Tetra-n-butyl titanate, polymer with water

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

Study period:

1993

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study intended to determine co-exposure effect of xylene and n-butyl alcohol, rotarod performance and respiratory depression measured according to standard protocol but guideline followed was not mention. 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 alcohol and hydrated titanium dioxide. This rapid hydrolysis (hydrolysis half-life < 3 minutes to < 2 hours) 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 hazardous degradation product (alcohol) released from the target substance. The identification of degradation products from the hydrolysis study conducted for the target substance verifies that there are no impurities in the alcohol released from the target substance, which might change the hazardous properties of the target substance compared to the properties of the pure alcohol. As there is a mechanistic reasoning to the read-across, the unnecessary animal testing is avoided by using the read-across data from the degradation product (relevant alcohol) to evaluate irritation, sensitization and the short term and long-term toxicological effects and mutagenicity of the target substance.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1993

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Rotarod performance was tested according to the principle described by Kaplan and Murphy.

GLP compliance:

not specified

Test type:

other:

Test material

Test material information

Constituent 1

Constituent 2

Reference substance name:

Butan-1-ol

EC Number:

200-751-6

EC Name:

Butan-1-ol

Cas Number:

71-36-3

Molecular formula:

C4H10O

IUPAC Name:

1-Butanol

Test material form:

other: vapours, generated by heating liquid solvent

Details on test material:

- Name of test material: :n-butyl alcohol
- Substance type solvent
- Physical state: vapours, generated by heating liquid

Test animals

Species:

other: Rats and mice

Strain:

other: Wistar rats and balb/c mice

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: DAK Stock outbred
- Weight at study initiation: 250-300g for rats and 25-30 g mice

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

other:

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Dynamic inhalation chamber
- Exposure chamber volume: 1.3 M^3


TEST ATMOSPHERE
- Brief description of analytical method used: The concentration of solvent vapours were measured every 30 min with a gas chromatograph with flame ionization detector using 1.5 m metal column with 10% OV -17 on chromosorb WHP (80-100 mesh) as a stationary phase at column temprature of 100 C.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Gas chromatography

Duration of exposure:

4 h

Remarks on duration:

4hr exposure period was for rats and mice exposed for 6 min as to determine respiratory depression.

Concentrations:

Exposure concentration of n-butyl alcohol were expressed in ppm and 1 ppm of n-butyl alcohal = 3.08 mg/m3. and for n- butyl alcohol exposed concentration range was 100 to 100000 ppm.

No. of animals per sex per dose:

8-10 male mice per group for measuring respiratory rate
10 male rats per group for measuring rotarod performance

Control animals:

yes

Details on study design:

- Duration of observation period following administration: no data

- Other examinations performed: Rotarod performance was tested before exposure and immediately after exposure to several concentration of n-butyl alcohol and in control animal for 1 hour.

The respiratory pattern was recorded continuously before the exposure solvents, during 6 min of exposure and 6 min after termination of exposure.
Spontaneous motor activity was measured by the use of UMA-2-10 actometer during one hour immediately after termination of 4 hour exposure to rats

Statistics:

Probit analysis was applied to determin the medial effective concentration (EC50 and RD50 value). Frequency data were also compared using the Chi-square test.

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

other: EC 50

Effect level:

6 531 ppm

Based on:

other: rotarod performance

95% CL:

4 950 - 10 370

Exp. duration:

4 h

Effect levels 2

Sex:

male

Dose descriptor:

other: RD50: concentration dependent decrease in respiratory rate to 50%

Effect level:

3 008 ppm

Based on:

other: plethysmographic method

Mortality:

no data

Clinical signs:

other: 1) Depression of central nervous system 2) irritation of eyes and upper respiratory tract

Body weight:

no data

Gross pathology:

no data

Other findings:

- Potential target organs: Central nervous system

Any other information on results incl. tables

All rats exposued for 4 hours to the tested concentrations of n-butyl alcohol and mixture survived the exposure, both solvents and thair mixture caused concentration dependent disturbances in rotarod performance of rats (refer the attached background material).

Both m-xylene and n-butyl alcohol caused a concentration dependent decrease in respiratory rate in mice (refer the attached background materia).

N-butyl alcohol and mixture solvents changed the spontaneous motor activity in the rat (refer the attached background materia).

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

In this study neurotoxicity of n-butanol assessed on the basis of rotarod performance and spontaneous motor activity and the irritation effect was quantified by measurement of respiratory rate in mice. For n-butanol EC50 ( medial effective concentration) and RD50 (concentration dependent decrease in respiratory rate to 50%) were determined as 6531 ppm and 3008 ppm respectively.

Executive summary:

As the target substance hydrolyses immediately (half-life <2 hours) the intrinsic properties are related to this main organic degradation product (butanol) of the target substance. This information is used as a weight of evidence in CSA.