Nonanoic acid

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Study period:

11 May 1982 to 24 June 1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

1982

Report date:

1982

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Deviations:

yes

Remarks:

: minor deviations and some deficiencies in data reporting

GLP compliance:

not specified

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Nonanoic acid

EC Number:

203-931-2

EC Name:

Nonanoic acid

Cas Number:

112-05-0

Molecular formula:

C9H18O2

IUPAC Name:

nonanoic acid

Details on test material:

- Name of test material (as cited in study report): C-182 (nonanoic acid)
- Purity: > 96% (see attached document)
- Substance type: clear colourless liquid
- Physical state: liquid
- Storage condition of test material: at room temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories Inc. New York
- Age at study initiation: about 14 weeks
- Weight at study initiation: 230.5 +/-17.9 g
- Housing: individually, 2 females per male during mating
- Diet (ad libitum): Purina Rodent Laboratory chow
- Water (ad libitum): tap water
- Acclimation period: about 9 weeks


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24.4 +/- 0.5
- Humidity (%): 57 +/- 4.8
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
The amount of compound required was weighed and diluted with vehicle, dosing was performed from stirred dilutions

Analytical verification of doses or concentrations:

no

Details on mating procedure:

- Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: 1/2
- Length of cohabitation: maximum of three weeks
- Verification of same strain and source of both sexes: yes
- Proof of pregnancy: vaginal plug or sperm in vaginal smear referred to as day 0 of pregnancy

Duration of treatment / exposure:

gd 6 - 15

Frequency of treatment:

1x/d

Duration of test:

9 days

Doses / concentrations

Remarks:

Doses / Concentrations:
1500 mg/kg bw/day in corn oil
Basis:
nominal conc.

No. of animals per sex per dose:

22

Control animals:

yes, concurrent vehicle

Details on study design:

Administered dose was based on individual body weights from the most recent weighing interval and approximately the same time each day.

Examinations

Maternal examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: once daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: once daily

BODY WEIGHT: Yes
- Time schedule for examinations: on days 0, 6, 9, 12, 15 and 50 of gestation

FOOD AND WATER CONSUMPTION. Yes
- Time schedule for examinations: on days 6-8, 9-11, 12-14, 15-17, 18-20

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20
- Organs examined: gross examination of all internal organs, detailed examination of ovaries (see below)

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes

Fetal examinations:

- External examinations: Yes: all per litter
- Soft tissue examinations: Yes: about one-third per litter
- Skeletal examinations: Yes: about two-third per litter
- Head examinations: Yes: [all per litter / half per litter / #? per litter ] / No / No data
- Body weights and crown-rump distance: Yes

Statistics:

The following statistic tools were used:
National Cancer Institute Package; Box's test for homogeneity of variance, followed by one-way ANOVA and Dunnett's T-test; test of multiple proportions; Fisher's exact test

Indices:

Mean incidence of visceral anomalies: group mean of [(number fo fetuses with anomalies per litter/number of fetuses examined viscerally per litter) x 100]
Mean incidence of visceral variants: group mean of [(number fo fetuses with variants per litter/number of fetuses examined viscerally per litter) x 100]
Mean incidence of skeletal anomalies: group mean of [(number fo fetuses with anomalies per litter/number of fetuses examined viscerally per litter) x 100]
Mean incidence of skeletal variants: group mean of [(number fo fetuses with variants per litter/number of fetuses examined viscerally per litter) x 100]

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:no effects

Details on maternal toxic effects:
There were no compound-related maternal effects (body weight gain, food and water consumption, gross pathology).

Effect levels (maternal animals)

Key result

Dose descriptor:

NOAEL

Effect level:

1 500 mg/kg bw/day

Basis for effect level:

other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
Skeletal variants and delayed ossification (both 38.2%) were identical to the values of the control group (38.2%). No statistically significant compound-related skeletal anomalies were noted: Of a selection of 80 fetuses from 22 litters, there were two instances of cleft palate, two with small tongue, and a single incidence of hydroureter that were not seen in control fetuses.

Effect levels (fetuses)

1

Key result

Dose descriptor:

NOAEL

Effect level:

1 500 mg/kg bw/day

Basis for effect level:

other: teratogenicity

2

Key result

Dose descriptor:

NOAEL

Effect level:

1 500 mg/kg bw/day

Basis for effect level:

other: fetotoxicity

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

Summarised results (maternal body weights, ovarian, uterine and litter data, fetal examinations) are presented in the attached document.

Applicant's summary and conclusion

Conclusions:

Under the conditions of this developmental study there were no effects with respect to dams or offspring.

Executive summary:

22 female Sprague-Dawley rats were treated orally by gavage with 1500 mg/kg bw/day of the test item on days 6 -15 of gestation in a developmental toxicity test. The 22 control animals received the vehicle corn oil. After the sacrifice at day 20 of gestation no adverse effects could be observed in the exposed dams. There were no differences between the offspring of treated and control rats with respect to teratogenic or fetotoxic effects (resorptions, viability, fetal weights, skeletal or visceral malformations or variations). Therefore the NOAEL of this study is 1500 mg/kg bw/day for dams and offspring (Celanese/Hazleton, 1983).