Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
Six Sprague Dawley rats (SPF Caw) were used after an acclimatization period of at least five days. The animals were nulliparous and non-pregnant. At the beginning of the study, the animals were 8 weeks old.
They were identified prior to inclusion in the test by means of a numbered ring on the edge of one ear.

Housing:
Healthy female rats were housed by group of three 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 temperature and relative humidity of the main test were controlled to remain within target ranges of 19°C to 25°C and 30% to 70%, respectively. The rate of air exchange was at least ten changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (07.00 to 19.00) and twelve hours darkness.

Food and drink:
Drinking water (tap-water from public distribution system) and foodstuff were supplied ad libitum. Food was removed on D-1 and then redistributed 4 hours after the test item administration.
Microbiological and chemical analyses of the water were carried out once evry six months.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
In the first and second step of the study, the test item was administered by gavage under a volume of 1.81 mL/kg body weight (corresponding to 2 g/kg, according to the calculated density) using a suitable graduated syringe fitted with an oesophageal metal canula.
Doses:
2000 mg/kg bw/d
No. of animals per sex per dose:
6 female rats were administered 2000 mg test substance/kg bw/d.
Control animals:
no
Details on study design:
Daily examination:
Systematic examinations were carried out to identify any behavioural or toxic effects on the major physiological functions during 14 days following the administration of the test item. This examination focuses particularly on a list of symptoms, recorded as "present" or "absent" on the observation sheet. These observations were compared to historical 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 euthanized with sodium pentobarbital. Macroscopic observations were entered on individual autopsy sheets. Only those organs likely to be modified in cases of acute toxicity were examined. No organ was removed and preserved in view to microscopic examinations.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study.
Clinical signs:
No clinical signs related to the administration of the test item were observed during the study.
Body weight:
The body weight evolution of the animals remained normal during the study.
Gross pathology:
The macroscopic examination of the animals at the end of the study did not reveal treatment related changes.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In conclusion, the LD50 of the test item Whey, lactose-low (EC 295-893-9) is higher than 2000 mg/kg body weight. In accordance with the O.E.C.D. Test Guideline No. 423, the LD50 cut-off of the test item may be
considered as 5000 mg/kg body weight by oral route in the rat.
The test item Whey, lactose-low (EC 295-893-9) does not have to be classified in accordance with the Regulation EC No. 1272/2008 on classification, labelling and packaging of substances and mixtures.
No signal word or hazard statement is required.