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Key value for chemical safety assessment

Additional information

Background

Mandarin 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, mandarin oil is part of the particular category of essential oils, extracts, fractions and distillation products of the citrus species of chapter 1.2, which are all variants of the botanical Rutacae family. A justification for read across within this category can be found in the “Reporting format for Natural Complexe Substances of the Citrus essential oils of the Rutacae family”. The other members of this category are orange oil, lemon oil, lime oil, grapefruit oil, bitter orange oil, and tangerine oil. The category is based on the part of the plant from which the NCSs are produced (pericarb of the fruit), the common methods of production, the same dominant constituent (limonene), and the same and/or similar constituents.

 

The toxicokinetics assessment of the citrus oils will be based on the toxicokinetic assessment of dominant constituent limonene. For the other constituents, physical/chemical parameters will be used to determine whether absorption via the oral, inhalation, and dermal route is expected.

 

Limonene

For limonene, the main route of excretion of d-limonene is via urine (75-95% of the dose orally administered). Faecal excretion accounts for less than 10% of the dose. When dermally administered, urine is again the main route of excretion, but almost half the administered dose is recovered by skin washing after exposure.

Furthermore, in a review done by the National Institute of Occupational Health in(Karlberg A.T. and Lundell B., 1993, Limonene, Beije B., Lundberg P. (eds). Criteria documents from the Nordinc Expert group. Arbete och Habsa, 35, 1 -254, the following information is mentioned:

- distribution: after absorption, d-limonene disappears rapidly from blood. This is mainly due to distribution to different tissues and the biotransformation. The blood clearance in human after exposure has been determined to 1.1 L/kg x hour. A high solubility of d-limonene in olive oil (calculated partition coefficient oil/blood = 140) as well as a long half-life in blood, in the slow elimination phase, indicate affinity to adipose tissues. Species differences in renal disposition and protein binding of d-limonene were observed.

- biotransformation: there are some different pathways in the metabolism of d-limonene among the various species explored, including oxidation at the 8,9 -double bond or the 1,2-double bond, oxidation of the methyl groups to hydroxyl and further to carboxylic acid derivatives, ring hydroxylaion at the C-1 and C-6 position, and glycine or glucuronide conjugation. Species differences in plasma and urinary metabolites were observed.

- excretion: 3 different phases of elimination of d-limonene were observed in human blood. The half-lifes in blood after exposure by inhalation for 2 hours to 450 mg d-limonene/m3 were ca. 3 min, 33, min and 750 minutes. D-limonene seems to be metabolised to a very large extent.

 

Other 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 other constituents of mandarin oil.

 

Constituent

Molecular weight

Water solubility (mg/l at 25°C)

Log Kow

Vapour pressure (Pa at 25°C)

α-Pinene

136.24

3.4834

4.27

536

α-Thujene

136.24

3.4834

4.61

655

ß-Pinene

136.24

2.6192

4.35

334

γ-Terpinene

136.24

59.034

4.75

153

Myrcine B

136.24

17.814

4.88

320

Terpinolene

136,24

93,066

4.88

133

 

Although, based on vapour pressure, all constituents have a low volatility (<0.5 KPa), exposure via inhalation is included based on the use of orange oil as a fragrance. Oral absorption and absorption via inhalation may be low for these substances, based on their low to moderate water solubility and log Kow >4. Dermal absorption is not favoured based on the molecular weights of the substances, and based on the log Kow >4 and low to moderate water solubility, it is expected to be low to moderate.

 

Conclusion

The major constituent of mandarin oil, limonene, is expected to be readily absorbed by the oral and inhalation route. Dermal absorption is assumed to be lower, however, as no information is available on the amount of dermal absorption, it is assumed to be similar to oral absorption as a worst case. For the other constituents of mandarin oil, the absorption via the oral, inhalation and dermal route is expected to be low to moderate.

For risk assessment, oral and dermal absorption are assumed to be similar (100%). In absence of information on the inhalation route, a default absorption of twice the oral absorption is assumed for inhalation absorption.