Bis[[2,2',2''-nitrilotris[ethanolato]](1-)-N,O]bis(propan-2-olato)titanium

Endpoint summary

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

chronic toxicity: oral

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Justification for type of information:

According to hydrolysis test results, this substance is hydrolytically unstable with hydrolysis rate estimated to be less than 30 minutes. The hydrolysis products have been identified to be 2-propanol, triethanolamine and titanium dioxide. The discussion of toxicological properties is based on the hydrolysis/degradation products.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

chronic

Species:

rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Link to relevant study records

Reference

Reference 1

Endpoint:

short-term repeated dose toxicity: inhalation

Data waiving:

exposure considerations

Justification for data waiving:

a short-term toxicity study does not need to be conducted because exposure of humans via inhalation in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment

Justification for type of information:

The substance is a viscous liquid with viscosity over 25000 mPa.s at 25°C. Limited risk of inhalation. Animal testing cannot be justified

Reference 2

Endpoint:

sub-chronic toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)

Deviations:

no

GLP compliance:

yes

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: no vehecle

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

6 hours per day, 5 days per week

Dose / conc.:

100 ppm

Dose / conc.:

500 ppm

Dose / conc.:

1 500 ppm

Dose / conc.:

5 000 ppm

Dose descriptor:

NOAEC

Effect level:

ca. 5 000 ppm

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

Critical effects observed:

no

Conclusions:

Repeated exposure to propan-2-ol produced toxic effects only at 5000 ppm (12300mg/m3)

Endpoint conclusion

Endpoint conclusion:

no study available

Dose descriptor:

NOAEC

12 300 mg/m³

Study duration:

subchronic

Species:

rat

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records

Reference

Reference 1

Endpoint:

short-term repeated dose toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Justification for type of information:

According to hydrolysis test results, this substance is hydrolytically unstable with hydrolysis rate estimated to be less than 30 minutes. The hydrolysis products have been identified to be 2-propanol, triethanolamine and titanium dioxide. The discussion of toxicological properties is based on the hydrolysis/degradation products.

Reference 2

Endpoint:

sub-chronic toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Qualifier:

according to guideline

Guideline:

EU Method B.28 (Sub-Chronic Dermal Toxicity Test: 90-Day Repeated Dermal Dose Study Using Rodent Species)

GLP compliance:

yes

Limit test:

no

Species:

mouse

Strain:

C3H

Sex:

male/female

Details on test animals or test system and environmental conditions:

The animals were housed individually in suspended stainless-steel wire cages in a room with controlled lighting. Certified diet (Agway, Ithaca, USA) and water from an automatic watering system were provided ad lib.

Type of coverage:

open

Vehicle:

acetone

Details on exposure:

Test substances were applied using an Eppendorf automatic pipette, 50μl per application, to the back of each mouse from which the fur was clipped once weekly. The tip of the pipette was used to spread the test substance from the interscapular area to the lumbar area of each mouse.

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

3 times a week for 13 weeks

Dose / conc.:

140 mg/kg bw/day (nominal)

Remarks:

male

Dose / conc.:

460 mg/kg bw/day (nominal)

Remarks:

male

Dose / conc.:

2 000 mg/kg bw/day (nominal)

Remarks:

male

Dose / conc.:

160 mg/kg bw/day (nominal)

Remarks:

female

Dose / conc.:

540 mg/kg bw/day (nominal)

Remarks:

female

Dose / conc.:

2 300 mg/kg bw/day (nominal)

Remarks:

female

No. of animals per sex per dose:

15

Control animals:

no

Clinical signs:

no effects observed

Description (incidence and severity):

No clinical signs of toxicity or skin irritation were observed during the study.

Dermal irritation:

no effects observed

Mortality:

mortality observed, non-treatment-related

Description (incidence):

A vehicle control male, a high-dose male and a low-dose femal died during the study.
These deaths were considered unrelated to TEA treatment.

Body weight and weight changes:

no effects observed

Key result

Dose descriptor:

NOAEL

Effect level:

> 2 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male

Basis for effect level:

clinical signs

Key result

Dose descriptor:

NOAEL

Effect level:

> 2 300 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

female

Basis for effect level:

clinical signs

Key result

Critical effects observed:

no

Conclusions:

When TEA was applied to the skin of mice 3 times per week for 95 days, mild epidermal hyperplasia was observed without evidence of systemic toxicity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

250 mg/kg bw/day

Study duration:

chronic

Species:

rat

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No studies were conducted on the target substance. As the target substance hydrolyses rapidly (half-life < 30 minutes) the intrinsic properties are related to hydrolysis products of the target substance, 2-propanol and triethanolamine (TEA).

 

Repeated dose toxicity of triethanolamine

Dermal

Dermally, there were no signs of systemic toxicity in studies amongst rats and mice of up to 90 days duration with exposure levels up to 2000 mg/kg/day in rats and 4000 mg/kg/day in mice. There were signs of local irritation (mild hyperplasia) at approximately 125 mg/kg/day and above. Systemic NOAEL was set 250 mg/kg bw/day (rats).

 

Oral

For repeated oral exposure, the most reliable studies amongst rats and mice indicate that a NOAEL is of the order of 1000 mg/kg/day (for studies up to 90 days duration). Above this exposure level some signs of systemic toxicity are apparent, being manifested by unspecified changes to the liver and kidney. Administration by drinking water gave NOAELs of 2400 mg/kg/day or more amongst rats and mice in a 14 day study.

(OECD SIDS 1995)

 

 

Repeated dose toxicity of 2-propanol

Inhalation

The observed NOAEC was 5000 ppm (12 300mg/m3) based on a subchronic inhalation study on rat (Burleigh-Flayer, et al. 1994).

 

Justification for classification or non-classification

Based on the NOAEL (oral), NOAEC (inhalation) and NOAEL (dermal) of triethanolamine, there is no need for classification of the target substance in accordance with the criteria of CLP Regulation.