Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
14 May 2019 - 30 May 2019
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2019
Report Date:
2019

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Specific details on test material used for the study:
Batch No TRODBB06

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
Six Sprague Dawley rats (SPF Caw), supplied by Elevage JANVIER LABS (53940 Le Genest St Isle – France), 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.

Group treated (2000 mg/kg): 3 female rats Rf3782 to Rf3784 (Step 1)
3 female rats Rf3786, Rf3788 to Rf3791 (Step 2)
One animal (Rf3787) presenting signs of incorrect gavage the day of the administration was replaced by the animal Rf3791.

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 (ENVIGO - 2016) 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 every six months by Bureau Veritas – Eurofins (FRANCE).

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
As no information was available regarding a possible systemic toxicity of the test item, the first test dose was 2000 mg/kg body weight.
The animals of the treated group received an effective dose of 2000 mg/kg body weight of the test item Acetic acid, oxo-, sodium salt, reaction products with ethanolamine and phenol, sodium hydroxide and ferric chloride (MEAHA Fe).
Distilled water was chosen as it produced the most suitable formulation at the requested concentration.
In the first step of the study, 2.0013 g of the test item were weighed and distilled water was added to a flask q.s. 10 mL.
In the second step of the study, 2.0008 g of the test item were weighed and distilled water was added to a flask q.s. 10 mL.
Just before the administration, the preparations were stirred using a vortex for 30 seconds to obtain dark red solutions.
Each preparation was administered under a volume of 10 mL/kg body weight using a suitable syringe graduated fitted with an oesophageal metal canula.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6
Control animals:
yes
Remarks:
Three animals, received the control item Distilled water, administered by gavage under a volume of 10 mL/kg body weight using a suitable syringe graduated fitted with an oesophageal metal canula.
Details on study design:
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.
On day 14, the animals were eathanized and macroscopic observations were entered on individual autopsy sheets.

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 Acetic acid, oxo-, sodium salt, reaction products with ethanolamine and phenol, sodium hydroxide and ferric chloride (MEAHA Fe) 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 Acetic acid, oxo-, sodium salt, reaction products with ethanolamine and phenol, sodium hydroxide and ferric chloride (MEAHA Fe) 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.
Executive summary:

The test item Acetic acid, oxo-, sodium salt, reaction products with ethanolamine and phenol, sodium hydroxide and ferric chloride (MEAHA Fe) was administered to a group of 6 female Sprague Dawley rats at the dose of 2000 mg/kg body weight.

The experimental protocol was established according to the official method as defined in the O.E.C.D. Test Guideline No. 423 dated December 17th, 2001.

No mortality occurred during the study.

No clinical signs related to the administration of the test item were observed during the study.

The body weight evolution of the animals remained normal during the study.

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

In conclusion, the LD50 of the test item Acetic acid, oxo-, sodium salt, reaction products with ethanolamine and phenol, sodium hydroxide and ferric chloride (MEAHA Fe) 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 Acetic acid, oxo-, sodium salt, reaction products with ethanolamine and phenol, sodium hydroxide and ferric chloride (MEAHA Fe) 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.