Bis(2-ethylhexan-1-olato)bis(pentane-2,4-dionato-O,O')titanium

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Data waiving:

study technically not feasible

Justification for data waiving:

other:

Justification for type of information:

According to hydrolysis test results, the hydrolysis rate is estimated to be within several minutes. The hydrolysis products have been identified to be 2-ethylhexnol, acetylacetone and titanium dioxide. The acutoe toxicity of those organic parts have been well-investigated separately.

Reason / purpose for cross-reference:

data waiving: supporting information

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

2-ethylhexanol and pentane-2,4-dione are two main hydrolysis prodcuts of the target substance. Properties of the the two substance are used for read-across.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

not specified

Test type:

standard acute method

Species:

rat

Strain:

not specified

Sex:

not specified

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

330, 660 and 1320 mg/kg bw

No. of animals per sex per dose:

Not specified

Details on study design:

Substance was administered 5 days/week. Duration of observation:
Doage level 330 or 660 mg/kg bw /day : 17 days.
Dosage level 1320 mg/kg bw /day : 22 days.

Sex:

not specified

Dose descriptor:

LD50

Effect level:

ca. 3 290 mg/kg bw

Based on:

test mat.

95% CL:

2 870 - 3 790

Mortality:

2 rats died at the high dose leve.

Other findings:

Animals died in narcosis with no other findings.

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The oral LD50 on rats was 3290 mg/kg bw, and was classified as Category 5 according ly GHS criteria.

Executive summary:

As the target substance hydrolyses rapidly (half-life < 30 minutes) the intrinsic properties are related to hydrolysis products of the target substance. This information is used as a supporting evidence on the toxicity of the target substance in CSA.

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Justification for type of information:

2-ethylhexanol and pentane-2,4-dione are two main hydrolysis prodcuts of the target substance. Properties of the the two substance are used for read-across.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

not specified

Test type:

standard acute method

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

1, 0.71, 0.50, 0.25 ml/kg bw

No. of animals per sex per dose:

5

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

ca. 760 mg/kg bw

95% CL:

>= 655 - <= 890

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 570 mg/kg bw

95% CL:

>= 485 - <= 675

Clinical signs:

other: sluggishness, tremors, kyphosis, lacrimation, unsteady gait, comatose appearance and prostration.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

LD50 value tested on rat was 570 / 760 mg/kg bw in female/male. The substance was classified as category 4 according to GHS.

Executive summary:

As the target substance hydrolyses rapidly (half-life < 30 minutes) the intrinsic properties are related to hydrolysis products of the target substance. This information is used as a supporting evidence on the toxicity of the target substance in CSA.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 280 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: inhalation

Data waiving:

study technically not feasible

Justification for data waiving:

other:

Justification for type of information:

According to hydrolysis test results, the hydrolysis rate is estimated to be within several minutes. The hydrolysis products have been identified to be 2-ethylhexnol, acetylacetone and titanium dioxide. The [] of those organic parts have been well-investigated separately.

Reference 2

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

2-ethylhexanol and pentane-2,4-dione are two main hydrolysis prodcuts of the target substance. Properties of the the two substance are used for read-across.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

not specified

Test type:

traditional method

Species:

rat

Sex:

male/female

Route of administration:

inhalation: mixture of vapour and aerosol / mist

Type of inhalation exposure:

whole body

Vehicle:

air

Duration of exposure:

ca. 4 h

Concentrations:

5.3 mg/L (group I). 0.89 mg/L (group II)

No. of animals per sex per dose:

3

Details on study design:

Duration of observation period following administration: 7 days

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

>= 0.89 - <= 5.3 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

Group I (5.3 mg/L): all died.
Group II (0.89 mg/L) : none died.

Clinical signs:

other: Group I: One male and one female died during exposure after signs of respiratory distress, nasal discharge, chromodacryorrhea (blood tears), closed eyes and feebleness. Group II: all rats survived exposure and observation period with no notable effects.

Gross pathology:

Not carried out.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

LC50 value was between 0.89 and 5.3 mg/l. The substance was classified as category 4 according to GHS

Executive summary:

As the target substance hydrolyses rapidly (half-life < 30 minutes) the intrinsic properties are related to hydrolysis products of the target substance. This information is used as a supporting evidence on the toxicity of the target substance in CSA.

Reference 3

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Justification for type of information:

2-ethylhexanol and pentane-2,4-dione are two main hydrolysis prodcuts of the target substance. Properties of the the two substance are used for read-across.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

not specified

Test type:

traditional method

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Duration of exposure:

ca. 4 h

Concentrations:

628, 919, 1231, 1508 ppm

No. of animals per sex per dose:

10

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

ca. 1 224 ppm

Based on:

test mat.

Clinical signs:

other: Blepharospasm, lacrimation, abdominal breathing, urogenital wetness, decreased activity, encrustation around eyes and nose

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

4hr LC50 tested on rat was 1224 ppm (5.1 mg/l) and the subsatnce therefore was classified as catagory 3 according to GHS.

