trans-1-(1-oxohexadecyl)-4-[(1-oxohexadecyl)oxy]-L-proline

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Remarks:

combined repeated dose and reproduction / developmental screening

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2012

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)

GLP compliance:

yes (incl. QA statement)

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

trans-1-(1-oxohexadecyl)-4-[(1-oxohexadecyl)oxy]-L-proline

EC Number:

255-490-0

EC Name:

trans-1-(1-oxohexadecyl)-4-[(1-oxohexadecyl)oxy]-L-proline

Cas Number:

41672-81-5

Molecular formula:

C37H69NO5

IUPAC Name:

1-palmitoyl-4-(palmitoyloxy)-L-proline

Details on test material:

See section 7.8.1

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

see section 7.8.1

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

see section 7.8.1

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

about 1 month for male and 54 days for females. See section 7.8.1

Frequency of treatment:

daily

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
100 mg/kg bw/d
Basis:
other: nominal concentration

Doses / concentrations 2

Remarks:

Doses / Concentrations:
300 mg/kg bw/d
Basis:
other: nominal concentration

Doses / concentrations 3

Remarks:

Doses / Concentrations:
1000 mg/kg bw/d
Basis:
other: nominal concentration

No. of animals per sex per dose:

Main groups : 10 males+10 females per group
Recovery groups : 5 males + 5 females per group
Total = 100 (50 males + 50 females)

Control animals:

yes, concurrent vehicle

Details on study design:

see section 7.8.1

Examinations

Observations and examinations performed and frequency:

see section 7.8.1

Sacrifice and pathology:

see section 7.8.1

Statistics:

see section 7.8.1

Results and discussion

Results of examinations

Details on results:

see section 7.8.1

Effect levels

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no significant effect noted

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

To summarize, oral administration of test item “ trans-1-(1-oxohexadecyl)-4-[(1-oxohexadecyl)oxy]-L-proline” to Wistar rats at the dose levels 100, 300 and 1000 mg/kg Bwt/day had no effects on general health, body weights, food intake, pre-coital time, gestation length, mating and fertility parameters. Functional observations did not reveal any test item related changes at all the tested doses in both sexes. The live birth and survival index was not altered by the treatment at the entire tested dose. The test item administration did not reveal any treatment related changes in the hematology, coagulation and clinical chemistry parameters of both males and females. There were no test item related changes in the terminal body weights, organ weights and organs weight ratios in both males and females. Gross examination of pups on lactation day 4 did not reveal any gross changes.
There were no test item related gross and microscopic changes in both males and females

No Observed Adverse Effect Level (NOAEL):
As there were no adverse effects observed in any parameters up to the highest dose tested, the No Observed Adverse Effect Level (NOAEL) is considered to be 1000 mg/kg Bwt/day.

Executive summary:

Under experimental conditions described in the Material and Method section, the following results were obtained:

No clinical signs or mortality was observed during the course of the study.

No treatment-related neurological abnormalities /dysfunctions were observed at all the doses tested.

The body weights and food consumption were unaffected by the treatment at all the doses tested.

The body weights and food consumption were unaffected during gestation and lactation periods at all the doses tested.

There were no treatment-related changes in the hematology, coagulation and clinical chemistry parameters.

Treatment had no effect on pre-coital time or gestation length, mating and fertility parameters in both sexes.

There were no treatment-related effects on the uterine/implantation data, mean litter size and mean viable litter size.

There were no external abnormalities in live or dead pups in any of the groups.The Day 4 survival index was not altered by the treatment at all the doses tested.

The test item administration did not reveal any treatment related changes in the hematology, coagulation and clinical chemistry parameters of both males and females.

There were no test item related changes in the terminal body weights, organ weights and organs weight ratios in both males and females. Gross examination of pups on lactation day 4 did not reveal any gross changes.

There were no test item related gross and microscopic changes in both males and females.

No Observed Adverse Effect Level (NOAEL): As there were no adverse effects observed in any parameters up to the highest dose tested, the No Observed Adverse Effect Level (NOAEL) is considered to be 1000 mg/kg Bwt/day.