and abstract (n=40) Full-text articles assessed for eligibility (n=20) Full-text articles excluded, with reasons Didn't meet the inclusion criteria, (n=2) Retrospective case series, (n=1) Review article, (n=1) Studies included in qualitative synthesis (n=16)

DISCUSSION
According to the analysis of studies found in the current literature, it was possible to identify several reports of skin reactions induced by slime toys, especially those classified as ACD or ICD.The clinical diagnosis of ACD and ICD is difficult as these conditions cause lesions that often mimic other skin diseases that are common in children. 29ACD is an inflammatory skin disease caused by a type IV hypersensitivity reaction, the immune response occurring in previously sensitized individuals with a latency period of 48-96 h. 30On the contrary, ICD is a skin reaction caused by contact with corrosive substances and usually leads to symptoms within a period of 48 h after exposure. 30,31ven that the risks associated with the development of skin reactions and immune responses are very unique between individuals, 32 the severity and clinical evolution of intoxications caused by slime varied from severe cases of difficult management to milder cases 13,14,18,20,23 of good resolution. 15,26,27t is noteworthy that individuals who have suffered from previous episodes of atopy are more likely to develop atopic dermatitis and present more severe or intense ACD or ICD symptoms. 32,33Despite this, most studies did not inform the existence of previous episodes of atopy.Furthermore, it is well known that mildly corrosive substances can potentially damage the skin of children, as it is more fragile and sensitive in comparison to the skin of adults.Also, the severity of  the reactions can be directly proportional to the preexisting skin conditions, concentration of irritating compound, and time of exposure. 34his research highlighted that several potentially toxic, allergenic, or irritating products were used as ingredients for the preparation of homemade slime, including borate acid, polyvinyl acetate glue, sodium bicarbonate, borax, bleach, soap, and shampoo, among others.Previous study carried out by Marrero-Alemán et al. 35 reported the presence of high concentrations of allergenic or irritating compounds, such as isothiazolinones, in cleaning products.From a total of 34 products collected, 35.5% of the products analyzed for MI research had concentrations above tolerated limits by the European Commission (>15 ppm or 0.0015%). 35In contrast, in Brazil, the maximum concentration allowed for MI is 100 ppm (0.01%), while for mixtures of MI and MCI (Kathon CG) substances the maximum authorized concentration is 15 ppm (0.0015%). 36he patch test is the gold standard diagnostic method for identifying susceptibility to contact dermatitis. 28Interestingly, most studies have reported that individuals affected by slime presented a positive response for MCI and MI, which are preservatives widely used for the preparation of cosmetic and cleaning products.Previous studies have shown that the prevalence of contact allergy in response to MCI and MI is around 1.5% in the general population. 37However, Mortazavi et al. have demonstrated exacerbated response for allergens in female children and teenagers; 39 (76.47%) cases involving females vs. 12 (23.52%)cases involving males. 38In addition, Rodrigues et al. have demonstrated the incidence of positive response to patch test when the challenge is carried out with substances such as nickel, cobalt, fragrances, paraben, and thimerosal is higher in females. 39Zafrir et al. performed a series of patch tests on children suspected of having ACD and found that females showed significantly more positive reactions (n=197; 78.2% of positive results) than males (n=147; 21.8% of positive results).In this same study, the authors were also able to observe a greater presence of positive results for MI/MCI in females (n=13; 10 females vs. 3 males). 40 possible hypothesis for explaining the findings described above was raised by the study conducted by Corrêa-Fissmer et al., which suggested that females are more susceptible for developing contact dermatitis because they consume more cosmetics and hygiene products.In addition, the authors claim that females have higher exposure to allergenic substances and, in general, they are more tempted to seek medical care than males. 41he limitations of this narrative review are mainly related to the reduced number of studies on the current literature reporting cases of skin reactions associated with slime in children and adolescents.Indeed, the present review was based on data collected from few case reports published in scientific database; perhaps, a higher incidence might be present.However, it has not been reported in the literature due to the sub-notification of cases.Besides, all studies found on literature are case reports, which contain a significant variability in the description of cases.Additionally, many of such studies lack relevant data that would be important for further conclusions.For instance, the presence of atopy was not reported in 50% of the cases (11 children), while the performance of dermatological tests was not reported in 31.8% of the cases (7 children).
Taken altogether, such limitations did not allow us to compile those studies and describe our findings as a systematic review.Despite the limitations mentioned above, we foresee that our narrative review is important to highlight the potential intoxication triggered by slime for encouraging further clinical studies to investigate this problem more deeply.

CONCLUSION
The present narrative review of the current literature between 2000 and 2021 has highlighted that homemade slime might trigger skin reactions, mostly classified as ACD and ICD.Furthermore, the studies have shown that most of reported skin reactions involved female children and teenagers.The ingredients often used for homemade slime preparation (e.g., detergents, polyvinyl acetate) contain MCI and MI, which are frequently associated with positive response in patch tests in individuals affected by slime.In conclusion, homemade slime toy recipes include several allergenic and irritant ingredients which might be exposed to vulnerable children, leading to intoxications.Therefore, homemade slime toys preparations should be used cautiously and under the supervision of adults.

Figure 1 .
Figure 1.PRISMA flow diagram to selected studies

Table 1 .
Summary of articles included in this review: age and sex of the patients, presence of atopy, site, and type of reaction M: male; F: female; N/I: not informed; ACD: allergic contact dermatitis; ICD: irritant contact dermatitis.

Table 2 .
Summary of articles included in this review: slime ingredients and type, potential allergens, and dermatologic tests MCI/MI: methylchloroisothiazolinone/methylisothiazolinone; MDBGN: methyldibromoglutaronitrile; N/I: not informed.