https://ntp.niehs.nih.gov/go/tr604abs

Abstract for TR-604

Toxicology and Carcinogenesis Study of Triclosan Administered Dermally to B6C3F1/N Mice

CASRN: 3380-34-5
Chemical Formula: C12H7Cl3O2
Molecular Weight: 289.55
Synonyms/Common Names: 2,4,4-Trichloro-2-hydroxydiphenyl ether; 2,4,4′-trichloro-2′-hydroxydiphenyl ether; trichloro-2′-hydroxydiphenyl ether
Report Date: May 2024

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Abstract

Two-year study in mice

Triclosan is a broad-spectrum antimicrobial agent to which humans are widely exposed. Very limited data are available regarding the dermal toxicity and the carcinogenic potential of triclosan. In this study, groups of 48 male and 48 female B6C3F1/N mice were untreated or were dermally administered 0 (vehicle), 1.25, 2.7, 5.8, or 12.5 mg triclosan/kg body weight/day (mg/kg/day) in 95% ethanol, 7 days per week for 2 years. Vehicle control animals received 95% ethanol only; untreated, naive control mice were not dosed. There were no significant differences in survival among the groups. The highest dose of triclosan decreased the body weights of mice in both sexes, but the decrease was ≤8%.

Minimal to mild epidermal hyperplasia (males and females), suppurative inflammation (males only), and ulceration (males only) were observed at the site of application in the dosed groups, with the highest incidence occurring in the 12.5 mg/kg/day groups. In male and female mice, no skin neoplasms were identified at the site of application. In male mice, the two highest dosed groups (5.8 and 12.5 mg/kg/day) had significantly increased incidences of hepatocellular carcinoma, and the incidences occurred with a positive trend relative to the vehicle control group. A positive trend in the incidence of hepatocellular adenoma or carcinoma (combined) was observed in male mice, with significantly increased incidences in the ≥2.7 mg/kg/day group. Female mice had a positive trend in the incidence of pancreatic islet adenoma.

Conclusions

Under the conditions of this 2-year dermal study, there was some evidence of carcinogenic activity of triclosan in male B6C3F1/N mice based on the increased incidences of hepatocellular adenoma or carcinoma (combined). There was equivocal evidence of carcinogenic activity of triclosan in female B6C3F1/N mice based on higher occurrences of pancreatic islet adenomas.

Dermal administration of triclosan resulted in increased incidences of nonneoplastic epidermal lesions at the site of application in male and female mice.

National Toxicology Program (NTP). 2024. NTP technical report on the toxicology and carcinogenesis study of triclosan (CASRN 3380-34-5) administered dermally to B6C3F1/N mice. Research Triangle Park, NC: National Toxicology Program. Technical Report 604. https://doi.org/10.22427/NTP-TR-604

Studies

Summary of the Two-year Carcinogenesis Study of Triclosan
  Male
B6C3F1/N Mice
Female
B6C3F1/N Mice
Dermal dose in ethanol [Untreated control group], 0, 1.25, 2.7, 5.8, or 12.5 mg/kg/day [Untreated control group], 0, 1.25, 2.7, 5.8, or 12.5 mg/kg/day
Survival rates [31/48], 35/48, 30/48, 34/48, 28/48, 31/48 [33/48], 35/48, 29/48, 31/48, 37/48, 35/48
Body weights Dosed groups within 10% of the vehicle control group Dosed groups within 10% of the vehicle control group
Nonneoplastic effects

Skin, site of application: epidermis, hyperplasia ([2/48], 1/48, 3/48, 20/48, 17/48, 43/48); epidermis, inflammation, suppurative ([2/48], 0/48, 3/48, 2/48, 4/48, 9/48); epidermis, ulcer ([2/48], 0/48, 2/48, 1/48, 2/48, 5/48)

Skin, site of application: epidermis, hyperplasia ([1/48], 0/48, 5/48, 7/48, 10/48, 39/48)

Neoplastic Effects Liver: hepatocellular adenoma ([26/48], 25/48, 30/48, 34/48, 31/48, 26/48); hepatocellular carcinoma ([27/48], 15/48, 17/48, 20/48, 25/48, 27/48); hepatocellular adenoma or carcinoma (combined) ([41/48], 31/48, 35/48, 40/48, 42/48, 40/48) None
Equivocal findings None Pancreas: islets, adenoma ([0/48], 1/48, 0/48, 0/48, 0/48, 3/48)
Level of evidence of carcinogenic activity Some evidence Equivocal evidence