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EC number: 639-566-4 | CAS number: 165184-98-5
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
![](https://echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
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:
- 2009-2010
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Study conducted under GLP and according to guideline. It is a dose-range finding study and therefore limited investigations were conducted but sufficient for a screening of reproductive and developmental effects.
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 010
- Report date:
- 2010
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
- Deviations:
- yes
- Remarks:
- 8 animals/sex/group while the guidelines indicate almost 10 animals/sex/group
- Principles of method if other than guideline:
- Not applicable
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Details on test material:
- - Name of test material (as cited in study report): Hexylcinnamic aldehyde; octanal, 2-(phenylmethylene)-
- Physical state: Yellow liquid
- Analytical purity:98.6%
- Lot/batch No.:2814692
- Storage condition of test material:Room temperature, protected from light
- Other: Source: International Flavors and Fragrances, Inc., Union Beach, NJ
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Crj: CD(SD)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories Inc.
- Age at study initiation: (P) Males: 85 days; Females: 79 days
- Weight at study initiation: (P) Males: 316-342 g; Females: 201-230 g
- Fasting period before study:no data
- Housing: P generation individually housed in steel wire-bottomed cages except during cohabitation and postpartum periods. From day 20 of presumed gestation female rats were housed individually in nesting boxes. Each dam and delivered litter were housed in a common nesting box during postpartum.
- Diet (e.g. ad libitum):ad libitum, Certified Rodent Diet #5002 (PMI Nutrition International)
- Water (e.g. ad libitum):ad libitum, mains sourced and filtered by reverse osmosis.
- Acclimation period:13 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-26
- Humidity (%):30-70
- Air changes (per hr):at least 10
- Photoperiod (hrs dark / hrs light):12/12
IN-LIFE DATES: From: 17 Aug 2009 To: 2 Oct 2009
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: Suspensions of test substance were prepared daily, stored at room temperature and protected from light.
VEHICLE
- Justification for use and choice of vehicle (if other than water): no data
- Concentration in vehicle: 3.125, 6.25, 12.5, 25mg/ml
- Amount of vehicle (if gavage): 4ml/kg
- Lot/batch no. (if required):J-145
- Purity:no data - Details on mating procedure:
- - M/F ratio per cage: 1
- Length of cohabitation: 7 days
- Proof of pregnancy: vaginal plug and/or sperm in vaginal smear referred to as day 0 of pregnancy
- After 7 days of not mated females will be considered to be at day 0 of presumed gestation
- After successful mating each pregnant female was caged individually. Also those female rats in presumed gestation.
- Any other deviations from standard protocol: none - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- by HPLC-UV, validated internal method.
- Duration of treatment / exposure:
- Male rats: total 45 days - from 14days before cohabitation, through cohabitation (7 days) and continuing through the day before sacrifice after completion of the dosage period.
Female rats: total 44 or 45 days - from 14 days before cohabitation, through cohabitation (7 days), and continuing through the day before sacrifice on postpartum day 5, or study day 46 (for rats that did not become pregnant) or gestation day 25 (for rats that did not deliver). Dams with no surviving pups were sacrificed on postpartum day 1.
Pups were not administered the test substance directly but may have been exposed in utero or via maternal milk. - Frequency of treatment:
- Once daily. Dosage volume was adjusted daily on the basis of individual body weights recorded before administration.
- Details on study schedule:
- - No selection of F1 parental animals took place
- Age at mating of the mated animals in the study: approximately 13 weeks for females and 14 weeks for males
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 12.5, 25, 50, 100 mg/kg bw/day
Basis:
actual ingested
- No. of animals per sex per dose:
- 8 animals/sex/dose
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: Results from two 90-day dermal studies.
- Rationale for animal assignment (if not random):random
- Other: none - Positive control:
- none
Examinations
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: at least twice per day
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule:at least weekly during acclimation period; First 5 days of dosage: prior to dosage and at approx. hourly intervals for the first 4 hours after dosage administration, and at the end of day; From day 6 of treatment: prior to dosage administration, 1-2hrs after dosage administration and at the end of the day; Day of sacrifice: once.; Postdosage periods: once daily.
