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Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via dermal route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
300 mg/kg bw/day
Species:
rat
Additional information

Geraniol Extra (CAS 106 -24 -1) 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 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.


Short description of key information:
No data is available for Citronellol, however the structurally related substance Geraniol (CAS 106-24-1) is used for read-across.
A dermal screening study acc. to OECD 421 has been performed with Geraniol. Dermal application was chosen because this is the relevant route of exposure. The only effect seen was massive skin irritation, whereas fertility and development were unaffected. This study is regarded as key study.
In addition, an oral screening study acc. to OECD 421 was done with the reaction mass of 2,6-Octadien-1-ol, 3,7-dimethyl-, (E-) and 2,6-Octadien-1-ol, 3,7-dimethyl-, (Z-), which was not regarded as relevant, since it was not performed with the pure substance but with the reaction mass and led to unclear results due to a questionable correlation of effects seen on parental animals and offspring.

Effects on developmental toxicity

Description of key information
OECD 414 (BASF SE 2016): No toxicologically relevant adverse maternal and fetal toxicity was observes. Thus, the no observed adverse effect level (NOAEL) for maternal and prenatal developmental toxicity is 750 mg/kg bw/d.
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
750 mg/kg bw/day
Species:
rat
Additional information

In a prenatal developmental toxicity study according to OECD 414 and under GLP the test substance Citronellol was administered to pregnant Wistar rats daily by gavage from GD 6 to GD 19 to evaluate its potential maternal and prenatal developmental toxicity (BASF SE 2016).

Generally, clinical observations including food consumption and body weight gain revealed no toxicologically relevant difference between the animals receiving 75, 250 or 750 mg/kg bw/d Citronellol and controls. A slight decrease of food consumption in the high-dose group at the beginning of treatment recovered soon and did not substantially influence average food consumption over the entire treatment period. Weighing of livers revealed significantly increased absolute and relative weights of this organ in the mid- and high-dose groups. However, concerning clinical pathology no treatment-related, adverse effects were observed up to a dose of the test item of 750 mg/kg bw/d. As there were no corresponding adverse changes in clinical chemistry parameters the liver weight increase is considered to be treatment-related but adaptive rather than adverse. All females of the high-dose group (750 mg/kg bw/d), nearly all (24 out of 25) females of the mid-dose group (250 mg/kg bw/d) and two females of the low-dose group (75 mg/kg bw/d) showed transient salivation after treatment. This salivation persisted in the respective animals for some minutes immediately after daily gavage dosing (i.e. up to 15 minutes). It is considered to be treatment-related, likely as a result of the bad taste of the test substance/vehicle preparation or due to local irritation of the upper digestive tract. It is not considered to be a sign of systemic toxicity.

No differences of toxicological relevance between the control and the treated groups (75, 250 or 750 mg/kg bw/d) were determined for any reproductive parameters, such as conception rate, mean number of corpora lutea, mean number of implantations, as well as pre- and postimplantation loss. Similarly, no influence of the test substance on sex distribution of the fetuses was noted at any dose.Mean fetal weights of the high-dose offspring were slightly (6%) but statistically significantly below the mean fetal control weights in this study.However, they were close to the mean of the historical control and well within the historical control range (3.1 – 4.0 in the 95% spread). In addition, there were no other findings recorded in this study at all which may hint to any potential influence of the test item on prenatal development.Thus, this isolated observation is not considered to be of toxicological concern.Overall, there was no evidence for toxicologically relevant adverse effects of the test substance on fetal morphology at any dose.

Under the conditions of this prenatal developmental toxicity study, the oral administration of Citronellol to pregnant Wistar rats from implantation to one day prior to the expected day of parturition (GD 6-19) caused no evidence of maternal toxicity. In conclusion, the no observed adverse effect level (NOAEL) for maternal toxicity is 750 mg/kg bw/d.

There were no toxicologically relevant adverse fetal findings evident. Thus, the no observed adverse effect level (NOAEL) for prenatal developmental toxicity is 750 mg/kg bw/d.

Justification for classification or non-classification

The current data do not fulfill the criteria for classification according to Regulation (EC) 1272/2008 or Regulation 67/548/EEC, thus a non-classification for Citronellol is warranted.