Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Additional information

A multigenerational reproductive and developmental toxicity study has not been conducted with dihydromyrcenol. In a 90 -day repeated dose oral gavage study in rats with the analogue chemical, dimyrcetol, there were no effects noted in female rats on reproductive organs or oestrous cyclicity at the highest dose level tested (1000 mg/kg bwt/day). In male rats, spermatid counts in the testis at the highest dose were significantly reduced versus the control animals at the highest dose level. There were no similar reductions in spermatid counts in the cauda epididymis and no histopathological changes were associated with the reduced sperm counts. No further conclusions can be drawn from these findings.

In Annex IX of Regulation (EC) No 1907/2006, it is laid down that a 2-generation reproductive toxicity test shall be performed by the most appropriate route of administration and having regard to the likely route of human exposure. Given the low vapor pressure of the test material, exposure by the inhalation route is expected to be minimal. Dermal exposure in humans is anticipated, but in vitro dermal absorption testing with human skin of the analogue material, dimyrcetol, indicates only minimal potential dermal absorption (see Section 7.1.2). A 2 -generation reproductive toxicity test is proposed with administration by oral gavage. The dose levels proposed are 0, 250, 500 and 1000 mg/kg bwt/day. Inconclusive data from a 90 -day gavage study in rats with the analog chemical dimyrcetol indicates a possible effect on homogenization-resistant spermatid counts at a dose level of 1000 mg/kg bwt/day. Thus, in the proposed study, the total number of homogenization-resistant testicular and cauda epididymal spermatid counts shall be enumerated. Full histopathological analyses will also be performed on sexual organs from parental (P and F1) animals. Other analyses will be performed as appropriate. Update September 2015: in accordance with the amended REACH requirement, an OECD 416 is nolonger proposed. An EOGRTS (OECD 443) is now proposed. The justification for the study design is included as an attachment in a new endpoint study record.

Please refer to Section 13 of the file for read-across documentation and rationale for the use of analogue chemicals for dihydromyrcenol.


Short description of key information:
Reproductive organ and tissue effects and measurements of sperm count and mobility were determined in a 90-day oral gavage study in rats with the analogue chemical, dimyrcetol, following OECD Guideline 408.

Effects on developmental toxicity

Description of key information
Developmental toxicity was determined in rats following the ICH Harmonized Tripartite Guidelines (Stages C and D of the reproductive process) with the analogue chemical, dimyrcetol.
Effect on developmental toxicity: via oral route
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Additional information

There is no information available on the developmental toxicity of dihydromyrcenol. The developmental toxicity of the analogue chemical, dimyrcetol, has been determined in rats. Pregnant CD rats were treated with 0, 250, 500 or 1000 mg/kg bwt/day of the test material by gavage on gestation days 7 to 17 with sacrifice on day 21. Viability, clinical signs, body weights and feed consumption were measured for all animals. Fetuses were weighed and examined for sex, gross changes, and soft tissue or skeletal alterations. No clinical signs attributable to dimyrcetol administration were observed. Maternal body weights were minimally reduced at the highest dose level. Absolute and relative feed consumption were also reduced at this dose level. Maternal effects were associated with minimal reductions in fetal body weights, reversible variations in ossification and increases in supernumerary ribs with associated increases or decreases, respectively, in thoracic and lumbar vertebrae. The 1000 mg/kg bwt/day dose level was assigned as both the maternal and developmental NOAEL.

Please refer to Section 13 of the IUCLID file for read-across documentation and rationale for the use of analogue chemicals for dihydromyrcenol.

Justification for classification or non-classification

The analogue chemical, dimyrcetol, was not a selective developmental toxicant in CD rats at dose levels as high as 1000 mg/kg bwt/day. In a 90 -day oral gavage study in rats, dimyrcetol had no effects on the reproductive organs of female mice. In male rats, reduced spermatid counts were reported in the testes at the highest dose level tested, however, similar effects were not observed in the cauda epididymis nor were there any histopathological effects noted. Based on the evidence presented, dihydromyrcenol should not be rated as a reproductive hazard under the EU DSD classification system (EU Directive 647/548/EEC). Similarly, it would not be rated under the EU CLP classification system (EU Regulation 1272/2008), and UN-GHS.