Fragmentation Pattern-Based Screening Strategy Combining Diagnostic Ion and Neutral Loss Uncovered Novel para-Phenylenediamine Quinone Contaminants in the Environment.

Identifying transformed emerging contaminants in complex environmental compartments is a challenging but meaningful task. Substituted para-phenylenediamine quinones (PPD-quinones) are emerging contaminants originating from rubber antioxidants and have been proven to be toxic to the aquatic species, especially salmonids. The emergence of multiple PPD-quinones in various environmental matrices and evidence of their specific hazards underscore the need to understand their environmental occurrences. Here, we introduce a fragmentation pattern-based nontargeted screening strategy combining full MS/All ion fragmentation/neutral loss-ddMS2 scans to identify potential unknown PPD-quinones in different environmental matrices. Using diagnostic fragments of m/z 170.0600, 139.0502, and characteristic neutral losses of 199.0633, 138.0429 Da, six known and three novel PPD-quinones were recognized in air particulates, surface soil, and tire tissue. Their specific structures were confirmed, and their environmental concentration and composition profiles were clarified with self-synthesized standards. N-(1-methylheptyl)-N'-phenyl-1,4-benzenediamine quinone (8PPD-Q) and N,N'-di(1,3-dimethylbutyl)-p-phenylenediamine quinone (66PD-Q) were identified and quantified for the first time, with their median concentrations found to be 0.02-0.21 µg·g-1 in tire tissue, 0.40-2.76 pg·m-3 in air particles, and 0.23-1.02 ng·g-1 in surface soil. This work provides new evidence for the presence of unknown PPD-quinones in the environment, showcasing a potential strategy for screening emerging transformed contaminants in the environment.

Dermal exposure and hair dye: Assessing potential bladder cancer risk from permanent hair dye.

Hair dye products include a range of chemicals, depending on the type and color. A common primary intermediate compound used to achieve the permanent effect of hair dye is para-phenylenediamine (PPD). 4-aminobiphenyl (4-ABP) has reportedly been found as a trace contaminant (presumably from the para-phenylenediamine [PPD] ingredient) in consumer permanent hair dye. While several regulatory agencies have designated 4-ABP as a human bladder carcinogen based on evidence in humans and experimental animals, only the Office of Environmental Health Hazard Assessment (OEHHA) have established a cancer risk value for 4-ABP of 0.03 µg/day based on liver tumors developed in mice. A hypothetical dermal risk assessment was performed to estimate the bladder cancer risk associated with exposure to 4-ABP from personal use of permanent hair dye potentially containing incidental 4-ABP. Previously published laboratory analyses characterizing 4-ABP concentrations in consumer hair dyes indicate the concentrations can range from below the limit of detection to 8120 ppb. Precautionary estimates of human scalp surface area, maximum skin adherence, hair dye retention factor, and percent dermal absorption were used to estimate the daily systemic exposure doses (SEDs) from dermal application of hair dye. The estimated SEDs ranged from 0.05 to 3000 pg/day. A margin of safety (MOS) was calculated as the ratio of the NSRL to the SED and ranged from 10 to 570,000. The results of this study suggest that there is no indication of increased risk of bladder cancer in humans from exposure to 4-ABP in consumer hair dye, especially as it is extremely unlikely that a consumer would use permanent hair dye on a daily basis (as this assessment models).

Toxicity of para-phenylenediamine (PPD;1, 4 diaminobenzene) on isolated human lymphocytes: The key role of intracellular calcium enhancement in PPD-induced apoptosis.

Para-phenylenediamine (PPD) is a derivative of benzene used as an ingredient in dyes, a photographic developing agent, and a component of engineered polymers. The carcinogenicity of PPD, which has been documented in several studies, may be related to its toxic effects on different compartments of the immune system. The main goal of this research was to evaluate the mechanism of the toxicity of PPD on human lymphocytes by exploiting the accelerated cytotoxicity mechanism screening (ACMS) technique. Lymphocytes were isolated from the blood of healthy persons using a Ficoll-Paque PLUS standard method. Assessment of cell viability was carried out 12 h following treatment of human lymphocytes with 0.25-1 mM PPD. For determination of cellular parameters, isolated human lymphocytes were incubated with 1/2 the IC50 (0.4 mM), the IC50 (0.8 mM), and twice the IC50 (1.6 mM) for 2, 4, and 6 h. Half maximal inhibitory concentration (IC50) is the concentration that reduces cell viability approximately 50% following treatment. The results of this study demonstrated that PPD-associated apoptosis in human lymphocytes was mainly through the enhancement of intracellular calcium, oxidative stress, and following adverse effect on lymphocyte organelles (like mitochondria and lysosomes). Lipid peroxidation, activation of caspase-3, and stimulation of cytokines (IL2, interferon-gamma (IFN-γ), and TNF-alpha) production were also observed in PPD-treated lymphocytes. Considering the results of this study, we can suggest an association between PPD carcinogenicity and its toxic effects on different compartments of the immune system.