Executive summary:

As the target substance hydrolyses rapidly (half-life < 30 minutes) the intrinsic properties are related to hydrolysis products of the target substance. This information is used as a supporting evidence on the toxicity of the target substance in CSA.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

20 024 mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Data waiving:

study technically not feasible

Justification for data waiving:

other:

Justification for type of information:

According to hydrolysis test results, the hydrolysis rate is estimated to be within several minutes. The hydrolysis products have been identified to be 2-ethylhexnol, acetylacetone and titanium dioxide. The toxicity of those organic parts have been well-investigated separately.

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

2-ethylhexanol and pentane-2,4-dione are two main hydrolysis prodcuts of the target substance. Properties of the the two substance are used for read-across.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

not specified

Test type:

standard acute method

Species:

rabbit

Strain:

not specified

Sex:

not specified

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 2 600 mg/kg bw

Based on:

test mat.

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

LD50 value tested on rabbit was > 2600 mg/kg bw. 2 -ethylhexanol was therefore classified as Catagory 5 according to GHS.

Executive summary:

As the target substance hydrolyses rapidly (half-life < 30 minutes) the intrinsic properties are related to hydrolysis products of the target substance. This information is used as a supporting evidence on the toxicity of the target substance in CSA.

Reference 3

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Justification for type of information:

2-ethylhexanol and pentane-2,4-dione are two main hydrolysis prodcuts of the target substance. Properties of the the two substance are used for read-across.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

not specified

Test type:

standard acute method

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Duration of exposure:

24 hr

Doses:

0.5, 1, 2 ml/kg bw

No. of animals per sex per dose:

5

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 790 mg/kg bw

Based on:

test mat.

95% CL:

>= 560 - <= 980

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

ca. 1 370 mg/kg bw

Based on:

test mat.

95% CL:

>= 770 - <= 2 100

Mortality:

death occurred within 1-24 h after application

Clinical signs:

other: Red mottled lungs and congestion of the tracheal mucosa were observable. Local effects comprised erythema, edema, scab formation and necrosis.

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Acute dermal toxicity was tested using rabbit according to OECD guudeline 402. The LD50 values were 790 and 1370 for femal and male rabbits respectively. The lower value was chosen as the key result and the substance was classified as category 3 according to GHS.

Executive summary:

As the target substance hydrolyses rapidly (half-life < 30 minutes) the intrinsic properties are related to hydrolysis products of the target substance. This information is used as a supporting evidence on the toxicity of the target substance in CSA.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 160 mg/kg bw

Additional information

As the target substance hydrolyses rapidly (half-life < 30 minutes) the intrinsic properties are related to hydrolysis products of the target substance. This information is used as a supporting evidence on the toxicity of the target substance in CSA.

 

The acute toxicity of 2-ethylhexanol was investigated by the oral, dermal and inhalation route, respectively. The oral LD50 in rats was 3290 mg/kg bw (Schmidt P. et al., 1973, cited in BG-Chemie1995). The dermal LD50 was more than 2600 mg/kg bw in rabbits. Symptoms of acute intoxication were apathy, dyspnoea, cyanosis, loss of coordination, staggering and ataxia (Scala, RA., 1973, cited in BG-Chemie, 1995). The inhalation LC50 (4h) value in rats was between 0.89 and 5.3 mg/l. No signs of irritation, but the animals were hypoactive (Bio/Dynamics, 1989, cited in BG-Chemie 1995).

 

The acute toxicity of pentane-2,4-dione was investigated by the oral, dermal and inhalation route, respectively. By either route of administration the material proved to be moderately toxic to the animals tested. The oral LD50 in rats was 570 and 760 mg/kg bw, female and male respectively. The dermal LD50 in rabbits, applied to shaved skin, was 790 and 1370 mg/kg bw for female and male. The inhalation LC50 (4h) in Wistar rats was 1224 ppm, female and male. (Ballantyne B. et al., 1986)

 

TiO2 was considered non-hazardous, based on the published data on EHCA C&L database. The lowest dose reported to produce any toxic effect in rats by oral route is determined to be 60 g/kg (US EPA, 1994).

 

The most hazardous hydrolysis product – pentane-2,4-dione – was therefore used for CSA evaluation.

Justification for classification or non-classification

The oral LD50, inhalation LC50 and dermal LD50 read-across from pentane-2,4-dione are 570 mg/kg bw, 5006 mg/m3 and 790 mg/kg bw respectively.

 

As the intrinsic properties of the target substance are related to the decomposition products,the toxicity of the most hazardous hydrolysis product – pentane-2,4-dione – is used for assessing the toxicity of the target substance.Based on the fact that the target substance incorporated around 25 wt% pentane-2,4-dione as its raw material, the lethal doses are to be corrected by the factor 0.25. Corrected oral LD50, inhalation LC50 and dermal LD50 are 2280 mg/kg bw, 20024 mg/m3 and 3160 mg/kg bw respectively.

 

The target substance is not classified according to CLP Regulation 1272/2008.