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

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2008-03-05 to 2008-04-17

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

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:

- form: powder
- colour : white
- batch number: 0713500014
- re test date: 2010 May 14
- Storage: room temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

Twelve Sprague Dawley rats (SPF Caw) originated from Elevage JANVIER (53940 Le Genest St Isle– France), were used after an acclimatisation period of at least five days. At the beginning of the study, the animals of the treated group weighed between 195 g and 218 g and were 8 weeks old.Three healthy female rats were kept in solid-bottomed clear polycarbonate cages with a stainless steel
mesh lid. Each cage contains sawdust bedding which was changed at least 2 times a week. Each cage
was installed in conventional air conditioned animal husbandry; the environmental conditions were:
- temperature : between 19°C and 24°C
- relative humidity : between 42% and 60%
- lighting time: 12 hours daily
Drinking water (tap-water from public distribution system) and foodstuff were supplied freely. Food was removed at D-1 and then redistributed 4 hours after the test item administration.
Microbiological and chemical analyses of the water were carried out once every six months by the Institut Européen de l'Environnement de Bordeaux (I.E.E.B.).

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

The treated animals, received an effective dose of 2000 mg/kg body weight of the test substance, diluted in olive oil and administered by gavage under a volume of 10 mL/kg body weight using a suitable syringe graduated fitted with an oesophageal metal canula.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

- 6 female rats for the control group
- 6 female rats for the treated group

Control animals:

yes

Details on study design:

The treated animals, received an effective dose of 2000 mg/kg body weight of the test substance, diluted in olive oil and administered by gavage under a volume of 10 mL/kg body weight using a suitable syringe graduated fitted with an oesophageal metal canula.
The animals of control group, received, according to the same experimental conditions, the control item (distilled water) under a volume of 2 mL/kg body weight.
Systematic examinations were carried out to identify any behavioural or toxic effects on the major physiological functions 14 days after administration of the test substance.
This examination focuses particularly on a list of symptoms, recorded as "present" or "absent" on the observation sheet.
These observations were compared to control data.
Observations and a mortality report were then carried out every day for 14 days.
The animals were weighed on day D0 (just before administering the test item) then on D2, D7, and D14.
Weight changes were calculated and recorded.
On D14, the animals were anaesthetised with sodium pentobarbital and administration continued to fatal levels. Macroscopic observations were entered on individual autopsy sheets.
Only those organs likely to be modified in cases of acute toxicity were examined. Those presenting macroscopic anomalies can be removed and preserved in view to microscopic examinations.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortality occurred during the study.

Clinical signs:

other: No clinical signs related to the administration of the test item were observed.

Any other information on results incl. tables

The test substance was administered by oral route to a group of 6 female Sprague Dawley rats at the single dose of 2000 mg/kg body weight. The experimental protocol was established on the basis of the official method as defined in the O.E.C.D. guideline N° 423 dated December 17th, 2001 and the test method B.1tris of the Directive N° 2004/73/EC. No mortality occurred during the study. No clinical signs related to the administration of the test item were observed. The body weight evolution of the animals remained normal throughout the study, similar between treated and control animals. The macroscopical examination of the treated animals at the end of the study did not reveal treatmentrelated changes. In conclusion, the LD50 of the test item LCA08001 is higher than 2000 mg/kg body weight by oral route in the rat. In accordance with the OECD guideline n°423, the LD50 of the test item may be considered higher than 5000 mg/kg body weight by oral route in the rat. According to the criteria for classification, packaging and labelling of dangerous substances and preparations in accordance with the E.E.C. Directives 67/548, 2001/59 and 99/45, the test substance must not be classified. No symbol and risk phrase are required.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 of the test substance is higher than 2000 mg/kg body weight by oral route in the rat.
In accordance with the OECD guideline n°423, the LD50 of the test item may be considered higher than 5000 mg/kg body weight by oral route in the rat.
According to the criteria for classification, packaging and labelling of dangerous substances and preparations in accordance with the E.E.C. Directives 67/548, 2001/59 and 99/45, the test substance must not be classified. No symbol and risk phrase are required.

Executive summary:

The test substance was administered by oral route to a group of 6 female Sprague Dawley rats at the single dose of 2000 mg/kg body weight. The experimental protocol was established on the basis of the official method as defined in the O.E.C.D. guideline N° 423 dated December 17th, 2001 and the test method B.1tris of the Directive N° 2004/73/EC. No mortality occurred during the study. No clinical signs related to the administration of the test item were observed. The body weight evolution of the animals remained normal throughout the study, similar between treated and control animals. The macroscopical examination of the treated animals at the end of the study did not reveal treatmentrelated changes. In conclusion, the LD50 of the test item LCA08001 is higher than 2000 mg/kg body weight by oral route in the rat. In accordance with the OECD guideline n°423, the LD50 of the test item may be considered higher than 5000 mg/kg body weight by oral route in the rat. According to the criteria for classification, packaging and labelling of dangerous substances and preparations in accordance with the E.E.C. Directives 67/548, 2001/59 and 99/45, the test substance must not be classified. No symbol and risk phrase are required.