Beyond Substituted p-Phenylenediamine Antioxidants: Prevalence of Their Quinone Derivatives in PM2.5.

Substituted para-phenylenediamine (PPD) antioxidants have been extensively used to retard oxidative degradation of tire rubber and were found to pervade multiple environmental compartments. However, there is a paucity of research on the environmental occurrences of their transformation products. In this study, we revealed the co-occurrence of six PPD-derived quinones (PPD-Qs) along with eight PPDs in fine particulate matter (PM2.5) from two Chinese megacities, in which N,N'-bis(1,4-dimethylpentyl)-p-phenylenediamine quinone (77PD-Q) was identified and quantified for the first time. Prevalent occurrences of these emerging PPD-Qs were found in Taiyuan (5.59-8480 pg/m3) and Guangzhou (3.61-4490 pg/m3). Significantly higher levels of PPDs/PPD-Qs were observed at a roadside site, implying the possible contribution of vehicle emissions. Correlation analysis implied potential consistencies in the fate of these PPD-Qs and suggested that most of them were originated from the transformation of their parent PPDs. For different subpopulation groups under different exposure scenarios, the estimated daily intakes of PPD-Qs (0.16-1.25 ng kgbw-1 day-1) were comparable to those of their parent PPDs (0.19-1.41 ng kgbw-1 day-1), suggesting an important but overlooked exposure caused by novel PPD-Qs. Given the prolonged exposure of these antioxidants and their quinone derivatives to traffic-relevant occupations, further investigations on their toxicological and epidemiological effects are necessary.

Investigations on detoxification mechanisms of novel para-phenylenediamine analogues through N-acetyltransferase 1 (NAT-1).

Para-phenylenediamine (PPD) is one of the most used chemicals in oxidative hair dyes. However, its use has been associated with adverse effects on health, including contact dermatitis and other systemic toxicities. Novel PPD derivatives have been proposed as a safer replacement for PPD. This can be achieved if these molecules minimally permeate the skin and/or are easily metabolised by enzymes in the skin (e.g., N-acetyltransferase-1 (NAT-1)) into innocuous compounds before gaining systemic entry. This study investigated the detoxification pathway mediated by NAT-1 enzymes on 6 synthesized PPD analogues (namely, P1-P6) with different chemical properties, to study the role of functional groups on detoxification mechanisms in HaCaT skin cells. These compounds were carefully designed with different chemical properties (whereby the ortho position of PPD was substituted by nucleophile and electrophile groups to promote N-acetylation reactions, metabolism and clearance). Compounds P2-P4 N-acetylated at 54-49 nmol/mg/min, which is 1.6 times higher than N-acetylation of PPD, upregulated NAT-1 activity from 8-7% at 50 µM to 22-11% at 100 µM and showed 4 times higher rate of elimination (k equal to 0.141 ± 0.016-0.124 ± 0.01 h-1) and 3 times faster rate of clearance (0.172 ± 0.007-0.158 ± 0.005 h-1mgprotein-1) than PPD (0.0316 ± 0.0019 h-1, 0.0576 ± 0.003 h-1mg protein-1, respectively). The data suggest that nucleophile substituted compounds detoxify at a faster rate than PPD. Our metabolic and detoxification mechanistic studies revealed significantly higher rates of N-acetylation, NAT-1 activity and higher detoxification of P2-P4 in keratinocytes, suggesting the importance of nucleophilic groups at the ortho position in PPD to reduce toxicity of aniline-based dyes on human skin cells.

Para-phenylenediamine deteriorates oocyte quality by impairing mitochondrial function.

