Sodium 5-oxo-1-palmitoyl-L-prolinate

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

24.February.1998-10.March.1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Specific details on test material used for the study:

Test material:
Identification, reference: CS80602
Batch: 98034300
Appearance: white paste
Quantity received, packaging: 100 g, plastic jar
Date of receipt: february 11, 1998
Laboratory reference: 98-0437
Analytical sheet: not supplied
Homogeneity test: not required for less than 28 days studies
Storage: at room temperature, away from the light

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Reason for species selection : the Rat is the animal chosen by the regulatory authorities to evaluate the safety of drugs and chemicals.
Number and sex : 10 animals: 5 males and 5 females
Age, weight: about 6 weeks, weight between 183 g and 204 g (males) and 167 g and 178 g (females) at the beginning of the study.
Acclimatization: at least 5 days
Housing, diet: 5 animals by sex in polypropylene cages (310 x 465 x 190) in accordance with the requirements of the 86/609/EEC guideline. Complete pelleted rat maintenance diet UAR A04-10 (91360 - EPINAYSURORGE, FRANCE).

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

The day before the test, animals have been fasted prior to substance administration by withholding food and the product was placed at a temperature of 40°C in order to liquefy it. The next day, they received by gavage, according to the bodyweight, the product diluted with distilled water (Meram batch 62421) at the single dose of 2000 mg/kg under a constant volume of 5 ml/kg. The administered preparation was kept up under magnetic stirring during the treatments.
Reason for route of administration: Oral gavage is the route of choice for estimating potential adverse effects resulting from accidental oral ingestion.

Doses:

2000 mg/kg under a constant volume of 5 ml/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

The animals were observed daily for 14 days after the treatment.

Clinical examinations:
- a clinical observation was carried out at least once a day in order to evaluate the general appearance, the behaviour and vegetative functions of the animals. An individual clinical observation was realized one hour after treatment. The continuous observations during the five following hours were renewed each following day.
- body weights were taken just prior to the test material administration (D1) and again on days 4, 8 and 15.

Macroscopic examinations:
At termination of the 14 observation days, the rats were sacrificed after barbituric anaesthesia, then autopsied. All abnormalities were recorded.
No tissue was saved.

Preliminary study:

no

Key result

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred

Clinical signs:

other: During the first hour following the treatment, a slight piloerection was observed in all the animals. During the 5 following hours, no modification in the aspect, behaviour or vegetative functions was observed. The daily examinations which were repeated t

Gross pathology:

The gross necropsy of the animals 14 days after the treatment did not show any visible organic or tissular lesions leading us to suspect a possible systemic toxicity of the product. Under the experimental conditions adopted, the oral LD0 of the test material CS80602 in male and female Rat is higher than 2000 mg/kg.

Interpretation of results:

GHS criteria not met

Conclusions:

The single oral administration of the preparation CS80602 in the male and female Rat at the dose of 2000 mg/kg:
- did not cause any death, - had no significant toxic effect on the animals' behaviour or vegetative functions, - did not modify their weight growth, - did not cause any gross lesion visible at autopsy.
Under the experimental conditions adopted, oral LD0 of the test preparation is higher than 2000 mg/kg in the Rat.
According to the 67/548/EEC directive, the test preparation is unclassified ifswallowed.

Executive summary:

The single oral administration of the preparation CS80602 in the male and female Rat at the dose of 2000 mg/kg:

• did not cause any death,


• had no significant toxic effect on the animals' behaviour or vegetative functions,


• did not modify their weight growth,


• did not cause any gross lesion visible at autopsy.

Under the experimental conditions adopted, oral LD0 of the test preparation is higher than 2000 mg/kg in the Rat.

According to the 67/548/EEC directive, the test preparation is unclassified if swallowed.

 

In conclusion, the LD50 of the test item LCA08009 is higher than 2000 mg/kg body weight by dermal 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 item LCA08009 must not be classified. No symbol and risk phrase are required. In accordance with the Globally Harmonized System (COM(2007)355 final), the test item must not be classified in category 4.

