1,3,5-trioxane

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline with acceptable restrictions (no purity of test substance listed)

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Reference 2

Reference Type:

secondary source

Title:

1,3,5-TRIOXANE, CAS Number 110-88-3, USEPA HPV Challenge Program Submission

Author:

Trioxane Manufacturers Consortium Members, BASF Performance Copolymers, LLC (Formerly Ultraform Company) and Ticona

Year:

2000

Bibliographic source:

USEPA Submission

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

(adopted 1981)

GLP compliance:

yes

Remarks:

(Bio/dynamics Inc)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1,3,5-trioxane

EC Number:

203-812-5

EC Name:

1,3,5-trioxane

Cas Number:

110-88-3

Molecular formula:

C3H6O3

IUPAC Name:

1,3,5-trioxane

Details on test material:

- Name of test material (as cited in study report): Trioxane (C-235)
- Physical state: solid
- Lot/batch No.: 41115 AT
- Storage condition of test material: in a ventilated, temperature monitored room (15-29 °C)

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories
- Age at study initiation: males 9 weeks, females 12 weeks
- Mean weight at study initiation:
Group I - males 338 g (310 - 360) females 230 g (220 - 245);
Group II - males 329 g (315 - 342) females 226 g (219 - 239)
- Diet (e.g. ad libitum): Purina Rodent Laboratory Chow
- Water (e.g. ad libitum): automated watering system
- Acclimation period: 28-30 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure chamber volume: 100 L
- Source and rate of air: Chamber air was drawn through 1/4" Teflon line and regulated at a flow of 1 L/min for Group I or 0.5 L/min for Group II using a calibrated Dwyer flowmeter and Nupro metering valve. Chamber air was then directed to a glass "Y" tube where it was diluted with room air at a flow of 5 L/min. The resultant 5 to 1 chamber air dilution for Group I, or 10 to 1 chamber air dilution for Group II, was drawn into the Miran using a model Thomas 107CA 183 pump.
- Method of particle size determination: Particle size distribution samples were taken using a TSI Aerodynamic Particle Sizer equiped with a TSI Diluter.
- Temperature, humidity in air chamber: 24-27 °C, 40-48 %


TEST ATMOSPHERE
- Brief description of analytical method used: exposure levels were analysed using a Miran 1A Ambient Air Analyzer and a strip chart recorder.
- Samples taken from breathing zone: yes
- nominal cancentrations were determined by weighing.

TEST ATMOSPHERE
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 1.6/1.2 µm (exposure 1), 1.1/1 µm (exposure 2)

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

Initial dose: 8370 ppm, corresponding to 30.8 mg/l (measured).
Follow up dose: 10643 ppm, corresponding to 39.2 mg/l (measured), which was the maximum attainable vapour concentration.

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were observed individually, immediately prior to exposure, as a group at approximately 15-minute intervals during the first hour of exposure, and hourly thereafter. All animals were observed individually upon removal from the chamber (about one half-hour after exposure was completed) and at hours one and two post-exposure. Body weights were measured at day 1 (immediately prior to exposure), and on days 2, 3, 5, 8, and 15 (just prior to sacrifice).
- Necropsy of survivors performed: yes (including nasal passages, trachea, external surface, orifices, cranial cavity, carcass, brain, spinal chord, thoracic, abdominal and pelvic cavities and their viscera, cervical tissues and organs.
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 39.2 mg/L air

Exp. duration:

4 h

Remarks on result:

other: No mortalities observed at the highest tested dose of 39.2 mg/l air.

Mortality:

No mortalities were observed.

Clinical signs:

other: Increased secretory response, respiratory distress, and general signs of poor condition were reported.

Body weight:

There was a compound-related reduction in body weight for both sexes following exposure (8 - 9%). Animals gained body weight normally during the second week of the observation period.

Gross pathology:

At necropsy, no treatment-related abnormalities were observed, and no target organs could be identified.

Any other information on results incl. tables

Summary of symptoms

Test concentration	8370 ppm ( i.e. 30.8 mg/l air)
Symptom	Onset	Duration	Affected animals/treated animals
Lacrimation	4 h	14 days	Few
Shallow breathing	4 h	Less than 24 h	6/10
Irregular breathing	4 h	2 days	9/10
Reduced activity	45 min.	Less than 24 h	Most
Nasal discharge	4 h	14 days	About the half
	10643 ppm (i.e. 39.2 mg/l air)
Lacrimation	15 min.	13 days	Many
Shallow breathing	4 h	Less than 24 h	About the half
Irregular breathing	30 min.	5 days	All
Reduced activity	15 min.	Less than 24 h	All
Nasal discharge	4 h	14 days	Few to most

Summary of body weight data

Body weights (g)	Test concentration
	8370 ppm ( i.e. 30.8 mg/l air)
Time point (days)	0	2	3	5	8	15
Males	338	310	319	325	342	364
Females	230	210	218	221	233	239
	10643 ppm (i.e. 39.2 mg/l air)
Males	329	293	292	310	330	352
Females	226	210	216	216	224	235