Update on occupational dermatitis: reviewing toxic substances from OSHA standards

Abstract

Occupational dermatitis (OD) is an inflammatory skin disease stemming from exposure to specific substances within a work setting. As the second most prevalent occupational health concern in 2020, affecting 1.8 per 10,000 workers, OD poses a significant challenge to workforce well‐being and imposes a substantial economic burden through lost wages, decreased productivity, and increased healthcare spending. Dermatologists emerge as pivotal figures in recognizing risk factors and delivering essential care to individuals with OD. This review focuses on chemical hazards and toxic substances regulated by the Occupational Safety and Health Administration across general industry, maritime, and construction sectors. It explores the background of each hazard, pathophysiology to dermatitis, and human cases reported between 2017 and 2023 for formaldehyde, chromium, vinyl chloride, and cadmium.

Background

Occupational dermatitis (OD) is an inflammatory skin disease caused by exposure to certain products in a work setting. It is a common occurrence, with an estimated prevalence between 10% and 17%. ¹ , ² OD is split into two forms: irritant contact dermatitis and allergic contact dermatitis (ACD). Research suggests that over 90% of OD falls under contact dermatitis (CD), the majority of which affects the hands. ³

In 2020, the United States Bureau of Labor Statistics reported that occupational hand dermatitis (OHD) had an incidence rate of 1.8 per 10,000 workers, making it the second most common occupational health concern. ⁴ Moreover, a large economic burden is attached to OD. In 2013, CD was estimated to cost the United States $1.5 billion. ⁵ Financial costs can be incurred due to lost wages, productivity, and healthcare spending. In the United States, the Occupational Safety and Health Administration (OSHA) has established standards for regulating chemical hazards and toxic substances to protect workers.

This review examines toxic substances listed in the OSHA Standards for general, maritime, and construction industries. ⁶ We provide background information on each hazard, pathophysiology to dermatopathology, and relevant literature regarding its association with dermatological conditions, focusing on dermatitis.

Methodology

We conducted a systematic literature review using PubMed, focusing our search on occupational exposures that specifically caused dermatitis in our review. The search terms (occupation OR occupational OR work OR worker OR profession OR professional) AND “dermatitis” AND [exposure] were used, with [exposure] including toxic chemicals from the OSHA Toxic Chemical Standards separated by the OR statement. These chemicals included “(air pollution OR air particulate OR air contaminant)” OR “asbestos” OR “vinyl” OR “arsenic” OR “lead” OR “chromium” OR “cadmium” OR “benzene” OR “acrylonitrile” OR “ethylene oxide” OR “formaldehyde” OR “methylenedianiline” OR “1,3 butadiene” OR “methylene chloride.”

Only articles that included human studies and review articles between 2017 and 2023 were included for review. Due to access limitations, only English studies were included. Animal studies, conference presentations, and abstracts were not included for review. After limitations were applied, a total of 279 article titles and abstracts were reviewed for relevance, after which 159 articles were left for full‐text review. Articles were excluded if they did not discuss an occupational hazard, a chemical of interest, or a dermatological condition of interest. After a full‐text review, 63 articles published between 2017 and 2023 remained. Only chemicals with five or more articles after filters were applied were included in this article. In addition, supplementary articles from certified government or research agencies were included to provide toxicological information.

Formaldehyde

Formaldehyde (FA) is a colorless gas with a distinct odor when used at room temperature. It is useful for its antimicrobial and preservative properties. Sensitization to FA has been estimated to be 8%–9% in the US and 2%–3% in Europe. ⁷ , ⁸ However, studies have documented a downtrend in FA contact allergy from 2007 to 2016. ⁹ , ¹⁰ FA occupational exposure primarily arises through three key channels: in FA production, manufacturing items containing FA, and the combustion of products that release FA. ¹¹ The top occupations at risk of FA‐induced OD are manufacturers, healthcare workers, and personal/household services. ¹² , ¹³ , ¹⁴

The precise pathophysiology of FA‐induced dermatitis is not fully understood. Patch tests have shown that positive reactions to FA are associated with FA‐releasing substances, though instances of the reverse are rare. ¹⁵ , ¹⁶ Studies by Ma et al. suggest that FA might activate the nucleotide‐binding domain, leucine‐rich–containing family, pyrin domain‐containing‐3 (NLRP3) inflammasome in macrophages, leading to the induction of ACD in mice. ¹⁷ Additionally, Mai et al. conducted a study comparing circulating interleukin‐17 (IL‐17) and IL‐22 levels in workers exposed to low‐level FA and non‐exposed controls, concluding that IL‐17 and IL‐22 may play a role in OACD. ¹⁸

