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Administrative data

Description of key information

The acute oral toxicity study with Titanium(4+) tetrakis(2-ethyl-3-hydroxyhexan-1- olate), Tyzor OGT in Wistar rats was conducted to assess the toxicological profile of the test item. The prepared dose formulation mixed with corn oil and was administered as a single oral gavage to overnight fasted (16 to 18 hours) three female rats (G1-FTS) at the dose of 300 mg/kg body weight. There were no clinical signs or mortality. Hence, three additional female rats were tested at the same dose of 300 mg/kg body weight (G1-STS). There were no clinical signs or mortality, as per the scheme - Annex 2c of the guideline, the treatment was initiated with the next higher dose of 2000 mg/kg bodyweight (G2-FTS). There were no clinical signs or mortality. Hence three additional female rats were tested at the same dose of 2000 mg/kg body weight (G2-STS). There were no clinical signs or mortality, no further test was required as per the scheme - Annex 2c of the OECD 423 guideline, hence the dosing was stopped. The rats were observed for mortality and clinical signs for 14 days post treatment. Body weights were recorded prior to dosing on day 1 and again on days 8 and 15. Necropsy was performed for all the rats at termination. All survived rats gained weight during experimental period. There were no gross pathological changes at necropsy. Based on the results of the present study, The LD50 of the test item, Tyzor OGT is 5000 mg/kg or unclassified as per the GHS. The test item is classified “Category 5” or Unclassified as per Globally Harmonized Classification system of Annex 2c of the Guideline, OECD 423.

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:
12 March 2018-17 April 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
Source: In-Vivo Biosciences
Kodigehalli Village
Magadi Road, Bangalore, Code-29
Karnataka State

No. of groups : Two treatment groups – 4 steps (G1-FTS, G1-STS, G2-FTS & G2-STS)

Age at treatment: 9 to 11 weeks

Rats were housed under standard laboratory conditions, air conditioned with adequate fresh air supply (13.8 air changes/hour). Environment: with temperature 20 to 24°C, relative humidity 64 to 67%, with 12 hours light
and 12 hours dark cycle.

Rat & Mice pellet feed, manufactured by Krishna Valley Agro Tech LLP, MIDC Kupwad block, Sangli, Maharashtra, was provided to animals.

Deep bore-well water passed through activated charcoal filter and exposed to UV rays in Aquaguard on-line water filter-cum-purifier manufactured by Eureka Forbes Ltd, Mumbai 400 001, India, was provided to animals in polycarbonate bottles with stainless steel sipper tubes.
Route of administration:
oral: gavage
Vehicle:
corn oil
Doses:
No toxicological information was available for the test item. Hence, the study was initiated with the starting dose of 300 mg/kg body weight (G1 FTS). As there was no mortality at the dose of 300 mg/kg, the test was continued with three additional animals with the same dose of 300 mg/kg body weight (G1-STS). There was no mortality at the dose of 300 mg/kg, the test was continued with three additional animals with the next higher dose of 2000 mg/kg body weight (G2- FTS). As there was no mortality at the dose of 2000 mg/kg, the test was continued with three additional animals with the same dose of 2000 mg/kg body weight (G2-STS). The subsequent dosing was done at approximately 48 - 72 hours after the first treatment step.
No. of animals per sex per dose:
Three
Control animals:
no
Details on study design:
The prepared test item dose formulation was administered at the dose volume of 10 mL/kg bodyweight to attain the dose of 300 (G1 – First treatment step & G1 – Second treatment step) and 2000 mg/kg body weight
(G2 – First treatment step & G2 – Second treatment step) as a single oral gavage to overnight fasted rats (16 to 18 hours). Each animal was administered orally by gavage using disposable plastic syringe attached
with metal feeding cannula. Food was offered about 3 to 4 hours after dosing. Water was not withheld.

Clinical signs and pre-terminal deaths

At each step, the animals were observed five times on test day 1 (day of administration) i.e. at 30 minutes and four times at hourly intervals and once daily during days 2 to 15 post administration. Observations included changes in skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern. Attention was directed to the observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma and all observed clinical signs were recorded.

