Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2018-01-17 to 2017-04-30
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
dated 17 December 2001
Deviations:
yes
Remarks:
Environmental parameters : relative humidity lower than 30% (minimum = 25%) - this deviation is considered without impact on the conclusion of the study.
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
dated 30 May 2008
GLP compliance:
yes (incl. certificate)
Remarks:
dated 27 April 2017
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Elevage JANVIER LABS, Le Genest St Isle, France
- Age at study initiation: 8 weeks old at the beginning of the study
- Weight at study initiation: 188 - 208 g
- Fasting period before study: Food was removed on day -1 and then redistributed 4 hours after adminsitration of the test item.
- Housing: Animals were housed by group of three in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid. Each cage contains sawdust and was installed in conventional air conditioned animal husbandry
- Diet (ad libitum): Envigo - 2016
- Water: ad libitum, tap-water from public distribution system
- Acclimatization period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature: 19 - 25 °C
- Relative humidity: 30 - 70 %
- Photoperiod (hrs dark / hrs light): 12/12
- Rate of air exchange : at least 10 changes per hour

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 1.75 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
No. of animals per sex per dose:
3 + 3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- 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 symptonms, recorded as 'present' or 'absent'. These observations were compared to historical control data. Clinical observations and mortality were recorded every day for 14 days.
- Periodical examinations: The animals were weighed on 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 anesthetised with sodium pentobarbital (Dolethal). 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 levelsopen allclose all
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
< 5 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
2 500 mg/kg bw
Based on:
test mat.
Remarks on result:
other: calculation - LD50 cut-off of the test item
Mortality:
Two mortalities (2/6) were noted in animals treated at 2000 mg/Kg body weight on day 4 (step 1) or day 3 (step 2) post-dose.
Clinical signs:
The mortalities were preceded by an absence of spontaneous activity (2/2), muscle tones (1/2), Preyer's reflex (1/2), righting reflex (2/2) associated with piloerection (2/2).
In the surviving animals (4/6), a decrease of spontaneous activity (4/4) and Preyer's reflex (2/4) associated with piloerection (1/4) was noted during the first hours of the tests. The animals recovered a normal activity on day 1.
Body weight:
An absence of body weight gain wzd noted on day 2 versus day 0. Then, the body weight evolution of the animals remained normal.
Gross pathology:
The macrosscopic examination of the animals died during the study revealed a thinning of corpus and cellular lyse (2/2).
The macroscopic examinations of the animals at the end of the study (surviving animals) did not reveal treatment related changes.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 of the test item is higher than 2000 mg/kg body weight and lower than 5000 mg/Kg body weight by oral route in the rat.
In accordance with the OECD Test Guideline n° 423, the LD50 cut-off of the test item may be considered as 2500 mg/Kg body weight by oral route in the rat.
The test item does not have to be classified in accordance with the Regulation EC n° 1272/2008 on classification, labelling and packaging of substances and mixtures. No signal word or hazard statement is required.