2,2-bis[[(2-ethyl-1-oxohexyl)oxy]methyl]propane-1,3-diyl bis(2-ethylhexanoate)

Toxicity to reproduction

Administrative data

Endpoint:

screening for reproductive / developmental toxicity

Remarks:

based on test type (migrated information)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2004

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Individual data and analytical data are not available.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2,2-bis[[(2-ethyl-1-oxohexyl)oxy]methyl]propane-1,3-diyl bis(2-ethylhexanoate)

EC Number:

230-743-8

EC Name:

2,2-bis[[(2-ethyl-1-oxohexyl)oxy]methyl]propane-1,3-diyl bis(2-ethylhexanoate)

Cas Number:

7299-99-2

Molecular formula:

C37H68O8

IUPAC Name:

3-[(2-ethylhexanoyl)oxy]-2,2-bis({[(2-ethylhexanoyl)oxy]methyl})propyl 2-ethylhexanoate

Constituent 2

Reference substance name:

Pentaerythritol tetraiso-octylate

IUPAC Name:

Pentaerythritol tetraiso-octylate

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

See 7.5.1.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on exposure:

See 7.5.1.

Details on mating procedure:

1:1 up to 2 weeks until presence of semen in vaginal smear or presence of vaginal plug

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

See 7.5.1.

Duration of treatment / exposure:

2 weeks before mating, during mating and during gestation up to day 4 of lactation for females (42-54 days) and 2 weeks before mating, during mating till 42 days in total for males

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:0, 100, 300 and 1000 mg/kg bw/dBasis:actual ingested

No. of animals per sex per dose:

12

Control animals:

yes, concurrent vehicle

Examinations

Parental animals: Observations and examinations:

Specific fertility parameters: number of pairs copulated, pairing days until copulation, gestation length, number of corpora lutea, number of implantations.

Oestrous cyclicity (parental animals):

mean time of estrous cycle and incidence of animals with estrous cycle other than a 4-day cycle per dose was determined beginning at the start of dosing until confirmation of mating

Sperm parameters (parental animals):

None

Litter observations:

Number of (live) pups and sex ratio on day 0 and 4

Postmortem examinations (parental animals):

See 7.5.1.

Postmortem examinations (offspring):

None

Statistics:

See 7.5.1.

Reproductive indices:

Copulation index, fertility index, gestation index, imlantation index, delivery index.

Offspring viability indices:

Birth index, live birth index, viability index.

Results and discussion

Results: P0 (first parental generation)

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

no effects observed

Reproductive function: sperm measures:

not examined

Reproductive performance:

effects observed, treatment-related

Details on results (P0)

- Estrous cycle: no treatment-related effect on incidence and length of estrous cycle- Reproductive performance: All animals copulated, but one case in the 1000 mg/kg bw/d group failed to become pregnant. The ovaries of this case showed follicle cysts with an increase in follicles in the closed state. No significant differences were observed between the control group and any of the treatment groups in impregnation rate, number of days to copulation or number of estrous during this period. No significant differences were observed for corpus luteum count, implantation count or implantation rate between control and treated groups. In the absence of other findings in other animals the one non-pregnant female is considered to be an incidental case.

Effect levels (P0)

Dose descriptor:

NOAEL

Effect level:

>= 1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: absence of effects

Results: F1 generation

General toxicity (F1)

Clinical signs:

no effects observed

Mortality / viability:

no mortality observed

Body weight and weight changes:

no effects observed

Sexual maturation:

no effects observed

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

not examined

Histopathological findings:

not examined

Details on results (F1)

No effect on birth index, live birth index, viability index or sex ratio was observed. Morphological observations on day 0 of lactation showed a kinked tail in one pup at 1000 mg/kg bw/d. As no tail abnormalities were observed in any of the other animals, this was considered to be a spontaneous malformation. At necropsy no tail abnormalities were found (not clear if pup with kinked tail had died or not).

Effect levels (F1)

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

>= 1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: absence of effects

Overall reproductive toxicity

Reproductive effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

No reproductive effects were seen in a combined repeated dose/repro/developmental toxicity study in rats after oral gavage. The NOAEL was set at >=1000 mg/kg bw/d.

Executive summary:

No reproductive effects were seen in a combined repeated dose/repro/developmental toxicity study in rats after oral gavage. The NOAEL was set at >=1000 mg/kg bw/d.