Several studies demonstrate that para-phenylenediamine (PPD) is often added to permanent oxidative hair dyes. Sub-chronic topical exposure to PPD in male rats damages their testicular function; however, little is known about the effects of PPD exposure on the female reproductive system, especially on oocyte quality. In this study, we found that PPD can affect the meiotic capacity of oocytes and their fertilization potential. In particular, PPD can damage the spindle/chromosome structure and prevent oocytes from developing and maturing normally. Furthermore, PPD exposure compromised the dynamics of cortical granules and their component, ovastacin. In addition to the protein level of Juno, the sperm receptors on the egg membrane, were substantially impaired in PPD-administered oocytes, thus leading to fertilization failure. Finally, we found that PPD exposure resulted in abnormal mitochondrial function, which led to oocyte degeneration, apoptosis, and increased ROS levels. Altogether, our study illustrates that mitochondrial dysfunction and redox perturbation are the major causes of the poor quality of oocytes exposed to PPD.

Multiple Stimuli-Responsive Supramolecular Hydrogels Constructed by Decamethylcucurbit[5]uril-para-phenylenediamine Exclusion Complex.

The hydrogels composed of decamethylcucurbit[5]uril (Me10 Q[5]) and para-phenylenediamine (p-PDA) are first reported herein. They are the first Q[5]-based supramolecular hydrogels, the formation of which is driven by portal exclusion between Me10 Q[5] and p-PDA. The composition, structure, and properties of the Me10 Q[5]/p-PDA-based hydrogels are investigated by various techniques. Since the 1D supramolecular chain forms via portal exclusion between Me10 Q[5] and p-PDA is the key to the formation of the hydrogels, any competitive species, such as metal ions, organic molecules, and amino acids, which can affect the portal exclusion, can change the behavior of the Me10 Q[5]/p-PDA-based hydrogels. Hence, the hydrogels can be used for various applications. Importantly, the results may provide a new research direction for the preparation of Q[n]-based hydrogels via portal exclusion of Q[n]s with guests.

Occupational mimics of rheumatoid arthritis: hair dye-induced arthritis.

Hair dye (HD) and its component para-phenylenediamine (PPD) are commonly used to enhance beauty and youth. HD is associated with allergic contact reactions and the development of autoimmune phenomena. A 28-year-old woman presented to us complaining of pain and swelling affecting the small joints of the hands bilaterally lasting for 7 weeks. Laboratory evaluation was remarkable only for an increase of acute-phase reactants, while the rest of laboratory tests including serological tests for viruses, as well as immunological tests were negative or within normal limits. She noticed a close correlation between the onset of symmetrical polyarthritis and the use of HD product. Thus, after excluding other possibilities of inflammatory arthritides, the diagnosis of HD-induced arthritis was made. The patient was treated with naproxen, and after 3 weeks, she had a complete clinical response with decrease of acute-phase reactants. Thus, we review and discuss the relevant literature of cases related with the use of HD and arthritis development. This is the first described case of HD-induced arthritis. Physicians must be aware and recognize these symptoms and signs of patients exposed to HD and treat them appropriately.

Hair dye and risk of skin sensitization induction: a product survey and quantitative risk assessment for para-phenylenediamine (PPD).

BACKGROUND: Para-Phenylenediamine (PPD) is a commonly used dye intermediate in permanent hair dye formulations, and exposure to PPD has been associated with allergic contact dermatitis at certain doses. PURPOSE: Determine the concentration of PPD in a survey of self-application permanent hair dye products, and perform a quantitative risk assessment to determine the risk of skin sensitization induction following application of these products. METHODS: Consumer exposure levels (CELs) to PPD following application of hair dye products were estimated using the maximum amount of hair dye that can adhere to the surface area of the scalp, the measured concentration of PPD in the hair dye product, a retention factor, the dermal absorption of PPD, and the surface area of the scalp. CELs were calculated for various exposure scenarios, and were stratified by hair dye shade. RESULTS: All estimated CELs did not exceed the acceptable exposure level. Specifically, margins of safety ranged from 2.3 to 1534 for black dyes, 2.9 to 5031 for brown dyes, and 26 to 5031 for blonde dyes. CONCLUSIONS: Findings suggest that use of the evaluated permanent hair dyes, under the evaluated exposure scenarios, would not be expected to induce skin sensitization due to PPD exposure at concentrations ≤0.67%.

The effects of para-phenylenediamine (PPD) on the skin fibroblast cells.