Workers may encounter FA exposure from resins, building materials, preservatives, and combustion byproducts in manufacturing. Dermatologic sensitization to FA has been extensively documented in production workers. ¹⁴ In North America, FA is a prominent OD allergen for production workers, commonly arising from adhesives/glues, metalworking fluids/cutting oils, and coatings. ¹⁹ A retrospective study conducted by Schubert et al. revealed a higher incidence of sensitization to FA and FA releasers in cutting metalworkers compared to mechanics or other metalworkers. ²⁰ Notably, a case of OACD in a worker within the food packaging industry worker resulted from FA resin from the food can coating. ²¹ Certain regions have a concerning lack of FA regulations within manufacturing. In Eastern Thailand, a patch test indicated that 5.6% of workers exposed to FA levels exceeding the OSHA standards tested positive for OD. ²² This underscores the importance of addressing regulatory gaps to safeguard the health and well‐being of workers in industries where FA exposure is prevalent.

In the healthcare sector, FA is present in preservatives, disinfectants, personal protective equipment (PPE), and adhesives. A study conducted in Finland from 2005 to 2016 noted that FA was the second most frequent cause of ACD related to preservatives among healthcare workers. ²³ Henning et al. reported that 11.5% of physicians experienced CD attributed to FA, likely stemming from their use of disinfectants. ²⁴ During the Coronavirus pandemic, the widespread adoption of masks and PPE led healthcare workers to experience higher incidences of ACD, as reported in multiple studies. ²⁴ , ²⁵ , ²⁶ , ²⁷ Specific professional groups within healthcare may have more frequent FA exposures. For example, FA resin found in shoe insoles increases podiatrists' exposure to FA. ²⁸ This increased prevalence of FA‐containing materials in the healthcare setting underscores the need for enhanced awareness and preventive measures.

In personal/household services, FA is found in disinfectants and cleaning products. Regular exposure to disinfectants and soaps containing FA releasers can compromise the skin barrier, facilitating the penetration of FA present in personal and cleaning products. ⁷ Although OD is generally more reported in males, FA‐induced ACD is frequently noted in women exposed to cleaning products, manifesting as AD on their hands and/or face. ⁷ , ²⁹ A retrospective study conducted by Melo et al. from 2000 to 2014, analyzing OACD in Brazil, revealed that FA‐induced OD was most commonly observed in cleaners. ³⁰ This heightened sensitization, even with gloves, may be attributed to the fact that single‐use gloves, frequently utilized in cleaning tasks, are susceptible to chemical penetration and do not provide a sufficient barrier to the skin. ³¹ This emphasizes the importance of recognizing and addressing the occupational risks of FA exposure in the personal and household services sector and modifying PPE for cleaners to provide adequate protection.

Chromium

Chromium (Cr) is a heavy metal element that exists in both Cr(III) and Cr(VI) forms. While Cr(III) is chemically stable and not harmful, Cr(VI) is considered allergenic. ³² Cr(VI) has been historically found in cement, leather, and electroplating, and therefore, workers at the highest risk for Cr toxicity are in the construction, tanning, and metal industries. ³³ , ³⁴ , ³⁵ Cr has been under scrutiny in the last two decades and has begun to be regulated in many countries.

The pathophysiology of chromium CD involves Cr(VI), which penetrates the skin more readily than Cr(III). However, Cr(VI) is not directly involved in inducing CD. After penetration, Cr(VI) is oxidized to Cr(III), which generates haptens that antigen‐presenting cells present to naïve T cells to form memory T cells. With subsequent exposure, increased pro‐inflammatory cytokines can lead to ACD. ³⁶ Simultaneously, Cr(VI) plays a role in activating antigen‐presenting cells that activate chromium‐specific T cells by accumulating reactive oxygen species. ³⁴ Cr allergy, once induced, is persistent and has a poor prognosis. ³⁷ , ³⁸

In construction, workers are exposed to Cr(VI) from cement. Cr(VI) in cement is derived when Cr(III) from raw materials like limestone and clay minerals is oxidized to Cr(VI) during the clinkerization process. ³⁹ Multiple cases of construction workers suffering from OHD have been reported in Taiwan, Brazil, and Turkey. ⁴⁰ , ⁴¹ , ⁴² Legislation was passed by Denmark, Sweden, and Finland in the 1980s and later by the EU to mitigate cement‐induced OD by adding ferrous sulfate to cement containing Cr, which reduces Cr(VI) without compromising the quality of concrete. ⁴³ , ⁴⁴ , ⁴⁵ The EU also set a <2 mg/kg soluble Cr(VI) limit in cement in 2005. ³⁶

Countries that regulated Cr(VI) in cement saw significant drops in cases of cement‐induced CD in construction workers ⁴⁴ compared to countries that did not, like India and Australia, ⁴⁶ , ⁴⁷ , ⁴⁸ , ⁴⁹ , ⁵⁰ although rare cases of chromium ACD in countries with regulation have been reported. ⁵¹ However, a clinical trial found that glutathione and iron sulfate‐containing barrier creams can inhibit ACD in Cr(VI) sensitized individuals. ⁵² These findings suggest that while new barrier creams may serve as solutions to those suffering from CD, legislation is an effective measure to prevent Cr‐based OACD, which can improve occupational health and allow workers to continue their role without further harm to themselves.

