Nonanamide, N,N-dimethyl-

Toxicity to reproduction

Administrative data

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Study period:

16/10/2017 - 04/05/2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

1

Reference substance name:

N,N-dimethylnonanamide

EC Number:

612-975-5

Cas Number:

6225-08-7

Molecular formula:

C11H23NO

IUPAC Name:

N,N-dimethylnonanamide

Details on test material:

- Name of test material (as cited in study report): N,N-Dimethylnonanamide
- Synonyme: Genagen PA

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Duration of treatment / exposure:

males for 41 days including two weeks pre-mating;
females for two weeks pre-mating period, during mating, during pregnancy and up to lactation day 13

Frequency of treatment:

daily

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 mg/kg bw/day

Doses / concentrations 2

Dose / conc.:

100 mg/kg bw/day

Doses / concentrations 3

Dose / conc.:

300 mg/kg bw/day

Doses / concentrations 4

Dose / conc.:

1 000 mg/kg bw/day

No. of animals per sex per dose:

12

Control animals:

yes, concurrent vehicle

Details on study design:

Males were treated for two weeks pre-mating, during mating and up to the day before sacrifice during post-mating period (total of 41 days of treatment). The females were treated for two weeks pre-mating period, during mating, pregnancy (gestation) and up to lactation day 13 after which the pups were sacrificed on lactation day 13 and females (dams) were sacrificed on lactation day 14 after overnight fasting (water allowed).

Results and discussion

Results: P0 (first parental generation)

Details on results (P0)

All the tested dose group animals of either sex did not reveal any clinical signs of toxicity and no mortality/morbidity observed. There were no changes observed in mean body weight, percent change in body weight with respect to day 1 and feed consumption at all the tested dose group animals of either sex during the experimental period.
No treatment related changes in ophthalmoscopic examination and organ weights (both absolute and relative) were observed at all the tested dose group animals. There were no treatment related changes observed in serum T4 levels of adult males and in serum T4 levels of lactation day 13 pups at any of the tested dose groups.
Dams did not reveal any treatment related changes in oestrus cyclicity, copulatory interval, body weights and feed consumption during gestation and lactation periods, gestation length, live birth index, number of pups, sex ratio and pup survival index at all the tested dose groups throughout the lactation period.
All pups did not reveal any clinical signs or external anomalies throughout the lactation period. No treatment related changes in pup weights, ano-genital distance ratio were noted. No occurrences of nipples in male pups at any of the tested dose groups and vehicle control group.
There were no gross pathological changes (both external and internal) observed at all the tested dose group adult animals and pups.
There were no treatment related histopathological findings noticed during the microscopic examination. Testes were screened with special emphasis on stages of spermatogenesis and interstitial testicular cell structure, revealed normal progression of the spermatogenic cycle and presence of all germ layers (cells). In addition this, ovaries did not show any pathological findings/lesions.

Effect levels (P0)

Key result

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No adverse effect up to the highest dose level

Target system / organ toxicity (P0)

Critical effects observed:

no

Results: F1 generation

Details on results (F1)

All the tested dose group animals of either sex did not reveal any clinical signs of toxicity and no mortality/morbidity observed. There were no changes observed in mean body weight, percent change in body weight with respect to day 1 and feed consumption at all the tested dose group animals of either sex during the experimental period.
No treatment related changes in ophthalmoscopic examination and organ weights (both absolute and relative) were observed at all the tested dose group animals. There were no treatment related changes observed in serum T4 levels of adult males and in serum T4 levels of lactation day 13 pups at any of the tested dose groups.
Dams did not reveal any treatment related changes in oestrus cyclicity, copulatory interval, body weights and feed consumption during gestation and lactation periods, gestation length, live birth index, number of pups, sex ratio and pup survival index at all the tested dose groups throughout the lactation period.
All pups did not reveal any clinical signs or external anomalies throughout the lactation period. No treatment related changes in pup weights, ano-genital distance ratio were noted. No occurrences of nipples in male pups at any of the tested dose groups and vehicle control group.
There were no gross pathological changes (both external and internal) observed at all the tested dose group adult animals and pups.
There were no treatment related histopathological findings noticed during the microscopic examination. Testes were screened with special emphasis on stages of spermatogenesis and interstitial testicular cell structure, revealed normal progression of the spermatogenic cycle and presence of all germ layers (cells). In addition this, ovaries did not show any pathological findings/lesions.

Effect levels (F1)

Key result

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

1 000 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No adverse effect up to the highest dose level

Target system / organ toxicity (F1)

Critical effects observed:

no

Overall reproductive toxicity

Reproductive effects observed:

no

Applicant's summary and conclusion

Conclusions:

The reproduction toxicity of the registration substance Genagen PA/N.N-Dimethylnonamide was evaluated according to the Guideline OECD 421. No significant effect was found up to the highest dose of 1000 mg/kg bw. The NOAEL of 1000 mg/kg bw/day was obtained.

Executive summary:

The reproduction toxicity of the registration substance Genagen PA/N.N-Dimethylnonamide was evaluated according to the Guideline OECD 421.

Female rats were treated daily during 14 days of pre-mating, mating, gestation and 13 days of lactation. Males were treatmend for 41 days including 14 days of premating. The applied doses were 0. 100, 300 and 1000 mg/kg/day. 

No significant effect was found up to the highest dose of 1000 mg/kg bw. The NOAEL of 1000 mg/kg bw/day was obtained.