Hydrocarbons, C4, 1,3-butadiene-free, polymd., tetraisobutylene fraction

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:

1994-03-17 to 1994-07-11

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study is classified as reliable without restrictions because it was conducted according to OECD 422 guidelines and was GLP complaint.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

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)

Deviations:

no

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Tetradec-1-ene

EC Number:

214-306-9

EC Name:

Tetradec-1-ene

Cas Number:

1120-36-1

Molecular formula:

C14H28

IUPAC Name:

tetradec-1-ene

Details on test material:

- Name of test material (as cited in study report): Blended from equal amounts of Neodene 14 alpha olefin, alpha olefin C14 1-tetradecene, and 1-tetradecene Gulftene 14
- Substance type: C14 alpha olefin
- Physical state: Clear colourless liquid
- Analytical purity: 99.0% to 99.98%
- Lot/batch No.: Neodene 14 alpha olefin 20202-45-1050, alpha olefin C14 1-tetradecene 300-954, and 1-tetradecene Gulftene 14 CBN0048
- Expiration date of the lot/batch: Only provided for Neodene 14 alpha olefin, 1994-12
- Storage condition of test material: Room temperature under nitrogen

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Inc., Portage, Michigan
- Age at study initiation: (P) Males: 6 weeks; Females: 8 weeks; F1 offspring not treated
- Weight at study initiation: (P) Males: 159 to 220 grams; Females: 184 to 242 grams
- Fasting period before study: No
- Housing: Individually except during cohabitation; males were also housed 2 to 3 to a cage during the first 4 days of acclimation
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 11 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 to 25°C
- Humidity (%): 21 to 79%
- Air changes (per hr): 10 to 12
- Photoperiod (hrs dark / hrs light): 12 hours dark/12 hours light

IN-LIFE DATES: From:1994-03-17 To:1994-05-03

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: After stirring the blended test material for 15 minutes, a specified amount of test material was added to a flask with half of the corn oil. The flasks were capped and inverted several times, then the remaining corn oil was added and the procedure repeated. The solution was then stirred for 15 minutes. Preparations were kept for a maximum of 28 days.

VEHICLE
- Concentration in vehicle: 0, 20, 100, or 200 mg/mL
- Amount of vehicle (if gavage): 5 mL/kg
- Lot/batch no. (if required): APR0695A, OCT0494A, and DEC2194A

Details on mating procedure:

- M/F ratio per cage: 1 to 1
- Length of cohabitation: 15 day
- Proof of pregnancy: Vaginal plug or sperm in vaginal smear referred to as day 0 of pregnancy; after 10 days of unsuccessful pairing replacement of first male by another male with proven fertility.
- Further matings after two unsuccessful attempts: No
- After successful mating each pregnant female was caged (how): Individually in nesting box

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Top, middle, and bottom samples of a 20 and 200 mg/mL dose formulation were tested to determine homogeneity. All samples were within 6% of the nominal concentration indicating that the dose formulations were homogeneous. Stability was tested on the 20 and 200 mg/mL dose formulation stored in the refrigerator and sampled at 3, 8, 15, and 29 days. The dose formulations were found to be stable under these conditions with all samples within 7% of the nominal value. All dose formulations were tested during weeks 1, 3, and 7 and were all found to be within 4% of the nominal concentration.

Duration of treatment / exposure:

Males: 28 days prior to mating and until the day prior to euthanasia (43 to 47 days)
Females (breeding): 14 days prior to mating, during mating, gestation, and lactation, and until the day prior to euthanasia (42 to 51 days)

Frequency of treatment:

Daily

Details on study schedule:

There were no F1 parental animals.

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 100, 500, 1000 mg/kg/day
Basis:
actual ingested

No. of animals per sex per dose:

12 animals per sex per dose

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: Doses were selected bases on a range-finding study.

Positive control:

None

Examinations

Parental animals: Observations and examinations:

CAGE SIDE OBSERVATIONS: No

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Once daily except mortality which was checked twice a day.

BODY WEIGHT: Yes
- Time schedule for examinations: Weekly and in pregnant rats on day 0, 7, 14, and 20 of gestation and day 1 and 4 of lactation

FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: No

CLINICAL CHEMISTRY: No

URINALYSIS: No

Oestrous cyclicity (parental animals):

Not examined

Sperm parameters (parental animals):

Parameters examined in P male parental generations: Testis weight and epididymis weight

Litter observations:

STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: No


PARAMETERS EXAMINED
The following parameters were examined in F1: number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, weight gain, physical or behavioural abnormalities


GROSS EXAMINATION OF DEAD PUPS:
yes, for external and internal abnormalities; possible cause of death was not determined for pups born or found dead.

