Dodecanal

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Link to relevant study records

Reference

Endpoint:

one-generation reproductive toxicity

Remarks:

based on test type (migrated information)

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Study period:

No data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

A valid study is available for the analogue substance, Heptanoic acid. The study meets generally accepted scientific standards with acceptable restrictions for the standard test. The read-across is considered to be suitable based on the structural and “mechanistic action” similarities between the target substance (Dodecanal) and source substance (Heptanoic acid) and their similar physico-chemical properties.

Qualifier:

according to guideline

Guideline:

other: Unclear; makes reference to FDA (1987)

Deviations:

not specified

GLP compliance:

yes

Limit test:

yes

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

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

Remarks:

Doses / Concentrations:
200 mg/kg bw/d
Basis:
no data

Remarks:

Doses / Concentrations:
1000 mg/kg bw/d
Basis:
no data

Remarks:

Doses / Concentrations:
2000 mg/kg bw/d
Basis:
no data

No. of animals per sex per dose:

10 females per dose

Control animals:

yes, concurrent vehicle

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

Clinical signs:

effects observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Organ weight findings including organ / body weight ratios:

not examined

Histopathological findings: non-neoplastic:

not examined

Reproductive function: oestrous cycle:

not examined

Reproductive function: sperm measures:

not examined

Reproductive performance:

not examined

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.

Dose descriptor:

NOAEL

Effect level:

200 mg/kg bw/day

Based on:

test mat.

Sex:

female

Dose descriptor:

LOAEL

Effect level:

1 500 mg/kg bw/day

Based on:

test mat.

Sex:

female

Clinical signs:

no effects observed

Mortality / viability:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Sexual maturation:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

no effects observed

Histopathological findings:

not examined

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.

Reproductive effects observed:

not specified

Conclusions:

The test substance was assessed for toxicity to reproduction usign a one-generation study in teh rat. 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.
A valid study is available for the analogue substance, Heptanoic acid. The study meets generally accepted scientific standards with acceptable restrictions for the standard test. The read-across is considered to be suitable based on the structural and “mechanistic action” similarities between the target substance (Dodecanal) and source substance (Heptanoic acid) and their similar physico-chemical properties.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

200 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Short description of key information:
One generation studies were performed using analogue substances 2,6-dimethylhept-5-enal and Heptanoic acid. The NOAEL was 300 mg/kg bw/day and 200 mg/kg bw/day respectively.

Justification for selection of Effect on fertility via oral route:
The No Observed Adverse Effect Level (NOAEL) for adult toxicity, reproduction and offspring survival, growth and development was considered to be 200 mg/kg bw/day.

Effects on developmental toxicity

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Toxicity to reproduction: other studies

Additional information

The test substance was assessed for toxicity to reproduction using a one-generation study in rats using the analogue substances 2,6-dimethylhept-5-enal and Heptanoic acid. The results showed that under the conditions of the test, dose levels of 300 mg/kg bw/day of 2,6-dimethylhept-5 -enal and dose levels of 200 mg/kg bw/day of Heptanoic acid had no adverse effects on the reproductive performance of female Sprague-Dawley rats or the growth or development of their offspring.

Justification for classification or non-classification

According to Directive 67/548/EEC and Regulation (EC) 1272/2008, no classification is warranted.