BODY WEIGHT: Yes
- Time schedule for examinations: Acclimation period: at least weekly; Dosage period: daily; On sacrifice day: Once
FOOD CONSUMPTION: Yes; at least weekly for males; For females, at least weekly during acclimation and precohabitation periods, on gestation days 0, 7, 8, 9, 10, 14, 18, 21 and 25, and on postpartum days 1 and 5.
WATER CONSUMPTION No
OTHER: Rats were evaluated for adverse clinical signs observed during parturition, duration of gestation (from day 0 of gestation till the day the first pup was observed), litter sizes (all pups delivered) and pup viability at birth. Maternal behaviour was evaluated on pospartum days 1 and 5. - Oestrous cyclicity (parental animals):
- By examination of vaginal cytology for 14 days before cohabitation, and then until spermatozoa were observed in a smear of the vaginal contents and/or a copulatory plug was observed in situ during the cohabitation period.
- Sperm parameters (parental animals):
- Epididymides, prostate, seminal vesicles and testes were weighed and microscopically evaluated.
- Litter observations:
- STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: no
PARAMETERS EXAMINED
The following parameters were examined in F1 offspring:
number and sex of pups, stillbirths, live births, postnatal mortality, weight gain, clinical observations
GROSS EXAMINATION OF DEAD PUPS:
yes, for external and internal abnormalities; possible cause of death was determined for pups born or found dead. Those that died before examination of the litter for pup viability were evaluated by immersing their lungs in water. Pups with lungs that sunk were identified as stillborn. Pups with lungs that floated were identified as liveborn and to have died shortly after birth. Pups that died before scheduled termination on days 2-5 postpartum were preserved in Bouin's solution for possible future evaluation except when precluded by autolysis. - Postmortem examinations (parental animals):
- SACRIFICE
- Male animals: All surviving animals after completion of cohabitation period on day 46 of treatment.
- Maternal animals: All surviving animals on postpartum day 5, day study 46 or day gestation 25.
GROSS NECROPSY
- Gross necropsy consisted of external and internal examinations including the cervical, thoracic, and abdominal viscera. Uteri of apparently nonpregnant rats were examined, while being pressed between glass plates, to confirm the absence of implantation sites, and were retained in 10% NBF.
HISTOPATHOLOGY / ORGAN WEIGHTS
The following tissues were prepared for microscopic examination and weighed: Epididymides, gross lesions/masses (only histology), ovaries, prostate, seminal vesicles, testes, uterus with cervix. - Postmortem examinations (offspring):
- SACRIFICE
- The F1 offspring at 4 days of age (postpartum day 5).
GROSS NECROPSY
- Gross necropsy consisted of external and internal examinations including a single cross-section of the head at the level of the frontal-parietal suture and examination of the cross-sectioned brain for apparent hydrocephaly. - Statistics:
- Averages and percentages calculated
- Reproductive indices:
- % rats that mated; Fertility index (number of pregnancies/number of rats that mated); % rats mated with female on days 1-7; % Pregnant rats among those cohabited
- Offspring viability indices:
- % delivered litters; number implantation sites per delivered litter; % dams with stillborn pups; Gestation index (number of dams with one or more liveborn pups/number of pregnant rats); % dams with all pups dying days 1-5 postpartum; Viability index (number of live pups on day 5 postpartum/ number of liveborn pups on day 1 postpartum; Surviving pups/litter on day 1 and on day 5; % male pups per number of pups sexed on day 1 and 5; Live litter size at weighing on day 1 and 5; Pup weight/litter on day 1 and 5;
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- no effects observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- only during lactation in females
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- only during lactation in females
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Other effects:
- not examined
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- no effects observed
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- no effects observed
Details on results (P0)
There were no mortalities. All clinical observations were considered unrelated to treatment.
BODY WEIGHT AND FOOD CONSUMPTION (PARENTAL ANIMALS)
Males: body weights and body weight gains, and absolute (g/day) and relative (g/kg/day) feed consumption were generally comparable among the dosage groups.
Females:
Precohabitation - body weights increased during second week compared to control group and overall for the entire premating period (14% greater than controls). These increases were not considered adverse since they didn't persist and there was not corresponding effect on feed consumption. Gestation - Body weights and feed consumption were unaffected by treatment.
