Reaction products of tetraisopropyl titanate (4+), hydroxyalkaloic acid and substituted alkanol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From September 16th, 2020 to October 2nd, 2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2020

Report date:

2020

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

Adopted: 17th December 2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Test material form:

solid

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Institute of Experimental Pharmacology and Toxicology, Center of Experimental Medicine of the Slovak Academy of Sciences, Dobrá Voda, Slovak
Republic
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8-12 weeks
- Weight at study initiation:
- Fasting period before study: fasted prior to dosing (food but not water was withheld over-night). After the test item administration, food was withheld
for further 3 - 4 hours.
- Housing: The animals were housed in plastic cages suspended on stainless steel racks, up to 3 animals per cage, in a room equipped with central air
conditioning.
- Diet (e.g. ad libitum): ad libitum. Standard laboratory food KKZ-P/M (UEFT CEM SAS).
- Water (e.g. ad libitum): The animals received tap water for human consumption. Supply of drinking water was unlimited. The quality of drinking water is periodical monitored (including microbiological control) and recorded.
- Acclimation period: at least 5 days prior to the start of treatment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2 °C
- Humidity (%): 55 ± 10 %.
- Photoperiod (hrs dark / hrs light): 12-hour light / 12-hour dark cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Aqua pro injectione

Details on oral exposure:

VEHICLE
- Justification for choice of vehicle: Ultra pure water such as API is a common vehicle for water soluble items in toxicity studies like OECD TG 423
- Lot/batch no. (if required): 19144011

DOSAGE PREPARATION (if unusual): The required amount of the test item (according to the body weight and dose) was mixed with appropriate vehicle (Aqua pro injectione) shortly before administration. Dose was recalculated to concentration 100 % of Titanium Glycolate Monoethanolamine (purity of test item was > 99 %).

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 per step

Control animals:

no

Details on study design:

The starting dose can be selected from the fixed dose levels of 5, 50, 300, and 2000 mg/kg body weight. Available information indicated that the test item was likely to be non-toxic regarding acute toxicity therefore we chose a dose of 2000 mg of test item per kg body weight to be used as a starting dose. In the first step, one group of 3 females was dosed. The test item in limit dose did not cause mortality for 48 hours and therefore, in a second step, another 3 females were treated
at the same dose level.
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: the animals were observed individually immediately after the administration of the test item and then 0.5, 1, 2 and 4 hours later. Each animal was inspected daily for the next 14 days. Individual weights of animals were determined shortly before the test item administration and
weekly thereafter. Weight changes after first and second week after administration were calculated and recorded.
- Necropsy of survivors performed: yes. All test animals were subjected to gross necropsy.
- Examinations performed: clinical signs, body weight, pathology. Observations included: changes in skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous systems, and somatomotor activity and behavioural patterns. Attention was directed to observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

other: No signs of intoxication, change of health, nor any other adverse reactions during 24 hours and 14-days observation period at limit dose of 2000 mg/kg body weight was observed. Animals No 1-3 exhibit slight piloerection after 2 hours from administration a

Gross pathology:

No visible pathological findings were observed in animals dosed with 2000 mg/kg body weight.

Applicant's summary and conclusion

Interpretation of results:

other: not classified as harmful/toxic according to the CLP Regulation (EC) No. 1272/2008

Conclusions:

LD50 (female rats) > 2000 mg/kg bw

Executive summary:

The purpose of the study was to evaluate the potential toxic effect of the test item “Titanium Glycolate Monoethanolamine” when administered as a single oral dose to Wistar rats. The procedure according to OECD Guideline 423 Acute Toxic Class (ATC) method was used.

A limit dose of 2000 mg/kg body weight was used as a starting dose. Available information indicated that the test item is likely to be non-toxic regarding acute toxicity, therefore, a limit dose of 2000 mg/kg body weight was used as a starting dose.

In the first step, one group of 3 females was dosed. The test item at this dose did not cause death in the next 48 hours and therefore another 3 females were treated at the same dose level. The test item administered to 6 females Wistar rats at a limit dose of 2000 mg/kg did not induce signs of intoxication, change of health, nor any other adverse reactions during 14-days observation period. During necropsy no macroscopic findings were observed in all animals at this dose level. The body weights of all animals increased in normal range during the study.The LD50 of the test item is greater than 2000 mg/kg body weight after single oral administration to Wistar rats. Based on Annex 2d Test Procedure with a Starting Dose of 2000 mg/kg body weight of OECD Guideline 423 it can be concluded that the test item Titanium Glycolate Monoethanolamine is classified in GHS Category 5 – Unclassified. Limit test with dose of 5000 mg/kg body weight was not conducted.