Cyclododeca-1,5,9-triene

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Dose descriptor:

NOAEL

300 mg/kg bw/day

Additional information

Combined repeated dose toxicity study with the reproduction developmental toxicity screening test (OECD 422): Oral route

Following the 4-week premating period, each female was paired with a male of the same dosage group during a 1-2 week mating period. Measurements of body weight, food consumption, food efficiency, and clinical signs of toxicity in females were conducted weekly during gestation and on lactation days 0 and 4. At the end of an approximately 3-week post- mating period, surviving males

and presumed nonpregnant females were sacrificed, and on lactation day 4, lactating females and offspring were sacrificed. Ten organs were weighed, and 40 tissues were preserved for microscopic examination. The testes, epididymides, ovaries, and gross lesions from all high-dose and control group rats were examined microscopically. All other preserved tissues from 5 male and 5 female rats, randomly selected from the high-dose and control groups were examined microscopically. Livers from 5 randomly

selected female rats in the 30 and 100 mg/kg/day groups that delivered at least 1 live offspring were also examined microscopically. Offspring were weighed and evaluated for clinical abnormalities. Reproductive parameters recorded or calculated included gestation length, mating index, gestation index, fecundity index, implantation site numbers, implantation efficiency, sex ratio, pups born alive, and

viability index.

There were no test substance-related effects on reproductive parameters, which included gestation length, mating index, gestation index, fecundity index, implantation site numbers, implantation efficiency, sex ratio, pups born alive, and viability index. There any no changes in neurobehavioral parameters, or motor activity.

There were no test substance-related effects on clinical observations, number of pups born, number of pups born alive, or number of pups surviving through lactation day 4. Body weights of pups in the 300 mg/kg/day group were significantly decreased on lactation days 0 and 4.

Based the resuls of this study, the NOAEL for maternal toxicity was 30 mg/kg bw/d based on decreased on bodyweight gain, the NOAEL for reproductive performance (fertility) was 300 mg/kg bw/d because no effect was observed in this study; and the NOAEL for developmental study was 100 mg/kg bw/d because pup bodyweightd were significantly decreased on lactation days 0 and 4 at 300 mg/kg bw/d.

Short description of key information:
By oral route, a reliable OECD 422 study is available in rats with 1,5,9-cyclododecatriene. Based the resuls of this study, the NOAEL for maternal toxicity was 30 mg/kg bw/d based on decreased on bodyweight gain, the NOAEL for reproductive performance (fertility) was 300 mg/kg bw/d because no effect was observed in this study; and the NOAEL for developmental study was 100 mg/kg bw/d because pup bodyweightd were significantly decreased on lactation days 0 and 4 at 300 mg/kg bw/d.

Effects on developmental toxicity

Description of key information

A developmental study by inhalation is available on rats. In this study, the NOAEL for maternal toxicity was 10 ppm (67.5 mg/m3), based on decrease of bodyweight and food consumption at 25 ppm. Developmental toxicity was observed at 67 ppm, the NOAEL for developmental toxicity was 25 ppm (169 mg/m3). Therefore, the results of this study indicate that 1,5,9-cyclododecatriene is not likely to be uniquely toxic to the rat conceptus.

Effect on developmental toxicity: via oral route

Dose descriptor:

NOAEL

100 mg/kg bw/day

Effect on developmental toxicity: via inhalation route

Dose descriptor:

NOAEC

169 mg/m³

Additional information

Developmental study on rats by inhalation

Female rats were exposed to 1,5,9 -cyclododecatriene aerosolat 10, 25 and 67 ppm (corresponding to 67.5, 169 and 452 mg/m3 respectively) from gestation day 6 to day 20. Observations for morbidity and mortality were made daily. Body weights, food consumption, and individual clinical signs were recorded. Females were euthanized on GD 21 and the organs of the thoracic and abdominal cavities were examined for gross pathologic changes. The intact and empty uterine weights were recorded to calculate maternal body weight adjusted to exclude the products of conception. The corpora lutea count for each ovary of dams with viable

fetuses was recorded. For each female with visible implants, the type (live and dead fetuses, and resorptions) and their relative positions were recorded. The uterus of each apparently “nonpregnant” rat was stained to detect very early resorptions. The body weight, sex, and external alterations for each fetus were recorded. For each litter, the first live fetus and every other live fetus thereafter were examined for visceral alterations. The heads of decapitated fetuses were fixed, examined, and alterations were recorded. The remaining fetuses were euthanized. Skeletal alterations were recorded for all live fetuses.

Maternal toxicity was observed in this study, clinical observations, a decreased of bodyweight gain and food consumption were observed at 25 and 67 ppm.

There were no mortalities or early deliveries observed at any dose level. There were no compound-related effects on mean number of

corpora lutea, implantations, resorptions, live fetuses, or fetal sex ratio at any exposure level. There was no evidence of compound-related embryolethality at any exposure level tested.

No evidence of developmental toxicity was observed at 10 and 25 ppm. The only evidence of developmental toxicity was a significant reduction in mean fetal weight, and a concomitant increase in the incidence of delayed skeletal ossification at 67 ppm.

The NOAEL for maternal toxicity was 10 ppm (67.5 mg/m3), based on decrease of bodyweight and food consumption at 25 ppm. Developmental toxicity was observed at 67 ppm, the NOAEL for developmental toxicity was 25 ppm (169 mg/m3). Therefore, the results of this study indicate that 1,5,9-cyclododecatriene is not likely to be uniquely toxic to the rat conceptus.

Justification for classification or non-classification

Proposed self-classification

- Regulation (EC) No 1272/2008

Not classified

- Directive 67/548/EEC

Not classified