Lactation - maternal body weight gains in the 100mg/kg/day were reduced on days 1-5 of lactation, in comparison with control group. Corresponding to reduced body weight gains during the lactation period, feed consumption values in the 100mg/kg/day were reduced in comparison to the vehicle group.
REPRODUCTIVE FUNCTION: ESTROUS CYCLE (PARENTAL ANIMALS)
The number of estrous stages per 14 days was comparable among the five dosage groups during the precohabitation period.
REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS)
All mating and fertility parameters were unaffected at all dosages (fertility index, rats with confirmed mating dates during cohabitation and number of pregnancies per number of rats in cohabitation).
There was an apparent increase in the average number of days to mating and a reduction in % of rats that mated that occurred in the highest dose group. This was attributed to two male rats that did not mate with their cohort rats. These effects were not attributed to treatment for the following reasons: 1) there was no apparent effect on male or female reproductive organ weights; 2) the remaining rats in the 100mg/kg/day dosage group (N=6) mated and had viable litters; 3) there were not apparent effects on natural delivery in this dosage group; and 4) the average value (3.4+/- 2.3 days) was within the historical range of the Testing Facility.
ORGAN WEIGHTS (PARENTAL ANIMALS)
The weights of the epididymides, testes, seminal vesicles (with and without fluid) and prostate and the ratios of these organ weights to terminal body weight were unaffected.
GROSS PATHOLOGY (PARENTAL ANIMALS)
There were no treatment-related gross lesions at any dosage level tested.
HISTOPATHOLOGY (PARENTAL ANIMALS)
None of the microscopic findings that occurred were considered related to the test substance. They were all considered to be incidental or spontaneous changes.
Effect levels (P0)
- Dose descriptor:
- NOAEL
- Effect level:
- >= 100 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No treatment related effects observed
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:
- 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)
No treatment related clinical observations occurred or tretment related necropsy observations. All pups that died early or survived to scheduled sacrificed appeared normal at necropsy.
Effect levels (F1)
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- >= 100 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No treatment related effects observed.
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Any other information on results incl. tables
Table 7.8.1/1: Mating and fertility - summary - P generation male rats
Dosage group |
|
I |
II |
III |
IV |
V |
Dosage (mg/kg/day) |
|
0 (Vehicle) |
12.5 |
25 |
50 |
100 |
Rats in cohabitation |
N |
8 |
8 |
8 |
8 |
8 |
Days in cohabitationa |
Mean ± S.D. |
2.0 ± 1.1 |
3.0 ± 1.3 |
2.6 ± 1.3 [7] |
2.9 ± 1.4 |
3.4 ± 2.3 |
Rats that mated |
N (%) |
8(100.0) |
8(100.0) |
8(100.0) |
8(100.0) |
6( 75.0) |
Fertility indexb |
N/N (%) |
7/ 8 (87.5) |
8/ 8 (100.0) |
7/ 8 (87.5) |
8/ 8 (100.0) |
6/ 6 (100.0) |
Rats with confirmed mating dates |
N |
8 |
8 |
7 |
8 |
6 |
Mated with femalec |
N(%) |
8(100.0) |
8(100.0) |
7(100.0) |
8(100.0) |
6(100.0) |
Rats pregnant/rats in cohabitation |
N/N |
7/ 8 |
8/ 8 |
7/ 8 |
8/ 8 |
6/ 8 |
(%) |
(87.5) |
(100.0) |
(87.5) |
(100.0) |
(75.0) |
[ ] = Number of values averaged
a. Restricted to rats with a confirmed mating date and rats that did not mate.
b. Number of pregnancies/number of rats that mated.
c. Restricted to rats with a confirmed mating date.
