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Administrative data

Description of key information

Repeated Dose Toxicity:
- NOAEL oral: 10000 ppm > ca. 550 mg/kg bw/day (112 days)
- NOAEL dermal: 300 mg/kg bw/day (28-54 days)

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
550 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
300 mg/kg bw/day
Study duration:
subacute
Species:
rat

Additional information

The oral repeated dose toxicity was evaluated in a study, where a mixture of 3,7-dimethyl-2,6-octadienol and 3,7-dimethyl-1,6-octadienol was feed to five male and five female individually housed Osborne-Mendel rats per dose group (Hagan, 1967). Thereby, a concentrations of 1000 (= ca. 55 mg/kg bw/day) was administered for 189-169 days and a concentration of 10000 ppm (= ca. 550 mg/kg bw/day) was given for 112 days. During the study, the food consumption was monitored and blood was collected at the end of study and was subjected analysis of white cell counts, red cell counts and hemoglobin and hematocrit content. Also, animals were necropsied and histopathology was performed. Since no clinical signs, no effects on body weight as well as no histopathological changes were observed, the NOEL could be estimated as 10000 ppm. Thus the NOAEL would be > 550 mg/kg bw/day.

In another study, ten rats per dose were fed with 0.1% geraniol for 28 weeks and with 1% for 16 weeks (FDA, 1954). Since no effects were reported, a NOEL of 1% could be estimated. However, this data could not be considered for assessment since only concentrations of 1% and 0.1% were used and only limited data were given.

In an inhalative repeated-dose toxicity study, eight complex fragrance mixtures consisting of approximately 200 ingredients (close to one-half of the ingredients present at a level of 1% or more) were tested (Fukayama, 1999). Geraniol was present in 3 out of the eight mixtures and was tested in Syrian hamster and CD and Sprague-Dawley rats. They were whole-body exposed to the mixtures at 5, 9 or 50 mg/m³ for 4 h/day, 5 days/week for 6 or 13 weeks. The concentrations of fragrance in the chamber used were monitored and the found particle size ranged from 0.5 to 4.3 µm. Thereby, the highest determined exposure levels were 5.7 and 37.8 µg/m³. No gross pathological or histopathological findings related to test material exposures were observed. However, because different mixtures of substances were used in this study, the data could not be taken into account for assessment.

Geraniol Extra was administered via dermal administration to groups of 10 male and 10 female Wistar rats (F0 animals) at dose levels of 0 (vehicle control; test group 0), 50 (test group 1), 150 (test group 2) and 450 mg/kg bw/d (test group 3) in order to observe the possible effects of the test substance on the integrity and performance of the reproductive system in both sexes. Due to severe dermal findings, the dose level for test group 3 was decreased to 300 mg/kg bw/d from study day 10 onwards. Regarding clinical examinations, only signs of local dermal toxicity were observed for males and females at all dose levels. No changes in food consumption and body weight data were seen at any dose level. Fertility indices for male and female animals as well as development of the offspring were not impaired by test-substance administration. Regarding pathology, there were no treatment-related necropsy or histological findings in ovaries, testes or epididymides associated with dermal administration of the test substance. The local minimal inflammatory reactions in the skin of treated males (test groups 1-3) and females (test group 3 only) were regarded as related to treatment and adverse.


Repeated dose toxicity: dermal - systemic effects (target organ) other: skin

Justification for classification or non-classification

Based on the results from repeated dose toxicity testing no classification for specific target organ toxicity after repeated exposure is warrented according to Regulation (EC) No 1272/2008.