The body weights were recorded on test day 1 (pre-administration), day 8 (7 days post administration) and day 15 (14 days post administration).

The rats surviving to the end of the observation period were euthanised by using isoflurane anaesthesia and subjected to detailed necropsy. Gross pathological findings were recorded and reported. Microscopic examination was not carried out as no gross pathological changes were observed.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
5 000 mg/kg bw
Based on:
test mat.
Mortality:
G1 - [300 mg/kg body weight - Treatment (FTS and STS)]: No mortality.
G2 - [2000 mg/kg body weight - Treatment (FTS and STS)]: No mortality.
Clinical signs:
G1 - [300 mg/kg body weight - Treatment (FTS and STS)]: No clinical signs were observed.
G2 - [2000 mg/kg body weight - Treatment (FTS and STS)]: No clinical signs were observed.
Body weight:
G1 - [300 mg/kg body weight - Treatment (FTS and STS)]: All the rats gained body weight throughout the observation period.
G1 - [2000 mg/kg body weight - Treatment (FTS and STS)]: All the rats gained body weight throughout the observation period.
Gross pathology:
There were no gross pathological changes at necropsy.
Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results of the present study, The LD50 of Titanium(4+) tetrakis(2-ethyl-3-hydroxyhexan-1- olate), Tyzor OGT, is 5000 mg/kg or unclassified as per the GHS.
Executive summary:

The acute oral toxicity study with Titanium(4+) tetrakis(2-ethyl-3-hydroxyhexan-1- olate), Tyzor OGT, in Wistar rats was conducted to assess the toxicological profile of the test item. The prepared dose formulation mixed with corn oil and was administered as a single oral gavage to overnight fasted (16 to 18 hours) three female rats (G1-FTS) at the dose of 300 mg/kg body weight. There were no clinical signs or mortality. Hence, three additional female rats were tested at the same dose of 300 mg/kg body weight (G1-STS). There were no clinical signs or mortality, as per the scheme - Annex 2c of the guideline, the treatment was initiated with the next higher dose of 2000 mg/kg bodyweight (G2-FTS). There were no clinical signs or mortality. Hence three additional female rats were tested at the same dose of 2000 mg/kg body weight (G2-STS). There were no clinical signs or mortality, no further test was required as per the scheme - Annex 2c of the OECD 423 guideline, hence the dosing was stopped. The rats were observed for mortality and clinical signs for 14 days post treatment. Body weights were recorded prior to dosing on day 1 and again on days 8 and 15. Necropsy was performed for all the rats at termination. All survived rats gained weight during experimental period. There were no gross pathological changes at necropsy. Based on the results of the present study, The LD50 of the test item, Tyzor OGT is 5000 mg/kg or unclassified as per the GHS. The test item, Tyzor OGT is classified as follows:The test item is classified “Category 5” or Unclassified as per Globally Harmonized Classification system of Annex 2c of the Guideline, OECD 423.

  • The test item does not meet the criteria for classification as “Category 4” (300 mg/kg < Acute Toxicity Estimates ≤ 2000 mg/kg) as per Regulation (EC) No 1272/2008 of the European Parliament and of the council of 16 December 2008 on classification, labeling and packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 1999/45/EC, and amending Regulation (EC) No 1907/2006, as there was no mortality observed at 300 and 2000 mg/kg body weight.
  • The test item is classified as “Category 5” (the oral LD50 range of 2000 to 5000 mg/kg) as per OECD: Harmonised Integrated Classification system (OECD, 2001), as there was no mortality observed at 300 and 2000 mg/kg body weight.
  • The test item is classified as “Category 5” (2000 mg/kg < Acute Toxicity Estimates ≤ 5000 mg/kg) as per Globally Harmonized System of Classification and Labeling of Chemicals (GHS) Seventh Revised Edition, United Nations (2017). ST/SG/AC.10/30/Rev.7, as there was no mortality observed at 300 and 2000 mg/kg body weight.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
Klimisch score 1

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Based on the results of the present study, The LD50 of Titanium(4+) tetrakis(2-ethyl-3-hydroxyhexan-1- olate) Tyzor OGT is 5000 mg/kg and unclassified as per the GHS.