Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Additional information

In Column 2 of REACH Annex VIII it is stated that “a screening study for reproductive/developmental toxicity does not need to be conducted if a pre-natal developmental toxicity study or a two-generation reproductive toxicity study is available.” Since data on developmental toxicity are available to fill in the data-gap for delta-damascone, the reproductive toxicity study does not need to be conducted. Furthermore, Column 1 of REACH Annex IX states that “a two-generation reproductive toxicity study, one species, male and female, most appropriate route of administration having regard to the likely route of human exposure” needs to be conducted “if the 28-day or 90-day study indicates adverse effects on reproductive organs or tissues”. Since the 90-day study with an appropriate read-across candidate of delta-damascone, alpha-iso-methylionone, does not indicate any adverse effect on reproductive organs or tissues, the conductance of a two-generation reproductive toxicity study is also not necessary.


Short description of key information:
No studies on effects on fertility with delta-damascone were available. A 90-day study with an appropriate read-across candidate of delta-damascone, alpha-iso-methylionone (EC name: 3-methyl-4-(2,6,6-trimethyl-2-cyclohexen-1-yl)-3-buten-2-one) was available, which did not indicate any adverse effect on reproductive organs or tissues. Furthermore, the developmental toxicity study with alpha-iso-methylionone showed no effects on development at the highest dose tested.

Effects on developmental toxicity

Description of key information
A developmental toxicity study with an appropriate read-across candidate of delta-damascone ((alpha-iso-methylionone (EC name: 3-methyl-4-(2,6,6-trimethyl-2-cyclohexen-1-yl)-3-buten-2-one))) was available which showed no adverse effects on development at the highest dose tested.
Effect on developmental toxicity: via oral route
Dose descriptor:
NOAEL
30 mg/kg bw/day
Additional information

Developmental toxicity

The appropriate read-across candidate of delta-damascone, alpha-iso-methylionone (EC name:3-methyl-4-(2,6,6-trimethyl-2-cyclohexen-1-yl)-3-buten-2-one) was tested in an oral (gavage) developmental toxicity study with rats (Charles River, 2005)

One hundred pregnant Crl: CD®(SD) IGS BR VAF/Plus® rats were randomly assigned to four dosage groups, 25 rats per group. The test article, alpha-iso-methylionone, and/or the vehicle, corn oil, was administered to the rats orally (gavage) once daily on days 7 through 17 of presumed gestation (gestation days (GD) 7 through 17) at dosages of 0, 3, 10 and 30 mg/kg bw/day. The dosage volume was 10 mL/kg, based on individual body weights recorded daily before administration.

Viabilities, clinical observations, body weights and feed consumption values were recorded. All rats were sacrificed on GD 21, Caesarean-sectioned and examined for the number and distribution of corpora lutea, implantation sites and uterine contents. A gross necropsy of the thoracic, abdominal and pelvic viscera was performed. Fetuses were weighed and examined for gross external, visceral and skeletal alterations and sex.

All female rats survived to scheduled sacrifice. All clinical and necropsy observations were considered to be unrelated to alpha-iso-methylionone. Maternal body weights, body weight gains and absolute and relative feed consumption values were unaffected at dosages of alpha-iso-methylionone as high as 30 mg/kg bw/day. Pregnancy occurred in 21 to 25 rats in each dosage group. Caesarean-sectioning and litter parameters were not affected by dosages of the test article as high as 30 mg/kg bw/day. No fetal alterations occurred that were considered associated with alpha-iso-methylionone.

On the basis of these data, the maternal and developmental NOAEL of alpha-iso-methylionone is greater than 30 mg/kg bw/day. No effects were observed at the highest dosage tested. There were no adverse effects on embryo-fetal development. Based on these data on the read-across candidate alpha-iso-methylionone, delta-damascone should not be identified as developmental toxicant.

Justification for classification or non-classification

In accordance with Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, classification is not necessary for developmental toxicity.

No fertility toxicity studies are available for delta-damascone. Since data on developmental toxicity are available to fill in the data-gap for delta-damascone, the reproductive toxicity study does not need to be conducted. Furthermore, Column 2 of REACH Annex IX states that “a two-generation reproductive toxicity study, one species, male and female, most appropriate route of administration having regard to the likely route of human exposure” needs to be conducted “if the 28-day or 90-day study indicates adverse effects on reproductive organs or tissues”. Since the 90-day study with an appropriate read-across candidate of delta-damascone (alpha-iso-methylionone) does not indicate any adverse effect on reproductive organs or tissues, the conductance of a two-generation reproductive toxicity study is also not necessary. Based on this, classification is not necessary for effects on fertility in accordance to Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.