Table 7.8.1/2: Estrous cycling, mating and fertility - summary - P generation female rats
Dosage group |
|
I |
II |
III |
IV |
V |
Dosage (mg/kg/day)a |
|
0 (Vehicle) |
12.5 |
25 |
50 |
100 |
Estrous cycling observations |
||||||
Rats evaluated |
N |
8 |
8 |
8 |
8 |
8 |
Precohabitation estrous cycling |
|
|
|
|
|
|
Estrous stages/14 days |
Mean ± S.D. |
3.2 ± 0.7 |
3.5 ± 0.9 |
3.2 ± 0.5 |
3.1 ± 0.8 |
3.5 ± 0.5 |
Rats with 6 or more consecutive days of diestrus |
N(%) |
0(0.0) |
0(0.0) |
0(0.0) |
0(0.0) |
0(0.0) |
Rats with 6 or more consecutive days of estrus |
N(%) |
0(0.0) |
0(0.0) |
0(0.0) |
0(0.0) |
0(0.0) |
Mating observations |
||||||
Rats in cohabitation |
N |
8 |
8 |
8 |
8 |
8 |
Days in cohabitationb |
Mean ± S.D. |
2.0 ± 1.1 |
3.0 ± 1.3 |
2.6 ± 1.3 [ 7] |
2.9 ± 1.4 |
3.4 ± 2.3 |
Rats that mated |
N(%) |
8(100.0) |
8(100.0) |
8(100.0) |
8(100.0) |
6(75.0) |
Fertility indexc |
N/N(%) |
7/ 8( 87.5) |
8/ 8(100.0) |
7/ 7(100.0) |
8/ 8(100.0) |
6/ 6(100.0) |
Rats with confirmed mating dates |
N(%) |
8(100.0) |
8(100.0) |
7(100.0) |
8(100.0) |
6(100.0) |
Rats pregnant/rats in cohabitation |
N/N |
7/ 8 |
8/ 8 |
7/ 8 |
8/ 8 |
6/ 8 |
(%) |
(87.5) |
(100.0) |
(87.5) |
(100.0) |
(75.0) |
[ ] = Number of values averaged
a. Dosage occurred on Day 1 of study through Day 4 of lactation or Day 24 of presumed gestation (rats that did not deliver a litter).
b. Restricted to rats with a confirmed mating date and rats that did not mate.
c. Number of pregnancies/number of rats that mated.
Table 7.8.1/3: Natural delivery observations - summary - P generation female rats
Dosage group |
|
I |
II |
III |
IV |
V |
Dosage (mg/kg/day)a |
|
0 (Vehicle) |
12.5 |
25 |
50 |
100 |
Rats assigned tonatural delivery |
N |
8 |
8 |
8 |
8 |
8 |
Pregnant |
N |
7 |
8 |
7 |
8 |
6 |
Delivered litters |
N(%) |
7(100.0) |
8(100.0) |
7(100.0) |
8(100.0) |
6(100.0) |
Duration of gestationb |
Mean ± S.D. |
22.7 ± 0.5 |
22.8 ± 0.5 |
22.7 ± 0.5[ 6]c |
23.0 ± 0.9 |
22.3 ± 0.5 |
Implantation sitesper delivered litter |
N |
112 |
136 |
116 |
115 |
98 |
|
Mean ± S.D. |
16.0 ± 1.6 |
17.0 ± 1.6 |
16.6 ± 1.6 |
14.4 ± 5.7 |
16.3 ± 1.9 |
Dams with stillborn pups |
N(%) |
1(14.3) |
1(12.5) |
1(14.3) |
1(12.5) |
1(16.7) |
Dams with no liveborn pups |
N |
0 |
0 |
0 |
1 |
0 |
Gestation index
|
% |
100.0 |
100.0 |
100.0 |
87.5 |
100.0 |
N/N |
7/ 7 |
8/8 |
7/ 7 |
7/8 |
6/6 |
|
Dams with all pups dying |
N(%) |
0 |
0 |
0 |
0 |
0 |
a. Dosage occurred on Day 1 of study through Day 4 of lactation.
b. Calculated (in days) as the time elapsed between confirmed mating (arbitrarily defined as Day 0 of gestation) and the day the first pup was delivered.
c. Excludes a value for dam 3460, which did not have a confirmed mating date.
