Titanium tetrapropanolate

Endpoint summary

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Reference 1

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 5 minutes. The hydrolysis products have been identified to be 1-propanol and titanium dioxide. The discussion of toxicokinetics is based on the hydrolysis/degradation products.

Reference 2

Endpoint:

chronic toxicity: oral

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:

other: other

Principles of method if other than guideline:

single dose

GLP compliance:

not specified

Limit test:

yes

Species:

rat

Strain:

not specified

Sex:

male

Route of administration:

oral: drinking water

Vehicle:

water

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

4 months

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Key result

Dose descriptor:

NOAEL

Effect level:

ca. 3 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male

Basis for effect level:

clinical signs

Key result

Critical effects observed:

no

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

3 000 mg/kg bw/day

Study duration:

chronic

Species:

rat

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Reference 1

Endpoint:

short-term repeated dose toxicity: inhalation

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 5 minutes. The hydrolysis products have been identified to be 1-propanol and titanium dioxide. The discussion of toxicokinetics is based on the hydrolysis/degradation products.

Reference 2

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Remarks:

authority reviewed.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)

Principles of method if other than guideline:

Study followed intent of OECD 412 with only 9 exposures in 12 days.

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

6 hr/day, 4 days/week up to 2 weeks. (9 exposure days)

Dose / conc.:

246 mg/m³ air

Dose / conc.:

1 230 mg/m³ air

Dose / conc.:

2 460 mg/m³ air

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

slightly swollen periocular tissue, and minimal perinasal and periocular encrustations in the 1000 ppm (2460 mg/m3) exposure concentration group

Key result

Dose descriptor:

NOAEC

Effect level:

ca. 1 230 mg/m³ air

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

1 230 mg/m³

Study duration:

subacute

Species:

rat

Repeated dose toxicity: inhalation - local effects

Link to relevant study records

Reference

Reference 1

Endpoint:

short-term repeated dose toxicity: inhalation

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 5 minutes. The hydrolysis products have been identified to be 1-propanol and titanium dioxide. The discussion of toxicokinetics is based on the hydrolysis/degradation products.

Reference 2

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Remarks:

authority reviewed.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)

Principles of method if other than guideline:

Study followed intent of OECD 412 with only 9 exposures in 12 days.

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

6 hr/day, 4 days/week up to 2 weeks. (9 exposure days)

Dose / conc.:

246 mg/m³ air

Dose / conc.:

1 230 mg/m³ air

Dose / conc.:

2 460 mg/m³ air

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

slightly swollen periocular tissue, and minimal perinasal and periocular encrustations in the 1000 ppm (2460 mg/m3) exposure concentration group

Key result

Dose descriptor:

NOAEC

Effect level:

ca. 1 230 mg/m³ air

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No studies were conducted on the target substance, titanium tetrapropanolate. As the target substance hydrolyses rapidly (half-life < 5 minutes) the intrinsic properties are related to hydrolysis products of the target substance, 1 -propanol.

Oral

In a limited repeated dose study, male rats were administered a nominal dose of 3000 mg/kg 1-proapnol for 4 months. Investigated parameters were restricted to body weight, food- and water consumption and alcohol uptake as well as liver weight and histology. Neither inflammation nor cirrhosis was seen in any of the livers. Thus, the dose of 3000 mg/kg bw/day is considered as NOAEL. (Hillbom et al. 1974)

 

Inhalation

Rats were exposed to 246, 1260 and 2460 mg/m3 for 6 hours/day 5 resp. 4 days/week up to 2 weeks (9 exposure days). No mortalities occur during this study. Exposure-related clinical observations were limited to slightly swollen periocular tissue, and minimal perinasal and periocular encrustations in the 1000 ppm exposure concentration group (Bushy Run 1992). A NOAEC of 500 ppm (1230 mg/m3) for irritative effects can be derived from limited studies described.

 

(cited from European Union Risk Assessment Report, propan-1-ol, 2008)

Dermal

There is no available studies on repeated dermal effects.

Justification for classification or non-classification

Based on the NOAEL (oral) and NOAEC (inhalation) 1 -propanol, there is no need for classification of the target substance in accordance with the criteria of CLP Regulation.