Postmortem examinations (parental animals):

SACRIFICE
- Male animals: All surviving animals on day 47.
- Maternal animals: All surviving animals on lactation day 4.

GROSS NECROPSY
- Gross necropsy consisted of external and internal examinations including the cervical, thoracic, and abdominal viscera.

HISTOPATHOLOGY / ORGAN WEIGHTS: Histopathology and organ weights were only performed in males and nonbreed females. Organs examined in 5 randomly selected males and females are marked in Table 2. Organs weighed are marked twice. Organs were collected from breed females, but were stated to be collected for possible future examination.

Postmortem examinations (offspring):

SACRIFICE
- The F1 offspring were sacrificed at 4 days of age; these animals were subjected to postmortem examinations (macroscopic) and as follows:

GROSS NECROPSY
- Gross necropsy consisted of external and internal examinations including the cervical, thoracic, and abdominal viscera.

Statistics:

A one-way ANOVA followed by a Dunnett's or modified Dunnett's test was used for continuous data. Chi-square test was used for count data. Two-tailed analyses were used with p<0.05.

Reproductive indices:

Fertility, gestation, parturition, and lactation

Offspring viability indices:

Live and dead pups, number of litters with live offspring, mean live litter size, male to female ratio, and the number of survivors

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

effects observed, treatment-related

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Other effects:

not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

not examined

Reproductive function: sperm measures:

not examined

Reproductive performance:

no effects observed

Details on results (P0)

CLINICAL SIGNS AND MORTALITY (PARENTAL ANIMALS): Breeding females administered 500 and 1000 mg/kg/day had urine stains and salivation (post-dosing).


BODY WEIGHT AND FOOD CONSUMPTION (PARENTAL ANIMALS): Body weight was not affected by treatment. There were sporadic changes in food consumption, but since the results are not related to changes in body weight it is not considered related to treatment.


REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS): There were no changes in reproductive performance.

ORGAN WEIGHTS (PARENTAL ANIMALS): There were no differences in reproductive organ weights.

GROSS PATHOLOGY (PARENTAL ANIMALS): Gross pathology did not indicate any differences in reproduction or the reproductive organs.

HISTOPATHOLOGY (PARENTAL ANIMALS): Histopathology in the males did not indicate any differences in the reproductive organs. Histopathology in nonbreed females did not indicate any affect on reproductive organs. Histopathology was not conducted on the breeding females.

OTHER FINDINGS (PARENTAL ANIMALS)

Effect levels (P0)

Dose descriptor:

NOEL

Effect level:

1 000 mg/kg bw/day

Sex:

male/female

Basis for effect level:

other: Overall effects

Results: F1 generation

General toxicity (F1)

Clinical signs:

not examined

Mortality / viability:

no mortality observed

Body weight and weight changes:

no effects observed

Sexual maturation:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

no effects observed

Histopathological findings:

not examined

Details on results (F1)

VIABILITY (OFFSPRING): There were no effects on viability.


BODY WEIGHT (OFFSPRING): There were no effects on body weight at birth or lactation day 4.


GROSS PATHOLOGY (OFFSPRING): There were no treatment-related effects on gross pathology.

Effect levels (F1)

Dose descriptor:

NOEL

Generation:

F1

Effect level:

1 000 mg/kg bw/day

Sex:

male/female

Basis for effect level:

other: Live birth index, pup weight, sex ratio, survival index, viability index, no gross abnormalities

Overall reproductive toxicity

Reproductive effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

A reproductive/developmental NOEL of 1000 mg/kg/day was established for both males and females.

Executive summary:

In this screening for reproductive/developmental toxicity study, 1 -tetradecene was administered via gavage to twelve Sprague-Dawley Crl:CDBR VAF/Plus rats/sex/dose at doses of 0, 100, 500, or 1000 mg/kg/day (5 mL/kg of 0, 20, 100, or 200 mg/mL solution in corn oil). The test material was composed of equal amounts of Neodene 14 alpha olefin, alpha olefin C14 1 -tetradecene, and 1 -tetradecene Gulftene 14, which were obtained from different sources. Males were treated for 43 to 47 days beginning 28 days prior to mating and females were treated for 42 to 51 days beginning 14 days prior to mating through lactation day 4.

No reproductive or developmental effects were observed. There were clinical signs noted in 500 and 1000 mg/kg/day females, but they were unrelated to reproduction. There was no LOEL for this study. The NOEL for reproductive and developmental toxicity was 1000 mg/kg/day.