Bis(ethyl acetoacetato-O1',O3)bis(2-methylpropan-1-olato)titanium

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Data obtained from an authoritative secondary source. Read-across justification: The substance is hydrolytically unstable. When it comes in contact with water or moisture complete hydrolysis will take place with no significant reaction products other than alcohols, ethyl acetoacetate and hydrated titanium dioxide. The half-life of hydrolysis is < 10 minutes @ 25 ˚C. This rapid hydrolysis is the driving force for the toxicokinetics of target substance. Because of the rapid hydrolysis, the influence of the mode of administration through inhalation, dermal and oral is related to the most hazardous degradation products released from the target substance. In addition, because of rapid hydrolysis the dermal effects of the target substance are similar to the irritating properties of the degradation products. The identification of degradation products from the hydrolysis study conducted for the target substance verifies that there are no impurities in the mixture of particular alcohol and ethyl acetoacetate which might change the hazardous properties of the target substance compared to the properties of the pure alcohol and ethyl acetoacetate. As there is a mechanistic reasoning to the read-across, the unnecessary animal testing is avoided by using the read-across from the most hazardous degradation products (alcohols) to evaluate irritation, sensitization and the short-term and long-term toxicological effects of the target substance.

Data source

Reference

Reference Type:

secondary source

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Male and females rats (10/sex/concentration) were exposed to isobutanol for 6 hours, immediately followed by a motor activity determination and a
functional observational battery (FOB).

GLP compliance:

yes

Remarks:

No testing laboratory specified in the publication

Test material

Test material information

Constituent 1

Reference substance name:

2-methylpropan-1-ol

EC Number:

201-148-0

EC Name:

2-methylpropan-1-ol

Cas Number:

78-83-1

Molecular formula:

C4H10O

IUPAC Name:

2-methylpropan-1-ol

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

not specified

Duration of exposure:

6 h

Concentrations:

0, 1500, 3000, and 6000 ppm (0, 4545, 9090, 18180 mg/m3)

No. of animals per sex per dose:

10/sex/concentration

Control animals:

yes

Details on study design:

All of the rats on study were
subdivided into four FOB assessment groups and exposed (and data
collected) on different days in order to obtain timelier FOB assessments.
Body weight data was collected on Day 1 (pre-exposure), 7, and 14. During
exposure assessments were limited to a crude startle response reflex
determination for the animals visible thru the exposure chamber windows.
The stimulus startle response was initiated by sharply striking an object
against the stainless steel exterior wall of the chamber. Post-exposure motor
activity (60 minutes) and FOB tests were conducted pre-test (1-2 weeks
prior to exposure), immediately following exposure (Day 1) and seven and
fourteen days after the exposure. An additional motor activity test was
conducted on Day 2. FOB assessments were conducted approximately 10-
30 minutes after the motor activity test ended. An automated apparatus was
used to conduct motor activity tests while trained observers blind to the test
status of the animals conducted the FOB tests.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

18 180 mg/m³ air

Remarks on result:

other: no mortality was observed at the highest concentration tested (18180 mg/m3)

Mortality:

no mortalities were observed

Other findings:

No exposure related differences were noted between the control and exposed groups. Hypoactivity and diminished response to a startle reflex was observed during exposure for the 3000 ppm (9090 mg/m3) and 6000 ppm (18180 mg/m3) exposures. Decreases in motor activity were noted post-exposure in the 6000 ppm (18180 mg/m3) group but not the 3000 ppm (9090 mg/m3) or 1500 ppm 4545 mg/m3) groups. No effect on motor activity was detected at the 7 and 14 day time points. No exposure-related effects were noted in the FOB
assessment.

Any other information on results incl. tables

Read-across justifications and data matrices are presented in IUCLID section 13.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

Male and female rats exposed to atmospheric vapor levels of 0, 1500, 3000, or 6000 ppm (0, 4550, 9090, 18180 mg/m3) for six hours were evaluated in a neurobehavioral battery. No mortality was observed in any exposure groups. Thus, the LC50 value was concluded to be > 18180 mg/m3.

Executive summary:

The exposed rats were evaluated in a neurobehavioral battery (motor activity determination and a functional observational battery) within two hours post-exposure. Hypoactivity and diminished response to a startle reflex (during the inhalation exposure) was observed during exposure for the 3000 and 6000 ppm (9090 and 18180 mg/m3) exposures. Decreases in motor activity were noted post-exposure in the 6000 ppm (18180 mg/m3 ) groups but not the 3000 or 1500 ppm (9090 or 4550 mg/m3 )groups. No effect on motor activity was detected at the 7 and 14 -day time points. No exposure-related effects were noted in the FOB assessment. Since no mortality was observed at the highest concentration level tested, the LC50 value is determined to be > 18180 mg/m3.