Allergic contact sensitizing chemicals as environmental carcinogens

Area of Science:

• Toxicology
• Dermatology
• Carcinogenesis

Background:

• Chemicals causing allergic contact dermatitis (ACD) and genotoxic carcinogens share electrophilic properties, suggesting potential overlap in carcinogenic activity.
• The National Toxicology Program (NTP) has bioassayed numerous chemicals for toxicity and carcinogenicity.

Purpose of the Study:

• To evaluate the tumorigenic potential of chemicals known to cause ACD in humans.
• To assess the utility of ACD testing as a screening tool for identifying potential environmental carcinogens.

Main Methods:

• Analysis of published NTP bioassays (genotoxicity and carcinogenicity studies) available by early 1996.
• Identification of chemicals within the NTP dataset known to cause human ACD.
• Comparison of tumorigenic characteristics between ACD-positive and ACD-negative chemicals, stratified by genotoxicity.

Main Results:

• Of 209 NTP-bioassayed chemicals, 36 (17%) were known human contact sensitizers, with about half showing positive tumor bioassay results.
• Contact sensitizers included a higher proportion of nongenotoxic chemicals compared to the overall NTP sample.
• Genotoxic chemicals demonstrated stronger carcinogenicity with higher tumor incidence and induction in more organs than nongenotoxic chemicals.

Conclusions:

• Contact sensitizers, particularly nongenotoxic ones, represent a significant group of potential environmental carcinogens.
• Incorporating ACD testing alongside the Ames test could enhance the detection of non-genotoxic tumorigens by approximately 40%.
• Thousands of commercially used contact sensitizers may also be rodent tumorigens, highlighting a public health concern.