Table 7.8.1/4: Litter observations (naturally delivered pups) - summary - F1 generation litters
Maternal dosage group |
|
I |
II |
III |
IV |
V |
Maternal dosage (mg/kg/day) |
|
0 (vehicle) |
12.5 |
25 |
50 |
100 |
Delivered litters with one or more liveborn pups |
N |
7 |
8 |
7 |
7 |
6 |
Pups delivered (total) |
N |
103 |
132 |
104 |
108 |
89 |
|
Mean ± S.D. |
14.7 ± 1.8 |
16.5 ± 1.4 |
14.8 ± 3.4 |
15.4 ± 1.1 |
14.8 ± 2.8 |
Liveborn |
Mean ± S.D. |
14.6 ± 1.8 |
16.4 ± 1.3 |
14.7 ± 3.4 |
15.3 ± 1.1 |
14.7 ± 2.7 |
|
N(%) |
102(99.0) |
131(99.2) |
103(99.0) |
107(99.1) |
88(98.9) |
Stillborn |
Mean ± S.D. |
0.1 ± 0.4 |
0.1 ± 0.4 |
0.1 ± 0.4 |
0.1 ± 0.4 |
0.2 ± 0.4 |
|
N(%) |
1(1.0) |
1(0.8) |
1(1.0) |
1(0.9) |
1(1.1) |
Pups found dead or presumed cannibalized |
|
|
|
|
|
|
Day 1 |
N/N(%) |
0/102(0.0) |
0/131(0.0) |
0/103(0.0) |
0/107(0.0) |
0/ 88(0.0) |
Days 2- 5 |
N/N(%) |
2/102(2.0) |
0/131(0.0) |
0/103(0.0) |
0/107(0.0) |
6/ 88(6.8) |
Viability indexa |
% |
98.0 |
100.0 |
100.0 |
100.0 |
96.6 |
|
N/N |
100/102 |
131/131 |
103/103 |
107/107 |
85/ 88 |
Delivered litters with one or more liveborn pups |
N |
7 |
8 |
7 |
7 |
6 |
Surviving pups/litter |
|
|
|
|
|
|
Day 1 |
Mean ± S.D. |
14.6 ± 1.8 |
16.4 ± 1.3 |
14.7 ± 3.4 |
15.3 ± 1.1 |
14.7 ± 2.7 |
Day 5 |
Mean ± S.D. |
14.3 ± 1.6 |
16.4 ± 1.3 |
14.7 ± 3.4 |
15.3 ± 1.1 |
13.7 ± 2.4 |
Percent male pups per number of pups sexed |
|
|
|
|
|
|
Day 1 |
Mean ± S.D. |
56.1 ± 17.0 |
52.4 ± 4.3 |
56.8 ± 18.3 |
50.5 ± 17.4 |
48.2 ± 12.5 |
Day 5 |
Mean ± S.D. |
57.0 ± 16.3 |
52.4 ± 4.3 |
56.8 ± 18.3 |
50.5 ± 17.4 |
48.5 ± 11.8 |
Delivered litters with one or more liveborn pups |
N |
7 |
8 |
7 |
7 |
6 |
Live litter size at weighing |
|
|
|
|
|
|
Day 1 |
Mean ± S.D. |
14.6 ± 1.8 |
16.4 ± 1.3 |
14.7 ± 3.4 |
15.3 ± 1.1 |
14.7 ± 2.7 |
Day 5 |
Mean ± S.D. |
14.3 ± 1.6 |
16.4 ± 1.3 |
14.7 ± 3.4 |
15.3 ± 1.1 |
13.7 ± 2.4 |
Pup weight/litter (grams) |
|
|
|
|
|
|
Day 1 |
Mean ± S.D. |
6.3 ± 0.1 |
6.2 ± 0.4 |
6.4 ± 0.5 |
6.5 ± 0.7 |
6.2 ± 0.5 |
Day 5 |
Mean ± S.D. |
9.8 ± 0.7 |
9.3 ± 1.0 |
9.9 ± 1.8 |
9.8 ± 1.2 |
9.2 ± 1.6 |
Day(s) = Day(s) postpartum
a. Number of live pups on Day 5 postpartum/number of liveborn pups on Day 1 postpartum.
Table 7.8.5/5: Maternal body weights - lactation - individual data - P generation female rats
Day |
1 |
2 |
3 |
4 |
5 |
Rat # |
Dosage group: 0 (vehicle) mg/kg bw/day |
||||
3441 |
286 |
287 |
291 |
298 |
309 |
3442 |
322 |
334 |
344 |
339 |
332 |
3443 |
287 |
282 |
289 |
293 |
309 |
3444 |
321 |
328 |
322 |
327 |
337 |
3445 |
285 |
288 |
283 |
285 |
284 |
3446 |
350 |
331 |
336 |
342 |
354 |
3447 |
312 |
318 |
320 |
322 |
322 |
3448 |
Not pregnant |
||||
Rat # |
Dosage group : 100 mg/kg bw/day |
||||
3473 |
Not pregnant; mating not confirmed |
||||
3474 |
290 |
287 |
292 |
293 |
310 |
3475 |
299 |
294 |
298 |
297 |
302 |
3476 |
Not pregnant; mating not confirmed |
||||
3477 |
279 |
273 |
288 |
290 |
284 |
3478 |
351 |
347 |
345 |
344 |
346 |
3479 |
352 |
336 |
324 |
323 |
334 |
3480 |
327 |
323 |
326 |
328 |
338 |
All weights were recorded in grams (g).
