Trimethyl orthoformate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1966

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

Study performed in 1966, probably no GLP, reasonably documented (2-page summary report). Only male animals investigated (6 per dose). Necropsy and histopathological evaluation, but shortened observation time (1-7 days) in lowest dose group. Submitted to US Office of Toxic Substances under TSCA, 1982.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1966

Report date:

1966

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Four-hour vapour inhalation, 5 dose groups of 6 male rats each. Time of death and symptoms recorded, weight development described, sacrifice and macro-/histopathology after 14 days (except lowest group).

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Trimethyl orthoformate

EC Number:

205-745-7

EC Name:

Trimethyl orthoformate

Cas Number:

149-73-5

Molecular formula:

C4H10O3

IUPAC Name:

trimethoxymethane

Details on test material:

- Name of test material (as cited in study report): Trimetyl orthoformate TMOF
- Substance type: pure active substance
- Physical state: liquid
- Analytical purity: 98%
- Vapour pressure: 50 mm Hg (6.67 kPa) at 30°C
- Boiling point: 100.6°C
- Impurities (identity and concentrations): no data
- Used as received

Test animals

Species:

rat

Strain:

other: ChR-CD

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 244-297 g
- Housing, diet, water, temperature, humidity etc.: no data

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: chamber containing 6 animals
- Exposure chamber volume: 16 L
- Method of holding animals in test chamber: not specified
- Source and rate, conditioning of air: no data
- System of generating vapour: Metering of test substance by syringe drive into T-tube heated to 120-140°C; stream of air carrying the vapour into the test chamber
- Method of particle size determination: not applicable to vapor (maximum concentration approximately 1/7 of saturation conc.)
- Treatment of exhaust air: not specified
- Temperature, humidity, pressure in air chamber: no data

TEST ATMOSPHERE
- Brief description of analytical method used: Hourly sampling of chamber atmosphere and determination of test substance by gas chromatography
- Samples taken from breathing zone: yes (assuming a homogeneous chamber atmosphere)

VEHICLE
- none

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: not applicable to vapor (approximately 1/7 of saturation concentration reached in chamber)

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gas chromatography

Duration of exposure:

4 h

Concentrations:

47.8, 44.0, 38.0, 36.2, 16.5 mg/L

No. of animals per sex per dose:

6 males

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days (except for lowest dose 16.5 mg/L: 2 rats each sacrificed at 1, 2, and 7 days post-exposure)
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology

Statistics:

Litchfield JT & Wilcoxon F (1949) J. Pharmacol. Exp. Therap. 96: 99-113

Results and discussion

Effect levels

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

> 40 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

Ranging from 6/6 at top dose to 0/6 at lowest dose. Death times: from 3 h 50 min (during the exposure) to 2 days post-exposure.
Sacrifice of survivors after 14 days (except lowest dose group, which had interim sacrifices of 2 animals each on days 1, 2, and 7).

Clinical signs:

other: During exposure: lacrimation, salivation, hyperpnea, dyspnea, hyperemia at all levels. Severe moist rales at lethal levels only. Unresponsiveness to slight responsiveness at lethal levels, mild responsiveness at non-lethal level. Post-exposure: Unresponsi

Body weight:

Normal weight gain after initial loss at lethal levels. Normal weight gain throughout at non-lethal level.

Gross pathology:

No gross pathalogical effects attributable to the test substance.

Other findings:

- Histopathology: pulmonary and hepatic congestions; other heaptic effects (not specified). Effects reversible: not found in survivors after 14 days, nor in interim sacrifices of the lowest dose group.
- Potential target organs: Lungs and liver; no findings in brain, spleen, bone marrow, testis, thymus, stomach, intestine, and skin.
- Other observations: Clinical signs and histologic findings indicate that trimethyl orthoformate is a respiratory irritant.

Any other information on results incl. tables

Mortaliy

Concentration (mg/L	Mortality ratio
47.8	6 / 6
44.0	5 / 6
38.0	2 / 6
36.2	1 / 6
16.2	0 / 6

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The substance does not meet GHS classification criteria for acute inhalation toxicity.