Registration Dossier

Diss Factsheets

Administrative data

Link to relevant study record(s)

Description of key information

Key value for chemical safety assessment

Additional information

Background
Peppermint oil is a substance of Unknown or Variable composition, Complex reaction products or Biological material (UVCB substances), or more specifically an NCS (Natural Complex Substance). As such, peppermint oil is part of the particular category of essential oils, extracts, fractions and distillation products of the mint species of chapter 1.2, which are all variants of the botanical Lamiaceae family, genus Mentha. A justification for read across within this category can be found in the “Reporting format for Natural Complex Substances of the Mint essential oils of the Lamiaceae family, genus Mentha”. The other member of this category is cornmint oil. The category is based on the part of the plant from which the NCSs are produced (fresh, above ground parts of the flowering plants), the common methods of production, the same dominant constituent (L-menthol and Menthone (in combination >60%)), and the same and/or similar constituents. Several publications concerning the toxicokinetics of peppermint oil are available in the dossier. Furthermore, the physical/chemical parameters of the constituents will be taken into account.

Information from experimental studies
The toxicokinetics properties of peppermint oil were examined in several in vivo human studies, as well as in vitro studies with human liver microsomes. In the in vivo studies, human volunteers were exposed to different forms of delayed-release capsules containing peppermint oil, for its use to treat irritable bowel/spastic colon syndrome. The excretion of menthol in the urine was measured after a single dose of peppermint oil to human volunteers in three different experiments. Results show a recovery of 35-40% in urine as menthol or mentholglucuronide after 24hr (Somerville et al., 1984), while in another experiment 87-112% was recovered as menthol or mentholglucuronide in urine (White, 1987). In the third study menthol was also determined in urine, however, percentage recovery could not be determined (Kaffenberger, 1990). These studies indicate that peppermint oil is absorbed after oral exposure. In vitro and in vivo experiments examining effects of peppermint oil on the metabolism of two different calcium channel blockers (nifedipine and felodipine), show that peppermint oil is a reversible, partially mixed inhibitor of metabolism of these substances both in vitro and in vivo, indicating inhibition of CYP3A4. (Dresser et al., 2002) This study indicates that metabolism of peppermint oil is expected in the human body. No information could be retrieved concerning dermal and inhalation absorption.

Physical/chemical properties of constituents
Physical/chemical parameters indicating whether absorption via the oral, inhalation and dermal route is expected, are for example molecular weight, water solubility, log Kow, and vapour pressure. Please find below a table containing these parameters for the constituents of peppermint oil.

Constituent

Molecular weight

Water solubility (mg/l at 25°C)

Log Kow

Vapour pressure (Pa at 25°C)

L-menthol

156.27

941.74

3.38

1.02

Menthone

154.25

895.86

2.87

49.4

L-limonene

136.24

44.388

4.83

193

betapinene

136.24

2.6192

4.35

334

1,8-cineole

154.25

551.66

3.13

208

Alpha-Pinene

136.24

3.4834

4.27

536

Iso-menthone

154.25

895.86

2.87

49.4

neo-menthol

156.27

941.74

3.38

1.02

Methyl acetate

198.31

53.781

4.39

12.2

Piperitone

152.24

135.01

3.07

13.8

Pulegone

152.24

212.83

3.2

21.6

Iso-Pulegol

154.25

943.2

3.37

0.662

Germacrene-D

204.36

0.81945

6.99

3.04

Neo-iso-pulgol

154.25

943.2

3.37

0.662

Octan-3-ol

130.23

1285.3

2.73

13.3

Sabinene

136.24

2.6192

4.69

981

Myrcene

136.24

17.814

4.88

320

Neo-iso-menthol

156.27

941.74

3.38

1.02

Beta-caryophyllene

204.36

0.54268

6.3

4.16

Menthofuran

150.22

47.144

4.29

10.7

trans sabinene hydrate

154,25

742,39

3,19

13,2

cis-Ocimene

136,24

38,089

4,8

358

Gamma-terpinene

136,24

59,034

4,75

153

Terpinolene

136,24

93,066

4,88

133

Although, based on vapour pressure, most constituents have a low volatility (<0.5 KPa), exposure via inhalation is included based on the use of peppermint oil as a fragrance. Oral absorption and absorption via inhalation is expected for most substances, as they have a molecular weight <500, moderate to high water solubility, and log Kow between 1-4. Substances with a log Kow>4 and with a low water solubility, such as betapinene, alpha-pinene, germacrene-D, sabinene, beta-caryophyllene, may be less well absorbed orally due to their log Kow >4 and relatively low water solubility.
Dermal absorption is not favoured based on the molecular weights of the substances, neither can it be ruled out. For the substances which have a log Kow <4 combined with a relatively high water solubility, dermal absorption is expected. For betapinene, alpha-pinene, germacrene-D, sabinene, beta-caryophyllene, which have a log Kow >4 and relatively low water solubility, dermal absorption is expected to be low to moderate.

Conclusion
Toxicokinetic studies with peppermint oil indicate that the substance is orally absorbed and metabolized. Based on physical properties of the constituents, absorption via the oral, inhalation and dermal route is expected to be moderate to high. For risk assessment, a default absorption of 100% is assumed.

Categories Display