Tolylene-2,4-diisocyanate: Dermal Exposure and carcinogenicity

General Description

The assessment of dermal exposure to Tolylene-2,4-diisocyanate presents challenges due to limited data and varying reported exposures, exacerbated by uncertainties in historical personal protective equipment (PPE) usage. While Tolylene-2,4-diisocyanate-induced respiratory effects, particularly sensitization leading to asthma, are documented in workers, diagnosing occupational asthma remains problematic without specific bronchial provocation challenges. Animal studies, primarily involving Brown Norway rats, have elucidated respiratory sensitization mechanisms but suggest minimal dermal absorption and low risk of respiratory sensitization from dermal exposure alone. Additionally, carcinogenicity studies in rodents indicate increased tumor incidences, particularly in orally exposed subjects, possibly linked to metabolites like 2,4-TDA. However, uncertainties persist regarding dose-response relationships and relevance to human health. Overall, while Tolylene-2,4-diisocyanate exposure may pose risks of respiratory and carcinogenic effects, further research is crucial to fully comprehend its implications for occupational health and safety.

Figure 1. Tolylene-2,4-diisocyanate

Dermal Exposure

Tolylene-2,4-diisocyanate is primarily evaluated for inhalation exposure risks, but there's growing concern regarding potential health effects from dermal exposure. However, quantifying dermal exposure to Tolylene-2,4-diisocyanate is challenging due to a lack of data, and reported exposures vary widely. Additionally, changes in personal protective equipment (PPE) usage over time further complicate the assessment, as the prevalence of glove use is often unknown. Studies examining TDI-induced respiratory effects suggest a sensitization response, with some workers developing TDI-induced asthma. However, definitive diagnosis of occupational asthma (OA) is hindered by the absence of bronchial provocation challenge with Tolylene-2,4-diisocyanate. Animal studies, particularly using Brown Norway rats, are useful for identifying respiratory sensitizers and assessing the interaction between respiratory and dermal exposures. Despite concerns, research suggests that dermal absorption of Tolylene-2,4-diisocyanate is minimal (< 1%), and dermal exposure alone is unlikely to induce respiratory sensitization in animals. Moreover, studies on foam workers indicate that Tolylene-2,4-diisocyanate concentration in freshly made foam decreases rapidly, and there's limited migration from intact, cured foam. Overall, while uncertainties remain, current evidence suggests that dermal exposures may not substantially contribute to the risk of OA in Tolylene-2,4-diisocyanate workers. ¹

Carcinogenicity

Tolylene-2,4-diisocyanate is a chemical compound that has been studied for its potential carcinogenicity in animal models. Carcinogenicity and genotoxicity studies have been conducted to assess the effects of Tolylene-2,4-diisocyanate exposure on rats and mice. In a 2-year inhalation bioassay by Loeser (1983), rats and mice were exposed to Tolylene-2,4-diisocyanate vapor for a duration of 2 years, but no treatment-related carcinogenic responses were observed. However, there were increased incidences of multiple lung adenomas and lymphomas in treated male mice, although the statistical significance of these findings was debated. The study did not report similar findings in female mice or rats. In a 2-year oral gavage bioassay by NTP (1986), rats and mice were exposed to Tolylene-2,4-diisocyanate mixed with corn oil by gavage. Significant increases in the incidence of various tumor types were observed, such as lymphomas in female mice, subcutaneous tissue tumors in male and female rats, and mammary gland tumors in female rats, among others. The study did not report respiratory tract tumors in mice or rats. While the inhalation exposure study showed increased rates of multiple lung adenomas in male mice, it was noted that there was no clear dose-response relationship, and the biological significance of these findings was questioned. The oral gavage study indicated a significant increase in various tumor types, with a potential explanation being the conversion of Tolylene-2,4-diisocyanate to a related compound, 2,4-TDA, which is known to be tumorigenic in rodents. Overall, the animal studies suggest that Tolylene-2,4-diisocyanate exposure may lead to an increased risk of certain tumor types in rats and mice, although the exact mechanisms and the relevance to human health are still under investigation. Further research is needed to fully understand the carcinogenic potential of Tolylene-2,4-diisocyanate in animals and its implications for human health. ²

Reference

1. Lynch HN, Prueitt RL, Goodman JE. Critique of the ACGIH 2016 derivation of toluene diisocyanate Threshold Limit Values. Regul Toxicol Pharmacol. 2018; 97: 189-196.

2. Prueitt RL, Lynch HN, Zu K, Shi L, Goodman JE. Dermal exposure to toluene diisocyanate and respiratory cancer risk. Environ Int. 2017; 109: 181-192.