Glutens, hydrolyzates, reaction products with lauroyl chloride, sodium salts

Endpoint summary

Description of key information

Test material: the liquid marketed product "Proteol OAT" which contains ca.27.5% of the solid substance "Glutens, hydrozylates, reaction products with lauroyl chloride, sodium salts".

No hazard was identified after one administration by oral or dermal route in rodents according to OECD n° 401 and 402.

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:

1998-02-24 to 1998-03-10

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD guideline, GL study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Specific details on test material used for the study:

• Identification, reference: PROTEOL OAT - Batch 97 255 001
• Appearance : yellowish liquid
• Purity:28,7% dry matter
• Quantity received, packaging : 250 ml, plastic bottle
• Date ofreceipt : February 09, 1998
• Analytical sheet : reported in appendix
• 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:

- Species, strain, supplier : Albino Rat, Sprague Dawley 0M, IFFA-CREDO (69210 - L’ARBRESLE, FRANCE).
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 189 g and 208 g (males) and 172 g and 187 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 - EPINAY SUR ORGE, FRANCE).

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

Animais have been fasted prior to substance administration by withholding food overnight.
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.

Doses:

2000 mg / kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Observations
The animals were observed daily for 14 days after the treatment.
Clinical observations:
-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 the termination of the 14 observation days, the rats were sacrified after barbituric anaesthesia, then autopsied. All abnormalities were recorded.

Statistics:

no statistic

Preliminary study:

No preliminary study

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: No modification in the aspect, behaviour or vegetative functions was observed in the animals, 1 hour after the treatment or during the 5 following hours, excepted a slight piloerection visible during the first hour following the ingestion of the product.

Gross pathology:

The gross necropsy of the animaIs 14 days after the treatment did not show any visible organic or tissular lesions leading us to suspect a possible systemic toxicity ofthe product.

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the experimental conditions adopted, the oral LD0 of the test material PROTEOL OAT - Batch 97 255 001 in male and female Rat is higher than 2000 mg/kg.
According to the 67/548/EEC directive, the test preparation is unclassified if swallowed

Executive summary:

the single oral administration of the preparation PROTEOL OAT-Batch 97 255 001 in the male and female Rat at the dose of 2000 mg/kg:

- Did not induce 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 LD50 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

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

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:

2008-06-03 to 2008-06-17

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study, OECD guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal 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:

Sponsor's identification: LCE08088
Container: plastic flask
Quantity: 1056,60 g (container+contents)
Batch: 0801000014
Form: liquid
Colour: yellow
Storage: room temperature

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Twenty Sprague Dawley rats (SPF Caw) originated from Elevage JANVIER (53940 Le Genest St Isle
— France), were used alter an acclinatisation period of at least five days. At the beginning of the study,
the animals of the treated group weighed between 225 g and 247 g (males) and between 197 g and
212 g (females) and were 7-8 weeks old,
Group 1 (control)
5 male rats and 5 female rats
Group 2 (treated):
5 male rats and 5 female rats


Housing
During the treatment, the animais 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 ieast 2 times a week. Each cage was installed in conventional air conditioned animal husbandry; the environmental conditions were:
- temperature between 19°C and 23°C
- relative humidity : between 41% and 69%
- 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 systein) 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 (LE.E.B.).

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Animais from Group 2 received by topical application, under porous gauze dressing, an effective dose of 2000 mg/kg body weight of LCE08088, administered under a volume of 1.92 mL/kg body weight, during 24 hours. After 24-hour exposure period, the gauze dressings were removed.
Animals from Group 1 received in the same experimentaI conditions the control item (liquid paraffin) under a volume of 2.32 mL/kg body weight.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

DaiIy examinination
Systematic examinations were carried out to identify any behavioural or toxic effects on the ma]or physiological functions 5 days after administration of the test solution.
This examination focuses particularly on a list of symptoms, recorded as “present” or “absent’1 on the observation sheet.
These observations were conmpared to control data.
Observations and a mortality report were then carried out every day for 14 days.

Periodical examinations
The animais 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 D 14, 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.

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 well defined erythema, on the treated area, 24 hours after the test item administration in all treated animals, The treated areas have recovered a norm

Gross pathology:

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

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 of the test item LCE08088 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 LCE08088 must not be classifled. 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 LCE08088 was applied onto the intact skin of 10 Sprague Dawley rats (5 maies and 5 femaies) 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 112e test method B. 3 ofthe directive. n° 92/69/EEC.

No mortality occured during the study.

No systemic clinical signs related to the administration of the test item were observed. It was noted a well deflned erythema, on the treated area, 24 hours afler the test hem administration in ail treated animais. The treated areas have recovered a normal aspect between D4 (maie) and D8 (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 LCE08088 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 LCE08088 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 registered substance is not classified for health (except for local toxicity)