1. Para-phenylenediamine (PPD) is the commonest and most well-known component of hair dyes. PPD is found in more than 1000 hair dye formulations and is the most frequently used permanent hair dye component in Europe, North America and East Asia. PPD containing hair dyes have been associated with cancer and mutagenicity. Apart from that, PPD has potential toxicity which includes acute toxicity such as allergic contact dermatitis and subacute toxicity. 2. In this study, we examined the effects of the PPD composition on the skin-isolated fibroblast cells. Fibroblast cells were isolated from the skin and cell viability, reactive oxygen species (ROS) production, the collapse of mitochondrial membrane potential (MMP), lipid peroxidation (LPO), damage to the lysosome release of lactate dehydrogenase (LDH) and finally release of cytochrome c were examined following the exposure to various concentrations of PPD. 3. Our results showed that exposure to PPD increased ROS generation, LPO, the collapse of MMP, LDH release and cytochrome c release. Our results suggest that PPD can induce damage to the lysosomal membrane. 4. These results showed that PPD composition has a selective toxicity on skin fibroblasts cell and mitochondria are considered one of the goals of its toxicity.

Fluorescence Investigations on Interactions between 7,8-benzo-4-azidomethyl Coumarin and Ortho- and Para-phenylenediamines in Binary Solvent Mixtures of THF and Water.

Fluorescence investigations on interactions between 7,8-benzo-4-azidomethyl coumarin (7BAMC) and quenchers ortho-phenylenediamine (OPD) and para-phenylenediamines (PPD) in binary solvent mixtures (THF + water) have been reported. UV-absorption study indicated a weak hydrophobic interaction between 7BAMC and the para isomer. NMR spectral studies indicated the presence of an interaction between 7BAMC and PPD. Magnitudes of the parameters associated with FRET, showed the presence of interactions between 7BAMC and PPD quencher is more predominant than OPD. Fluorescence quenching studies reveal the role of static and dynamic quenching pathways, depending upon Stern-Volmer constant, dielectric constant and dominant non-radiative processes. Binding equilibria analysis indicates a strong interaction between 7BAMC and PPD than OPD and formation of H-bonding. Based on the magnitudes of free energy, enthalpy change and entropy, bimolecular interaction process may be considered as spontaneous and hydrophobic.

Hypersensitivity reactions due to black henna tattoos and their components: are the clinical pictures related to the immune pathomechanism?

Hypersensitivity to para-phenylenediamine (PPD) and related compounds induced by temporary black henna tattoos has become a serious health problem worldwide. Different patterns of sensitization with various clinical aspects are described in literature due to PPD associated to henna tattoo and these manifestations are likely correlated with the immunological and dermatological pathomechanisms involved. Henna is the Persian name of the plant Lawsonia inermis, Fam. Lythraceae. It is a woody shrub that grow in regions of North Africa, South Asia, India and Sri Lanka. Nowadays it is rather frequent to see temporary "tattoos" performed with henna. To make tattoos darker and long-lasting PPD has been associated to henna in tattoo drawings mixtures, so obtaining "black henna". In these years there has been a rise of contact sensitization to PPD and in medical literature an increased number of cases have been reported on temporary henna tattoo application. Here we review the various clinical patterns related to PPD and henna tattoo, to investigate the possible link between clinic-morphological pictures and the immunological response to PPD and henna. The literature underlines that different clinical manifestations are related to black henna containing PPD, and its derivative products may cause delayed-type as well as immediate-type reactions. Further studies are needed to investigate the relationship between clinical and morphological aspects of PPD contact dermatitis and the T cell subsets predominance.

para-Phenylenediamine induces apoptosis through activation of reactive oxygen species-mediated mitochondrial pathway, and inhibition of the NF-κB, mTOR, and Wnt pathways in human urothelial cells.

para-Phenylenediamine (PPD) has long been used in two-thirds of permanent oxidative hair dye formulations. Epidemiological studies and in vivo studies have shown that hair dye is a suspected carcinogen of bladder cancer. However, the toxicity effects of PPD to human bladder remains elusive. In this study, the effects of PPD and its involvement in the apoptosis pathways in human urothelial cells (UROtsa) was investigated. It was demonstrated that PPD decreased cell viability and increased the number of sub-G1 hypodiploid cells in UROtsa cells. Cell death due to apoptosis was detected using Annexin V binding assay. Further analysis showed PPD generated reactive oxygen species (ROS), induced mitochondrial dysfunction through the loss of mitochondrial membrane potential and increased caspase-3 level in UROtsa cells. Western blot analysis of PPD-treated UROtsa cells showed down-regulation of phosphorylated proteins from NF-κB, mTOR, and Wnt pathways. In conclusion, PPD induced apoptosis via activation of ROS-mediated mitochondrial pathway, and possibly through inhibition of NF-κB, mTOR, and Wnt pathways. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 265-277, 2017.