Day = Day of lactation
Applicant's summary and conclusion
- Conclusions:
- The NOAEL for fertility effects was 100 mg/kg bw/day or higher under the test conditions of this study.
- Executive summary:
In the dosage-range finding study conducted similarly according to guideline OECD421,rats were given once daily by gavage alpha-hexylcinnamaldehyde (HCA) diluted in corn oil at 12.5, 25, 50 or 100 mg/kg bw or the vehicle alone. The males were treated from 14 days before cohabitation, through mating (maximum of 7 days), and continuing through the day before sacrifice on day 47. The female rats were administered HCA (same dosage as for males) or vehicle two weeks before cohabitation, through mating, and continuing through the day before sacrifice on day. Female rats were allowed to deliver their litters and were sacrificed on postpartum day 5 (PPD 5). F1 generation pups were also sacrificed on PPD 5 (i.e.5thday of lactation). The following parameters were evaluated: viability, clinical observations, body weights, feed weights, mating and fertility, delivery and litter observations, organ weights (epididymides, ovaries, prostate, seminal vesicles, testes, and uterus with cervix), necropsy observations and histopathology (epididymides, ovaries, prostate, seminal vesicles, testes, and uterus with cervix).
All P generation male and female rats survived to scheduled sacrifice. There were no treatment-related clinical observations or gross lesions in the P generation rats of both sexes at any dosage level tested. In addition, none of the microscopic findings examined were considered related to treatment withHCA. Body weights and body weight gains of the treated P generation male rats were generally comparable among the dosage groups. Absolute and relative feed consumption values in male rats were unaffected by treatment withHCAduring the entire dosage period.
In treated P generation female rats, body weight gains were increased (14% by comparison with the vehicle group) during the second week of the pre-cohabitation dosage period in the 100 mg/kg bw/day dosage group, and therefore overall for the entire two-week premating period . These increases in body weight gain were not considered adverse because there was no corresponding effect on feed consumption, and the increase in weight gain did not persist during the gestation period. Body weights and body weight gains of the female rats were unaffected by treatment withHCAduring the gestation period. Absolute and relative feed consumption values were unaffected by treatment withHCAduring the precohabitation and gestation periods.
Therefore, four females out of six have lost body weight up to the fourth day of lactation. Corresponding to reduced body weight gains during the lactation period, feed consumption values (weight in gram during the five days of lactation) in the 100 mg/kg bw/day dosage group were reduced on lactation days 1 to 5, in comparison to the vehicle control group values (84% of controls). The significant decrease in maternal body weight in the 100 mg/kg bw/day dose group during the lactation period showed that this dose level can be considered as the maximum tolerated dose (MTD).
Terminal body weights and male and female reproductive organ weights were comparable among the five dosage groups. There was no effect ofHCAon estrous cycling. There was no effect on mating and fertility (fertility index, gestation index, number of implantation sites) at any dosage level tested. All recorded pregnant rats (7, 8, 7, 8 and 6 females in the five respective dosage groups from the control group to the highest dose group) delivered a litter. Natural delivery and litter observations (duration of gestation, number and sex of offspring per litter, stillbirths, live births, gross alterations, litter size and viability, viability index, lactation index, percent survival, sex ratio, pup body weights) were unaffected by dosages ofHCAas high as 100 mg/kg bw/day. No treatment-related clinical or necropsy (including a single cross-section of the head and examination of the cross-sectioned brain for apparent hydrocephaly) observations occurred in the F1 generation pups. As such, no developmental effects were observed.
.
The NOAEL for maternal and developmental toxicity was 100 mg/kg bw/day or greater,
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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