In the tanning industry, workers are exposed to Cr(VI) from the chrome tanning process, the most common tanning process due to its low cost and time efficiency. Insoluble Cr(III) salts are used in tanning processes, which can oxidize into Cr(VI). ⁵³ Consumers can thereby be sensitized by Cr(VI) remaining in leather. ⁴⁴ , ⁵⁴ , ⁵⁵ Cr(VI) may also be released into the water, contaminating the environment and harming individuals who encounter it. ⁵⁶ EU's Registration, Evaluation, Authorisation, and Restriction of Chemicals (REACH) has restricted Cr(VI) in leather to contain less than 3 mg/kg of total dry weight of leather. ⁵⁷ A study has found that after 5 years of the regulation against Cr(VI) in leather, there was no apparent improvement in patients with Cr allergy from leather exposure. ⁵⁸ Therefore, mitigating leather‐induced CD in workers and consumers and decontaminating wastewater from chrome‐tanning facilities are ongoing efforts that need further research and implementation.

In the metals industry, workers are exposed to Cr(VI) through chrome plating iron or zinc‐based metal items with Cr to prevent rust or surface oxidation. Chrome platers at an electroplating factory were found to have chrome ulcers most frequently in the hands, fingers, and wrist, CD, and mucosal irritation. ⁵⁹ A meta‐analysis of metal allergy in metalworkers found a relationship between chromium ACD and occupational exposures. ⁶⁰ Mobile phones and orthopedic functional implants are other recently discovered sources of Cr‐induced CD. ⁶¹ , ⁶² , ⁶³ , ⁶⁴ , ⁶⁵

Vinyl Chloride

Vinyl chloride (VC) is a synthetic polychloride used to manufacture plastics such as polyvinyl chloride (PVC). It is transported in a pressurized, liquified gaseous form, lending it high flammability. VC is an International Agency for Research on Cancer (IARC) Group 1 carcinogen known to cause hepatic angiosarcoma and neurological, developmental, immunological, and dermatological side effects. Occupational exposure comes from workers involved in the manufacturing, utilization, transportation, and disposal of VC used in PVC.

The pathophysiology of VC‐induced dermatitis has been associated with increased exposure to oxidative stress and inflammatory cytokines such as tumor necrosis factor‐α (TNF‐α), IL‐1, IL‐6, and IL‐8, which can lead to fibrosis, as seen in acute and chronic inflammation. ⁶⁶ , ⁶⁷ Chronic inflammation from VC is linked to cutaneous carcinomas by polymorphisms in cytochrome P450 2E1 (CYP2E1) that lead to reactive intermediaries and increased mutant biomarkers ras‐p21 and p53. ⁶⁸ It is important to note that VC exposure is predominantly through inhalation or oral exposure, with a minimum risk level (MRL) of 0.02 ppm (≤14 days) for acute inhalation and 0.003 ppm for chronic (≥365 days) oral exposure. ⁶⁹ Afterward, VC is absorbed into the bloodstream via the lungs of the stomach and distributed throughout the body. ⁶⁹ VC is then metabolized by cytochrome P450 (CYP) enzymes in the liver before being excreted primarily through the urine with an estimated half‐life of around 1 h. ⁶⁹

Acute cutaneous exposure to VC may cause CD, frostbite, erythema, blistering, and desquamation. ⁶⁹ There have also been rare reports of dermatitis in workers using PVC gloves who tested positive for triphenyl phosphite (TPP), a component of PVC antioxidants. ⁷⁰ , ⁷¹ In addition, there have been reports of dermatologic risk after mass exposure to VC following chemical spills. Of 231 emergency department visits directly related to a VC spill in 2021, 5.1% of the patients had dermatological symptoms. ⁶⁷ , ⁷² First responders and workers involved in cleaning up chemical spills are especially at a higher risk of exposure. Chronic exposure to VC may lead to the development of VC disease, including sclerotic skin changes predominantly affecting the hands, Raynaud's, and lytic bone lesions. ⁶⁶ , ⁶⁷

Chemical protective personal equipment, including respirators, and prompt decontamination after exposure are important in reducing occupational exposure to VC. Additionally, noting geographic exposures to VC due to manufacturing plants or environmental spillage could delineate high‐risk regions for future skin cancer screenings. ⁶⁷

Cadmium

Cadmium (Cd) is a metal element naturally found in the environment in air, soil, and water. It is predominately used in industry for manufacturing batteries, plastics, coloring agents, metals, and electrical recycling. ⁷³ In 2012, Cd was labeled an IARC Group 1 carcinogen for sufficient evidence of carcinogenicity in humans, leading to lung, renal, and prostate carcinomas. ⁷⁴ While Cd exposure can occur in low levels through diet and tobacco smoking, occupations at risk of Cd toxicity are manufacturing batteries, plastics, and metal smelting.

