Registration Dossier

Toxicological information

Exposure related observations in humans: other data

Administrative data

exposure-related observations in humans: other data
Type of information:
experimental study
Adequacy of study:
supporting study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Scienitifically acceptable publication

Data source

Reference Type:
Human Exposure to Triclosan via Toothpaste does not change CYP3A4 Activity or Plasma Concentrations of Thyroid Hormones
Allmyr M, Panagiotidis G, Sparve E, Diczfalusy U, Sandborgh-Englund G
Bibliographic source:
Basic & Clinical Pharmacology & Toxicology, 105: 339–344

Materials and methods

Type of study / information:
Clinical human study for investigatation of hormonal and enzyme system changes following in vivo exposure to triclosan.
Endpoint addressed:
repeated dose toxicity: oral
Test guideline
no guideline followed
GLP compliance:
; not applicable

Test material

Details on test material:
Toothpaste containing 0.3% (w/w) triclosan


Ethical approval:
other: The study was approved by the ethics committee at Karolinska Institute, Huddinge, Sweden; Dnr 2008 ⁄ 615-31.
Details on study design:
Twelve healthy adults, five men and seven women, were recruited for the study; the participants were employees or students at Karolinska Institute, Huddinge, Sweden and written informed consent was mandatory for participation in the study.
The participants were considered healthy by standard physical examination and routine laboratory tests. Exclusion criteria were ongoing or within the previous 2 months ended medication, use of prescription free drugs (e.g. St John’s wort), and positive test for pregnancy. The half-life for triclosan in plasma is 19 hr and the authors had previously shown that plasma concentrations return to baseline levels within 8 days after exposure to triclosan. Hence, the participants admitted to set out any personal triclosan-containing products 2 weeks before and during the experimental exposure to triclosan toothpaste. In addition, the intake of any products containing grapefruit, which is known to inhibit CYP3A4 activity, was avoided.
Exposure assessment:
Details on exposure:
The participants were instructed to brush their teeth for 3 minutes with a 2 cm strain of a toothpaste containing0.3% (w w) triclosan twice a day (morning and evening) for 14 days. These criteria were estimated, and selected with the objective to reflect an upper range of exposure to triclosan via toothpaste that may be expected in a normal human population. No toothpaste was to be swallowed on purpose. For compliance control, the participants logged the time for each occasion they brushed their teeth.

The blood samples were collected at the Karolinska University Hospital, Huddinge, Sweden. One blood sample was collected from each participant at two occasions; one the day before the start of exposure and one the day after the end of exposure. Blood was centrifuged and the plasma was transferred to polypropylene tubes for storage at- 20°C immediately after sampling until analysis.

After sample hydrolysis, triclosan was determined as the sum of triclosan present in unconjugated and conjugated form. Triclosan was analysed using liquid-liquid extraction. An isotope dilution method with 13C-labelled triclosan as the internal standard was applied for quantification, using gas chromatography ⁄ electron capture negative ionisation ⁄mass spectrometry (Allmyr et al., Anal Chem 78:6542–6546, 2006).
4ß-Hydroxycholesterol was determined by isotope dilution gas chromatography-mass spectrometry using a deuterium-labelled internal standard.
Thyroid hormones (FT3, FT4 and TSH) were determined by commercial electrochemiluminescence immunoassays (Roche Diagnostics GmbH, Mannheim,Germany).

Results and discussion

Triclosan in plasma:
The triclosan concentrations were above the limit of quantification in all analysed plasma samples. The plasma triclosan concentrations were significantly higher after than before the 14 days of exposure to triclosan containing toothpaste. Before exposure, the triclosan concentrations ranged from 0.009 to 0.81 ng ⁄ g whereas after exposure, the concentrations ranged from 26 to 296 ng ⁄ g; the difference was statistically significant (one-tailed paired t-test; p = 0.003).

4ß-Hydroxycholesterol, thyroid-stimulating hormone, free thyroxine and free tri-iodothyronine in plasma:
There were no significant differences in plasma concentrations before and after the exposure to triclosan contained in toothpaste for any of the analysed variables. FT3, FT4 and TSH concentrations were all within the reference interval (FT3: 3.0–6.5 pmol ⁄ l; FT4: 12–23 pmol ⁄ l; TSH: 0.4–4.7 mE/l).

Applicant's summary and conclusion