Cyclooctanone

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Hall et al. (1974) reported results on female and male mouse fertility screenings after exposure to cyclooctanone. After 28 days of i.p. dosing of 50 mg/kg/ day thenumber of pregnancies, viable fetuses, dead in uterine and resorptions were recorded. The percentage of pregnancies was 88%, viable fetuses per litter 109% and resorption per litter 170% compared to vehicle treated control. Male mice were dosed with 10 mg/kg/day according to the methode of Coppola (1969). No effects on male fertility were observed, as male mice copulated successfully with females and mating led to viable offspring.

Link to relevant study records

Reference

Endpoint:

fertility, other

Type of information:

experimental study

Remarks:

publication

Adequacy of study:

other information

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

For female mouse fertility screening test, female CF1 mice were weighted and administered 50 mg/kg of the test material daily ip for a total of 28 days. On the tenth day of dosing, the females were exposed to males (two females/male) for the remaining experiment. The males were rotated every fifth day. After 28 days of dosing, females were sacrificed. The number of pregnancies, viable fetuses, dead in uterine and resorptions were recorded.
For male fertility screening test, male CF1 mice were dosed with 10 mg/kg/day according to the methode of Coppola (Coppola, J.A. (1969) An extragonadal antifertility agent. Life Sciences 8, 43-48).

GLP compliance:

not specified

Specific details on test material used for the study:

The test material was suspended in 1% carboxymethylcellulose (CMC) and homogenised.

Species:

mouse

Strain:

CF-1

Sex:

male/female

Route of administration:

intraperitoneal

Vehicle:

CMC (carboxymethyl cellulose)

Details on exposure:

50 mg/kg/day test material suspended in 1% carboxymethylcellulose (CMC) administered in 0.2 cc ip.
Doses were adjusted for weight gains during the experiment.

No. of animals per sex per dose:

8 females for fertility screening

Control animals:

yes, concurrent vehicle

Mortality:

no mortality observed

Body weight and weight changes:

not specified

Reproductive performance:

no effects observed

Description (incidence and severity):

female fertility: (percentage of control)
Pregnancies: 88%
Viable fetuses per litter: 109%
Reabsorption per litter: 170%

male fertility:
no effects on male fertility (copulated successfully with fertile females resulted in viable offspring)

A change greater than 25% is considered to be significant concerning female fertility. The average number of fetuses and reabsorption sites for the control including uterine death for CFI mice was 12±3 and 0.48±0.12 per litter, respectively. These values were set equivalent to 100%.

Remarks on result:

not determinable due to absence of adverse toxic effects

Conclusions:

Based on fertility screening after intraperitoneal administration for a period of 28 days the NOAEL for cyclooctanone was set at ≥ 50 mg/kg/day in female CF1 mice. Due to no effects in male mouse fertility screen, the NOAEL for cyclooctanone was set at ≥ 10 mg/kg/day in male CF1 mice. Based on the available information, no classification for adverse effects on sexual function and fertility according to CLP Regulation (EC) No. 1272/2008 is required.

Effect on fertility: via oral route

Endpoint conclusion:

no study available

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

i.p. administration of cyclooctanone to female mice for 28 days resulted in NOAEL (reproduction): ≥50 mg/kg/day

Effects on developmental toxicity

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Toxicity to reproduction: other studies

Description of key information

Harvey and Cowley (1984) investigated the effects of cyclooctanone exposure via inhalation for the first three weeks of life to female mice. The exposure to 7.3 x 10^-5 M cyclooctanone led to no differences in age of sexual maturation and no adverse effects on behavior. Cellular changes in olfactory bulbs were detected but considered to be non-adverse and of no relevance for developmental toxicity.

Link to relevant study records

Reference

Endpoint:

toxicity to reproduction: other studies

Remarks:

developmental toxicity

Type of information:

experimental study

Remarks:

publication

Adequacy of study:

other information

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

Female mice were reared and observated from day 1 of life for three weeks. They were continously exposed to the odors of either cyclooctanone, adult male mouse urine or distilled water as control. Body weight, vaginal opening and first oestrus, olfactory preference, behavior and histological analysis of olfactory bulbs was recorded.

GLP compliance:

no

Type of method:

in vivo

Specific details on test material used for the study:

cyclooctanone crystals (Koch-Light Laboratories, Bucks)

Species:

mouse

Strain:

other: T.O. mice

Sex:

female

Route of administration:

inhalation

Vehicle:

unchanged (no vehicle)

Details on exposure:

odorants were placed in petri dishes below the wire mesh floor of the living area of the observation incubators and in the path of the airflow which was fed in from outside the building by a vacuum/pressure pump with an output of approximately 1 L/min. Odorants were placed in the incubators daily.

Duration of treatment / exposure:

from day 1 of life for three weeks

Frequency of treatment:

continously

Duration of test:

up to 8 months

Dose / conc.:

0.25 other: g

Remarks:

giving an average molar concentration of 7.3 x10^-5 M

No. of animals per sex per dose:

23 per dose

Control animals:

yes, sham-exposed

Body weigth: stat. sign. Increased on day 16, other days no differences

Vaginal opening: at day 26.45 (control at day 27.37)
First oestrus: at day 30.77 (control at day 30.89)

Behavior: No treatment effect on grooming; altered sniffing pattern over days but not generally increased

Histology of olfactory bulb: significantly wider olfactory bulbs, significantly greater overall number of altered mitral cells

Conclusions:

Exposure to cyclooctanone via inhalation for the first three weeks of life leads to no difference in age of sexual maturation of female mice. Exposure during neonatal period of female mice showed cellular changes in olfactory bulbs but effects were not considered adverse. Behavior was not adversely affected by exposure to cyclooctenone.

Justification for classification or non-classification

Data on sexual function and fertility after exposure to cyclooctanone was published by Hall et al. (1974) in non-OECD screening tests. Number of pregnancies, viable fetuses and resorption per litter showed no clear evidence of reproductive toxicity on female mice. In addition, no effects on male fertility were evident.

Since no OECD study on developmental toxicity is available, the information on neonatal exposure of female mice reported by Harvey and Cowley (1984) could be considered for this endpoint. The exposure to cyclooctanone via inhalation during neonatal period of female mice showed no adverse effects no sexual maturation, behavior and histopathology of olfactory bulbs.

Based on the available infomation with limited reliability, the test item cyclooctanone requires no classification for reproductive toxicity according to CLP Regulation (EC) No. 1272/2008.