Decanal

Toxicity to reproduction

Administrative data

Endpoint:

one-generation reproductive toxicity

Type of information:

experimental study

Adequacy of study:

key study

Study period:

No data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study meets generally accepted scientific standards with acceptable restrictions for the standard test.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Unnamed

Year:

1990

Report date:

1990

Reference 2

Reference Type:

secondary source

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Unclear; makes reference to FDA (1987)

Deviations:

not specified

GLP compliance:

yes

Remarks:

no details specified

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Heptanoic acid

EC Number:

203-838-7

EC Name:

Heptanoic acid

Cas Number:

111-14-8

Molecular formula:

C7H14O2

IUPAC Name:

heptanoic acid

Details on test material:

- Name of test material (as cited in study report): Aldehyde, 5-heptenal, 2,6-dimethyl
- Molecular formula: C₇H₁₄O₂
- Molecular weight: 310.079
- Smiles notation: O=C(O)CCCCCC
- InChl: InChI=1S/C7H14O2/c1-2-3-4-5-6-7(8)9/h2-6H2,1H3,(H,8,9)
- Structural formula attached as image file
- Substance type: No data
- Physical state: No data
- Analytical purity: No data
- Impurities (identity and concentrations): No data
- Composition of test material, percentage of components: No data
- Isomers composition: No data
- Purity test date: No data
- Lot/batch No: No data
- Expiration date of the lot/batch: No data
- Stability under test conditions: No data
- Storage condition of test material: No data

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: No data
- Age at study initiation: No data
- Weight at study initiation: No data
- Fasting period before study: No data
- Housing: No data
- Diet (e.g. ad libitum):No data
- Water (e.g. ad libitum):No data
- Acclimation period:No data
- Other: Nulliparous

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on exposure:

DIET PREPARATION
- Rate of preparation of diet (frequency): No data
- Mixing appropriate amounts with (Type of food):No data
- Storage temperature of food: No data

VEHICLE
- Justification for use and choice of vehicle: No data
- Concentration in vehicle: No data
- Amount of vehicle: 5 mL/kg bw/d

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

1 week treatment followed by 7 d cohabitation period through gestation, parturition and 4-d postpartum period.

Frequency of treatment:

Daily

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

200 mg/kg bw/day (nominal)

Doses / concentrations 2

Dose / conc.:

1 000 mg/kg bw/day (nominal)

Doses / concentrations 3

Dose / conc.:

2 000 mg/kg bw/day (nominal)

No. of animals per sex per dose:

10 females per dose

Control animals:

yes, concurrent vehicle

Examinations

Parental animals: Observations and examinations:

CAGE-SIDE OBSERVATIONS
- Viability was monitored twice daily during the study.
- Rats were observed daily for clinical signs approx. 30 mins after gavage administration.

BODY WEIGHT
- Measurement of body weight was performed weekly.

FOOD CONSUMPTION
- Food consumption measurement was also conducted weekly during the premating/premating period and then on days 0, 6, 14, 16, 21, and 25 of gestation and on days 1 and 4 of lactation/postparturition.

MATING PERFORMANCE
- Mating performance was evaluated daily during the cohabitation period.
- Dams were evaluated daily during gestation for duration of gestation, maternal behaviour, litter size and pup viability.

Oestrous cyclicity (parental animals):

Mating, day 0 of gestation identified on basis of spermatozoa in vaginal smear.

Postmortem examinations (parental animals):

SACRIFICE
- Dams that did not deliver litters were sacrificed on day 25 of presumed gestation and dams that did deliver litters were sacrificed on days 4 or 5 of lactation. All dams were examined for gross lesions and implantation sites.

GROSS NECROPSY
- Ovaries from all dams and any observed gross lesions were preserved in neutral 10% formalin for possible evaluation.

Postmortem examinations (offspring):

GROSS NECROPSY
- Vital signs at birth were determined for pups that were stillborn or died before the initial examination of the litter.
- Each litter was evaluated for viability a minimum of twice daily during the 4-day lactation period.
- Dead pups were removed and necropsied.
- Tissues with gross lesions were preserved for possible examination.
- Pups in each litter were counted and observed for nursing behaviour and physical abnormalities daily.
- Pup body weights were measured on days 1 and 4 of postpurition.

Statistics:

Fisher's ANOVA followed by Dunnett's test

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

effects observed, treatment-related

Dermal irritation (if dermal study):

no effects observed

Mortality:

mortality observed, treatment-related

Description (incidence):

MORTALITY
- 1 and 3 deaths were reported in the 1000 and 2000 mg/kg bw/day dose groups, respectively.

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Food efficiency:

effects observed, treatment-related

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

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)

MORTALITY
- 1 and 3 deaths were reported in the 1000 and 2000 mg/kg bw/day dose groups, respectively.

CLINICAL SIGNS
- Clinical signs at 200 mg/kg bw/day in dams during premating and gestation included a significant increase in rales (P<0.01). This effect was not
reported during the lactation period. In the 1000 and 2000 mg/kg bw/day dose group, significant increases in the incidence of rales (P<0.01), excess salivation (P<0.01) was reported during premating and gestation. Excess salivation continued during lactation in the high-dose group.
- Other significant (P<0.01) effects during gestation in the high-dose group included decreased activity, ungroomed coat and labored breathing.

BODY WEIGHTS
- The 2000 mg/kg bw/day group showed reduced body weight gains during premating, and significantly (P<0.05 to <0.01) decreased average maternal body weights on days 10 and 16 of gestation.

FOOD CONSUMPTION
- Average and relative food consumption was reduced in the high-dose group of dams throughout the study. The high dose also was associated with reduced mating and fertility that were related to mortality.

COHABITATION INDICES
-The duration of cohabitation and fertility and gestation indices 200, 1000, or 2000 mg/kg bw/day were not different from comparable indices in thee control group.

Effect levels (P0)

1

Key result

Dose descriptor:

NOAEL

Effect level:

300 mg/kg bw/day

Based on:

test mat.

Sex:

female

Basis for effect level:

mortality

2

Key result

Dose descriptor:

LOAEL

Effect level:

1 500 mg/kg bw/day

Based on:

test mat.

Sex:

female

Basis for effect level:

mortality

Results: F1 generation

General toxicity (F1)

Clinical signs:

no effects observed

Dermal irritation (if dermal study):

not examined

Mortality / viability:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Sexual maturation:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

no effects observed

Histopathological findings:

not examined

Other effects:

not examined

Developmental neurotoxicity (F1)

Behaviour (functional findings):

not examined

Developmental immunotoxicity (F1)

Developmental immunotoxicity:

not examined

Details on results (F1)

BODY WEIGHT
- The high-dose group exhibited reduced pup weights on day 4 postparturition.

OTHER
No biologically relevant or statistically significant differences in the number of implantations, duration of gestation, the percentage of dams delivering one or more live pups, and the pup viability index were observed.

GROSS PATHOLOGY
- No malformations or gross lesions were observed in pups at any dose levels.

Effect levels (F1)

Key result

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

200 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

organ weights and organ / body weight ratios

Overall reproductive toxicity

Key result

Reproductive effects observed:

no

Lowest effective dose / conc.:

1 000 mg/kg bw/day (nominal)

Treatment related:

yes

Applicant's summary and conclusion

Conclusions:

The test substance was assessed for toxicity to reproduction in a one-generation test, using rats exposed to the test substance via oral gavage. Dose levels of 200 mg/kg bw/day of heptanoic acid had no significant adverse effects on the reproductive performance of female Sprague-Dawley rats or the growth or development of their offspring.