Allergic contact dermatitis to substitute hair dyes in a patient allergic to para-phenylenediamine: Pure henna, black tea and indigo powder.

We report a case of a 50-year-old lady with allergic contact dermatitis to para-phenylenediamine, who in her quest to find a substitute hair dye, subsequently reacted to a number of plant-based hair dyes, including pure henna, black tea and indigo powder respectively. While these substances all contain tannins, testing to possible constituents tannic acid and gallic acid was negative.

Allergic contact dermatitis to para-phenylenediamine.

Exposure to hair dye is the most frequent route of sensitisation to para-phenylenediamine (PPD), a common contact allergen. International studies have examined the profile of PPD, but Australian-sourced information is lacking. Patients are often dissatisfied with advice to stop dyeing their hair. This study examines patients' characteristics, patch test results and outcomes of PPD allergy from a single Australian centre, through a retrospective analysis of patch test data from 2006 to 2013 at the Liverpool Hospital Dermatology Department. It reviews the science of hair dye allergy, examines alternative hair dyes and investigates strategies for hair dyeing. Of 584 patients, 11 were allergic to PPD. Our PPD allergy prevalence rate of 2% is at the lower end of international reported rates. About half these patients also react to para-toluenediamine (PTD). Affected patients experience a significant lifestyle disturbance. In all, 78% tried alternative hair dyes after the patch test diagnosis and more than half continued to dye their hair. Alternative non-PPD hair dyes are available but the marketplace can be confusing. Although some patients are able to tolerate alternative hair dyes, caution is needed as the risk of developing an allergy to other hair dye ingredients, especially PTD, is high.

Apoptosis induced by para-phenylenediamine involves formation of ROS and activation of p38 and JNK in chang liver cells.

para-Phenylenediamine (p-PD) is a suspected carcinogen, but it has been widely used as a component in permanent hair dyes. In this study, the mechanism of p-PD-induced cell death in normal Chang liver cells was investigated. The results demonstrated that p-PD decreased cell viability in a dose-dependent manner. Cell death via apoptosis was confirmed by enhanced DNA damage and increased cell number in the sub-G1 phase of the cell cycle, using Hoechst 33258 dye staining and flow cytometry analysis. Apoptosis via reactive oxygen species generation was detected by the dichlorofluorescin diacetate staining method. Mitogen-activated protein kinase (MAPK) activation was assessed by western blot analysis and revealed that p-PD activated not only stress-activated protein kinase (SAPK)/c-Jun N-terminal kinases (JNK) and p38 MAPK but also extracellular signal-regulated kinase (ERK). Cytotoxicity and apoptosis induced by p-PD were markedly enhanced by ERK activation and selectively inhibited by ERK inhibitor PD98059, thus indicating a negative role of ERK. In contrast, inhibition of p38 MAPK activity with the p38-specific inhibitor SB203580 moderately inhibited cytotoxicity and apoptosis induction by p-PD. Similarly, SP600125, an inhibitor of SAPK/JNK, moderately inhibited cytotoxicity and apoptosis induced by p-PD, thus implying that p38 MAPK and SAPK/JNK had a partial role in p-PD-induced apoptosis. Western blot analysis revealed that p-PD significantly increased phosphorylation of p38 and SAPK/JNK and decreased phosphorylation of ERK. In conclusion, the results demonstrated that SAPK/JNK and p38 cooperatively participate in apoptosis induced by p-PD and that a decreased ERK signal contributes to growth inhibition or apoptosis.

Reductive carbon dots for reduction, ratiometric fluorescence determination, and intracellular imaging of Au3.

