Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Additional information

No key study to address effects on fertility is available for tetrahydrogeraniol. According to the OECD SIDS for members of the Oxo Alcohols C9 to C13 Category as structurally analogs to tetrahydrogeraniol, the following is stated: 

“Developmental toxicity studies conducted by the oral route on isononyl alcohols, isodecanol, 2-propylheptanol and isotridecanol demonstrated that these materials do not affect reproductive parameters. Although a slight increase in resorptions was observed in several of the studies, this only occurred in the highest dose group(s) and in the presence of overt maternal toxicity. NOAELs for developmental toxicity ranged from 144-1440 mg/kg bw/day. As supporting information, testing of 1-dodecanol in a combined repeated dose developmental /reproductive study showed no effects to parents or offspring at levels up to 2000 mg/kg bw/day. Furthermore, inhalation exposure to vapors, at levels of 150 and 100 mg/m3 of respectively 1-nonanol and 1-decanol, did not induce any statistically significant changes in reproductive parameters. In the 14-day repeat dose studies of isononanol, isodecanol and isotridecanol, no changes in testicular weight were observed. These data support the conclusion that members of the Oxo Alcohols C9 to C13 category are not selective reproductive toxicants.” (SIDS INITIAL ASSESSMENT PROFILE, attached to 7.12).

Overall, structurally analogs to tetrahydrogeraniol do not give indications for adverse effects on reproductive organs or tissues, therefore no rationale for a reproductive toxicity study (e.g. a two-generation study) with tetrahydrogeraniol is given based on the current data available. 

Effects on developmental toxicity

Additional information

Developmental toxicity was evaluated in a study performed according to OECD Guideline 414 (BASF SE, 2016). The test substance Tetrahydrogeraniol was administered as a solution in corn oil to 25 "time-mated" (mated by breeder) female Wistar rats/group by stomach tube at doses of 50, 150 and 450 mg/kg bw on day 6 through day 19 post coitum (p.c.). The high dose was selected based on signs of toxicity noted at dose levels of 300 and 1000 mg/kg bw/d in a previously conducted maternal toxicity range-finding study which preceded this definitive prenatal developmental toxicity study. In the maternal toxicity rangefinding study, 7 pregnant Wistar rats per group were administered the test substance by oral gavage from gestational day (GD) 6 through GD 19. At 1000 mg/kg bw/d 4 dams died or were sacrificed moribund on GD 7 and the remaining 3 dams were sacrificed in serious condition two days later, showing signs of salivation, piloerection, head shaking, unsteady gait, labored respiration, abdominal position and hypothermia. Dams treated with 300 mg/kg bw/d showed salivation (all) and one case of piloerection and semiclosed eyelids. For these reasons, the dose level of 1000 mg/kg bw/d was considered to be potentially lethal to the dams in the OECD 414 study.

On day 20 p.c., all females were sacrificed and assessed by gross pathology including the uterus and the placentae where corpora lutea were counted and number and distribution of implantation sites (differentiated as resorptions, live and dead fetuses) were determined. The fetuses were removed from the uterus, sexed, weighed, and further investigated for any external findings. Thereafter, one half of the fetuses of each litter were examined for soft tissue findings and the remaining fetuses for skeletal findings.

Under the conditions of this prenatal developmental toxicity study, the oral administration of Tetrahydrogeraniol to pregnant Wistar rats from implantation to one day prior to the expected day of parturition (GD 6-19) at doses as high as 450 mg/kg bw/d caused neither evidence of maternal nor developmental toxicity.

In conclusion, the no observed adverse effect level (NOAEL) for maternal and prenatal developmental toxicity is 450 mg/kg bw/d.

Justification for classification or non-classification

The present data on reproductive toxicity do not fulfill the criteria laid down in 67/548/EEC and regulation (EU) 1272/2008, and therefore, a non-classification is warranted.