Vinyl laurate

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2008-06-18 to 2009-04-15

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD Guideline study under GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

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 (incl. QA statement)

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Vinyl laurate

EC Number:

218-414-7

EC Name:

Vinyl laurate

Cas Number:

2146-71-6

Molecular formula:

C14H26O2

IUPAC Name:

ethenyl dodecanoate

Details on test material:

- Name of test material (as cited in study report): Vinyl laurate
- Substance type: monomer
- Physical state: liquid
- Stability under test conditions: stable
- Storage condition of test material: At room temperature (20 ± 5 °C)

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories Ltd, Füllinsdorf/Switzerland
- Age at study initiation: 11 wks
- Weight at study initiation: Males: 287 to 329 g; Females: 180 to 215 g
- Fasting period before study: no
- Housing: macrolon type 3 cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 30 - 70
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12712


IN-LIFE DATES: From: 2008-06-18 To: 2008-08-18

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Justification for use and choice of vehicle (if other than water): solubility of test item
- Concentration in vehicle: depending on concentration used
- Amount of vehicle (if gavage): 5ml/kg bw
- Lot/batch no. (if required): 18787208

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

On the first treatment day samples from the control group as well as three samples (top, middle and bottom) of about 2 g of each concentration were taken prior to dosing for analysis of con-centration and homogeneity. Samples of about 2 g of each concentration were taken from the middle only to confirm stability (7 days). During the last week of the treatment, samples were taken from the middle to confirm concentration. The aliquots for analysis of dose formulations were frozen (-20 ± 5 °C) and delivered on dry ice to the responsible analyst and stored there at -20 ± 5 °C until analysis.
The samples were analyzed by GC coupled to an FI detector following an analytical procedure provided by the Sponsor and adapted at Harlan Laboratories. The test item was used as the analytical standard.

Duration of treatment / exposure:

Males: Minimum 4 weeks
Females: Approximately 7 weeks

Frequency of treatment:

once daily

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 50, 250 and 1000 mg/kg bw
Basis:
actual ingested

No. of animals per sex per dose:

10

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: The dose levels were selected based on a previous non-GLP dose range finding toxicity study in Han
Wistar Rats, RCC Study Number B85072, using dose levels of 100, 300, and 1000 mg/kg/day.
- Rationale for animal assignment (if not random): random

Positive control:

not applicable

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations checked in table were included.


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily cage-side clinical observations (once daily, during acclimatization and up to day of necropsy).
Additionally females were observed for signs of difficult or prolonged parturition, and behavioral abnormalities in nesting and nursing.


BODY WEIGHT: Yes
- Time schedule for examinations:Recorded daily from treatment start to day of necropsy.


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): not applicable

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): not applicable

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Other examinations:

none stated

Statistics:

The following statistical methods were used to analyze food consumption, body weights and
reproduction data:
• Means and standard deviations of various data were calculated.
• The Dunnett-test (many to one t-test) based on a pooled variance
estimate was applied if the variables could not be assumed to follow a normal
distribution for the comparison of the treated groups and the control groups for each sex.
• The Steel-test (many-one rank test) was applied instead of the
Dunnett-test when the data could not be assumed to follow a normal distribution.
• Fisher's exact-test was applied to the macroscopical finding

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Food efficiency:

no effects observed

Ophthalmological findings:

no effects observed

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Details on results:

Mean food consumption for males was slightly increased in group 4 during the pre-pairing pe-riod (+7.9% compared to the control group). However, this was not statistically significant and was not considered to be a toxic effect of the test item.
Mean body weight gain for males was slightly occasionally statistically significantly increased on single days in groups 3 and 4 during the pre-pairing period. This was considered to be a result of the slightly increased food consumption and not a test item-related effect.
During the pre-pairing and gestations periods, mean food consumption for females was in-creased in all groups receiving the test item but not statistically significantly and without dose-dependency. During the lactation period, mean food consumption was increased in group 4 (+12.1% compared to the control group). This effect was considered unlikely to be test item-related since no other toxic effects were noted in the dams.

Effect levels

Dose descriptor:

NOAEL

Effect level:

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

Sex:

male/female

Basis for effect level:

other: overall effects

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Substance did not adversly affect the animals under the conditions used.

Executive summary:

The effects of Vinyl laurate on the possible health hazards likely to arise from repeated exposure over a relatively limited period of time were assessed in a OECD 422 study. . In addition this combined repeated dose toxicity study with the reproduction/developmental toxicity screening test in the Han Wistar rat provides information on possible effects on male and female reproductive performance such as gonadal function, mating behavior, conception, development of the conceptus and parturition.

Vinyl laurate was administered to male rats for at least 28 days and to female rats for 14 days prior to pairing, through the pairing and gestation periods until the F1 generation reached day 4 post partum. The following dose levels were applied:

Group 1: 0 mg/kg body weight/day (control group), Group 2: 50 mg/kg body weight/day, Group 3: 250 mg/kg body weight/day, Group 4: 1000 mg/kg body weight/day. A standard dose volume of 5 mL/kg body weight with a daily adjustment to the actual body weight was used. Control animals were dosed with the vehicle alone (corn oil).

All parent animals survived until the scheduled necropsy. No clinical signs or observations were noted for any male or female in any groups during the duration of the study. No test item-related findings were noted in the Functional Observational Battery. Mean food consumption and body weights were note affected by treatment with the test item in the males and females during the study. No test item-related effects were noted from the clinical laboratory investigations. All female mated. No effects were noted in the reproduction and breeding data. No test item-related effects were noted in the organ weights. No test item-related macroscopical or histopathological findings were observed.

No test item-related findings at first litter check and during lactation were noted. Pup weights to day 4 post partumwere unaffected by treatment with the test item. No test item-related macroscopical findings were observed in the pups. .

The general NOEL (No Observed Effect Level) was considered to be 1000 mg/kg body weight/day.

The NOEL (No Observed Effect Level) for reproduction/developmental toxicity was also considered to be1000 mg/kg body weight/day.