Many studies show that ortho-phenylenediamine (OPD) produces an oxidized fluorescent product when exposed to an oxidizing agent that enables the direct or indirect fluorescence detection of a range chemical and biochemical analytes. However, there is no report on this unique optical behavior for other two isomers of phenylenediamine. This study demonstrates that a simple hydrothermal treatment of para-phenylenediamine (PPD) in the presence of sulfuric acid results in the formation of fluorescent N, S-doped carbon dots (CDs) with triple functionalities including the reduction of Au3+ into gold nanoparticles (AuNPs), the stabilization of the produced AuNPs, and the determination of Au3+ concentration through an intrinsic ratiometric fluorescence signal. In the presence of Au3+, the blue emission of CDs at 437 nm quenched, and a green emission at 540 nm emerged. The linear concentration range for the determination of Au3+ was 20 nM-16 µM with a detection limit of 16 nM. Additionally, the dual emissive CDs-AuNPs hybrid probe showed potential for the indirect fluorescence ratiometric determination of cysteine and sulfide ions. The linear concentration range for cysteine and sulfide ions were 0.25-8 µM and 0.1-6 µΜ, with detection limits of 0.095 µM and 0.041 µM, respectively. Accordingly, CDs were applied to detect Au3+ and S2- in real water samples. Moreover, the synthesized CDs showed no cytotoxicity for HeLa cells up to 300 µg mL-1, as determined by the MTT assay. Therefore, their potential for intracellular imaging of Au3+ in living cells was also investigated.

Hair Product Allergy: A Review of Epidemiology and Management.

Allergy to hair products is an increasingly common issue among people given the exposure to these products on a daily basis. Allergic reactions could be in the form of delayed-type contact dermatitis or the form of immediate-type hypersensitivity reactions. Hair products contain many ingredients and chemicals that patients may have allergies to, but common allergens are hair dyes, fragrances, persulfate salts, ammonium thioglycolate, coconut fatty acid derivatives, and acrylates. Allergy to hair dye is the most common followed by other allergens such as fragrances and persulfate salts. We discussed testing for hair dye allergy along with suggestions for alternative hair dyes that patients may use. Allergy to topical scalp medications is also seen in patients using those products. Allergy to topical minoxidil is seen more often due to the increased use of minoxidil sprays and foams among patients to increase hair growth. We will discuss in this review the diagnosis and alternatives for patients with minoxidil allergy. Hairdressers are at higher risk of allergy to hair products compared to the general population due to prolonged exposure to allergens and specific measures should be implemented to minimize the hazards of exposure.

UV-induced photodegradation of emerging para-phenylenediamine quinones in aqueous environment: Kinetics, products identification and toxicity assessments.

Substituted para-phenylenediamine quinones (PPD-quinones) are a class of emerging contaminants frequently detected in the aqueous environment. One of them, N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-Q), was found to cause acute toxicities to aquatic species at extremely low environmental levels. The ubiquitousness and ecotoxicity of such pollutants underscore the importance of their transformation and elimination. In this work, we demonstrated effective removals of five PPD-quinones in aqueous environments under UV irradiation, with up to 94% of 6PPD-Q eliminated after a 40-min treatment. By applying high-resolution mass spectrometry (HRMS) non-targeted screening in combination with isotope labeling strategies, a total of 22 transformation products (TPs) were identified. Coupling with the time-based dynamic patterns, potential transformation mechanisms were identified as an •OH-induced photocatalysis reaction involving bond cleavage, hydroxylation, and oxidation. Computational toxicity assessment predicted lower aquatic toxicity of the TPs than their parent PPD-quinones. Our results in parallel evidenced an obvious reduction of PPD-quinones accompanied by the presence of their TPs in the effluent after UV disinfection in real municipal wastewater. This work builds a comprehensive understanding of the fate, transformation products, and related toxicological characteristics of emerging PPD-quinone contaminants in the aqueous environment.

Erythematous Linear Lesion on the Course of Superficial Fibular Nerve After the Topical Application of Black Henna: A Case Report.

Henna is commonly used in body arts, where it produces orange-brown color. It is often mixed with chemicals such as para-phenylenediamine (PPD) to fasten the dyeing process and produce a black color. However, PPD has many allergic and toxic effects. We present a case of henna-induced cutaneous neuritis, which is not reported before. A 27-year-old female presented to our hospital, complaining of pain in her left great toe after applying black henna. Upon examination, the proximal nail fold was inflamed, and an erythematous non-palpable tender lesion was noticed on the dorsum of the foot. The lesion had an inverted-Y shape that was confined to the course of the superficial fibular nerve. Cutaneous nerve inflammation was favored after excluding all the anatomical structures in the region. Black henna should be avoided since it contains PPD, which can be absorbed through the skin and affect the underlying cutaneous nerves.