The pathophysiology of Cd‐induced dermatitis is thought to be through cytotoxic and inflammatory mechanisms. Cd exposure can occur through oral and respiratory routes. In the occupational setting, Cd's main route of exposure is through inhalation. After inhalation, Cd is distributed through the bloodstream via metallothionein and accumulates in the liver, gastrointestinal tract, and kidneys. It has a long half‐life that ranges from 7 to 16 years. ⁷⁴ Once absorbed, Cd can accumulate intracellularly, generating reactive oxygen species and inflammatory cytokines. Chronic exposure to Cd has been linked to the upregulation of inflammatory markers, such as IL‐6, TNF‐α, IL‐1β, IL‐8, and C‐reactive protein (CRP). ⁷⁵ Cd toxicity may impair zinc absorption; deficiency of this mineral has been postulated to contribute to dermatitis. ⁷⁶

Cd's role as an occupational skin sensitizer and trigger for CD is controversial. ⁷⁷ Limited case studies or cohort studies have been published on this topic in the last few decades. This corresponds with the IARC, which noted decreased occupational exposure to Cd since the 1970s. ⁷⁸ One cross‐sectional study on heavy metal exposure and OHD noted that those with active OHD had higher blood levels of lead and Cd—although no association of OHD and Cd was seen in multivariate logistic regression. ⁷⁹ More recently, the connection between prenatal exposure to heavy metals such as Cd and childhood ACD has been established. A Taiwanese study of 1152 pregnant mothers noted exposure to arsenic and Cd may increase the odds of children developing ACD by the age of 4, although this association was more strongly associated with arsenic exposure. ⁸⁰ A prospective study conducted in 637 mother‐children pairs noted children with elevated cord Cd levels have 2.35 higher odds of developing ACD. ⁸¹ However, while increased Cd in maternal subjects may have been attributed to occupational exposure, the exact source was not determined in these studies.

Cd has also been related to other dermatological diseases. A cohort study of nearly 6000 patients noted higher levels of serum Cd, which corresponded with psoriasis patients and more severe psoriasis. ⁷⁵ While the source of Cd was not clearly outlined, the authors note that occupational exposure is the most common cause of elevated Cd levels. ⁷⁵ This is important for pregnant patients who work in settings where Cd exposure may be high. Patients with ACD or psoriasis who work in industries with Cd should also consider increased PPE to protect themselves from potential aggravation of their disease, and patients who are pregnant or planning to become pregnant should be advised by their physicians of potentially harmful exposures in the workplace.

Conclusion

This review underscores the impact of exposure to toxic chemicals and hazardous substances in the workplace, which is set by OSHA guidelines and has led to the development of OD. Regulatory efforts such as OSHA in the United States and REACH in the European Union have been crucial in limiting exposure to these harmful substances. These regulations have played a pivotal role in protecting workers, reducing OD cases, and mitigating the economic burden associated with these dermatological conditions. ⁴⁴ , ⁴⁶ However, the lack of consistent global standards and enforcement highlights the need for continued international collaboration and advocacy to ensure further protection for workers worldwide. ⁴⁷ , ⁴⁸ , ⁴⁹

Efforts to address the complexities of OD should extend beyond regulatory frameworks. Healthcare providers play a pivotal role in assisting patients in recognizing and avoiding potential triggers in their workplaces. Given the close correlation between exposure and socioeconomic status, ⁸² , ⁸³ health justice emerges as a crucial component of advocacy efforts. Prioritizing equitable access to information and personal protective measures becomes imperative to address disparities in occupational health outcomes. By emphasizing health justice, we can strive for a more inclusive and comprehensive approach to safeguarding the well‐being of workers.

Physicians should remain cognizant of the historical and present risks faced by workers, which are constantly evolving with new regulations and industry changes. This awareness is paramount in guiding preventive measures, early detection, and effective management of OD. The collective commitment of regulatory bodies, healthcare providers, and advocates is essential to fostering a global culture of workplace safety and health justice, ultimately ensuring the well‐being of workers across diverse industries and regions.