No signal word and hazard statement are required.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

27.May.2008-10.June.2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Specific details on test material used for the study:

• Sponsor’s identification: LCA08009 • Date received : 14 May 2008
• Container : plastic flask (n=1) • Form : liquid
• Quantity : 142.44 g (container + contents) • Colour : brown
• Batch n° : LCA08009 • Storage : room temperature
• Production date: - • Expiry date: -
• CAS No: - • Purity: 30% It was identified under the code number: PH-08/0227.

The test item was considered as 100% for the study.
Informations concerning the identity, purity and stability of the test item are the responsibility of the Sponsor. A safety data sheet and an information data sheet concerning the test item were provided by the study monitor.

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Animals:
Twenty 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 226 g and 248 g (males) and between 185 g and 222 g (females) and were 7-8 weeks old.
Group 1 (control): 5 male rats Rm0722 to Rm0726 and 5 female rats Rf0727 to Rf0731
Group 2 (treated): 5 male rats Rm0752 to Rm0756 and 5 female rats Rf0757 to Rf0761

Housing:
During the treatment, the animals were kept in individual cage. At D3, the animals were put into their cage by 2 or 3. The 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 21°C - relative humidity : between 39% and 55% - lighting time: 12 hours daily - rate of air exchange: at least ten changes per hour

Food and drink:
Drinking water (tap-water from public distribution system) and foodstuff were supplied freely. 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.).

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Dose and administration mode
Animals from Group 2 received by topical application, under porous gauze dressing, an effective dose of 2000 mg/kg body weight of LCA08009, administered under a volume of 2.05 mL/kg body weight, during 24 hours. After 24-hour exposure period, the gauze dressings were removed and the treated area was rinsed with distilled water.
Animals from Group 1 received in the same experimental conditions the control item (liquid paraffin) under a volume of 2 mL/kg body weight.

Duration of exposure:

24 hours

Doses:

Group 1: control item (liquid paraffin) under a volume of 2mL/kg body weight
Group 2: 2000 mg/kg body weight under a volume of 2.05 mL/kg body weight

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

Examinations of the animals

Daily examination
Systematic examinations were carried out to identify any behavioural or toxic effects on the major physiological functions 5 days after administration of the test solution. 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.

Periodical examinations
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.

Examination at the end of the test
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.

Statistics:

no data

Preliminary study:

no preliminary study performed

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study.

Clinical signs:

other: No systemic clinical signs related to the administration of the test item were observed. It was noted a slight to moderate erythema, on the treated area, 24 hours after the test item administration in all treated animals. The treated areas have recovere

Gross pathology:

The macroscopical examination of the animals at the end of the study did not reveal treatment-related changes.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 of the test item LCA08009 is higher than 2000 mg/kg body weight by dermal 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 item LCA08009 must not be classified. No symbol and risk phrase are required. In accordance with the Globally Harmonized System (COM(2007)355 final), the test item must not be classified in category 4. No signal word and hazard statement are required.

Executive summary:

The test item LCA08009 was applied onto the intact skin of 10 Sprague Dawley rats (5 males and 5 females) 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° 402 dated February 24th, 1987 and the test method B.3 of the directive. n° 92/69/EEC.

No mortality occurred during the study.

No systemic clinical signs related to the administration of the test item were observed. It was noted a slight to moderate erythema, on the treated area, 24 hours after the test item administration in all treated animals. The treated areas have recovered a normal aspect between D3 (male) and D11 (female). The body weight evolution of the animals remained normal throughout the study, similar between treated and control animals.

The macroscopical examination of the animals at the end of the study did not reveal treatment-related changes.

In conclusion, the LD50 of the test item LCA08009 is higher than 2000 mg/kg body weight by dermal 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 item LCA08009 must not be classified. No symbol and risk phrase are required. In accordance with the Globally Harmonized System (COM(2007)355 final), the test item must not be classified in category 4.

No signal word and hazard statement are required.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Justification for classification or non-classification

The single oral administration of the preparation CS80602 in the male and female Rat at the dose of 2000 mg/kg:

- did not cause any death, - had no significant toxic effect on the animals' behaviour or vegetative functions, - did not modify their weight growth, - did not cause any gross lesion visible at autopsy.

Under the experimental conditions adopted, oral LD0 of the test preparation is higher than 2000 mg/kg in the Rat.

According to the 67/548/EEC directive, the test preparation is unclassified ifswallowed.