Reaction mass of (3E)-1,1,1,2,2,3,4,5,6,6,7,7,7-tridecafluoro-5-methoxyhept-3-ene and (2E)-1,1,1,2,3,4,5,5,6,6,7,7,7-tridecafluoro-4-methoxyhept-2-ene and (3E)-1,1,1,2,2,4,5,5,6,6,7,7,7-tridecafluoro-3-methoxyhept-3-ene

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

This study was selected as the key study because the information provided for the hazard endpoint is sufficient for the purpose of classification and labeling and/or risk assessment. Although data provided have a report year after 2008, the study was performed to fulfill needs required by government regulators and/or for product stewardship purposes. DuPont’s stewardship principle states that “We will adhere to the highest standards for the safe operation of facilities and the protection of our environment, our employees, our customers and the people of the communities in which we do business”. The study was carried out in accordance with our internal Product Stewardship standard which is part of the American Chemical Council’s “Responsible Care Program”. This study was not performed to fulfill an information requirement under REACH, but since the test data were already available they were provided as part of the REACH submission.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Deviations:

no

Remarks:

The study was conducted according to the guideline in effect at the time of study conduct.

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.31 (Prenatal Developmental Toxicity Study)

Deviations:

no

Remarks:

The study was conducted according to the guideline in effect at the time of study conduct.

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.3700 (Prenatal Developmental Toxicity Study)

Deviations:

no

Remarks:

The study was conducted according to the guideline in effect at the time of study conduct.

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: MAFF Japan The Guidelines Related to the Study Reports for the Registration Application of Pesticides, 12 Nousan Number 8147

Deviations:

no

Remarks:

The study was conducted according to the guideline in effect at the time of study conduct.

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

(2E)-1,1,1,2,3,4,5,5,6,6,7,7,7-tridecafluoro-4-methoxyhept-2-ene; (3E)-1,1,1,2,2,3,4,5,6,6,7,7,7-tridecafluoro-5-methoxyhept-3-ene; (3E)-1,1,1,2,2,4,5,5,6,6,7,7,7-tridecafluoro-3-methoxyhept-3-ene

EC Number:

700-755-2

Molecular formula:

C8H3F13O

IUPAC Name:

(2E)-1,1,1,2,3,4,5,5,6,6,7,7,7-tridecafluoro-4-methoxyhept-2-ene; (3E)-1,1,1,2,2,3,4,5,6,6,7,7,7-tridecafluoro-5-methoxyhept-3-ene; (3E)-1,1,1,2,2,4,5,5,6,6,7,7,7-tridecafluoro-3-methoxyhept-3-ene

Details on test material:

- Purity: >99%

Test animals

Species:

rat

Strain:

other: Crl:CD(SD)

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: approximately 69-72 days
- Weight at study initiation: 228 g to 285 g
- Housing: Individually in solid bottom cagging with bedding containing Envirodry(TM) as enrichment
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 3 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-26°C
- Humidity (%): 30-70%
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: The test substance was dosed undiluted. Animals were dosed daily at approximately the same time by gavage. The amount of test substance each rat received was based on the most recently collected body weight and the density of the test substance. Control rats were dosed with deionized water at the same volume as the high dose group.

Analytical verification of doses or concentrations:

no

Details on mating procedure:

- Impregnation procedure: purchased timed pregnant

Duration of treatment / exposure:

Gestation Days 6-20

Frequency of treatment:

Daily

Duration of test:

21 days

No. of animals per sex per dose:

22 females per dose

Control animals:

yes

Details on study design:

- Dose selection rationale: Doses were selected based on results from previous toxicity studies and the limitations of dose volume when the test substance was dosed neat.

Examinations

Maternal examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: once on day 4G; twice daily on days 6-20G (during weighing and at least 2 hours post-dosing); once on day 21G

BODY WEIGHT: Yes
- Time schedule for examinations: daily on days 4 and 6-21G

FOOD CONSUMPTION: Yes
- Food consumption for each animal determined: days 4, 6, 8, 10, 12, 14, 16, 18, 20, and 21G

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 21
- Organs examined: a gross external and a visceral examination were performed.

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes

Fetal examinations:

- External examinations: Yes: all per litter
- Soft tissue examinations: Yes: half per litter
- Skeletal examinations: Yes: all per litter (skulls of half per litter)
- Head examinations: Yes: half per litter

Statistics:

See Table below.

For litter parameters, the proportion of affected fetuses per litter or the litter mean were used as the experimental unit for statistical evaluation. Significance was judged at p < 0.05.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:no effects

Effect levels (maternal animals)

1

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (actual dose received)

Based on:

test mat.

Basis for effect level:

other: maternal toxicity

2

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (actual dose received)

Based on:

test mat.

Basis for effect level:

other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
There was a statistically significant increase in fetal sex ratio at 500 and 1000 mg/kg/day. These instances of statistical significance are attributed to an atypically low value for the concurrent control group. These changes are not considered test substance-related because fetal sex is determined at the time of conception on GD 0 and dosing was not initiated until GD 6. Fetal sex ratio is useful as an endpoint on a developmental toxicity study that employs the current design only to the extent that one can infer whether or not there is a gender-specific difference in in utero survival. In this case, there were no effects on in utero survival. Therefore, the changes in the means are considered to have occurred by chance. The mean values for all groups in the current study fall within typical published ranges generally seen in control populations.

Effect levels (fetuses)

Dose descriptor:

LOEC

Effect level:

500 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

not specified

Basis for effect level:

changes in sex ratio

Remarks on result:

not determinable due to absence of adverse toxic effects

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

NOAEL (maternal) = 1000 mg/kg (highest dose tested)
NOAEL (developmental) = 1000 mg/kg (highest dose tested)

This study and the conclusions which are drawn from it fulfill the quality criteria (validity, reliability, repeatability).

Executive summary:

The objective of the study was to evaluate the potential maternal and developmental toxicity of the test substance in rats. The test substance was administered via once-daily oral gavage as neat material. Groups of 22 time-mated Crl:CD(SD) rats were administered the test substance at dose levels of 0, 250, 500, or 1000 mg/kg/day. Dosing was initiated on gestation day (GD) 6 and continued through GD 20. During the in-life portion of the study, maternal body weights and food consumption as well as clinical observations data were collected. On GD 21, dams were euthanized and underwent a gross external and internal examination. The gravid uteri were removed, weighed, and dissected. Uterine contents were described and fetuses were counted, weighed, sexed, and examined for external, visceral, head, and skeletal alterations.

There was no evidence of test substance-related maternal or developmental toxicity at any dose level tested and the no-observed-adverse-effect level (NOAEL) was 1000 mg/kg/day for both maternal and developmental toxicity.