Diethoxymethane

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

February 17-November 11, 1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to OECD guideline 403 and following GLP principles

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Test material

Test material information

Constituent 1

Reference substance name:

Diethoxymethane

EC Number:

207-330-6

EC Name:

Diethoxymethane

Cas Number:

462-95-3

Molecular formula:

C5H12O2

IUPAC Name:

diethoxymethane

Details on test material:

- Name of test material (as cited in study report): diethoxymethane
- Analytical purity: 99.9%
- Impurities (identity and concentrations): pyrogallol (10 ppm)
- Lot/batch No.: X-19085-9

Test animals

Species:

rat

Strain:

other: CRL:CD(SD)BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, MA
- Age at study initiation:
- Weight at study initiation: 212-250 g (males) and 192-224 g (females)
- Fasting period before study:
- Housing: Animals were singly housed in multicompartmented stainless steel mesh cages
- Diet (e.g. ad libitum): Certified feed (Agway Prolab Animal Diet (RMH 3000, pellets)) available ad lib
- Water (e.g. ad libitum): Water (Monroe County Water Authority) ad lib
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 36-43
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

clean air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
Exposures were conducted in 20 L glass bell jar inhalation chambers contained in a hood. Chambers were maintained under slight positive pressure and at 15-20 air changes per hour. Atmospheres were produced by passing metered dried oil-free compressed air over the surface of the test material contained in a 500 ml round bottom flask. Controls were treated identically to the test groups, except that exposure was to filtered air only. Temperature was determined hourly and nominal chamber concentration for the exposure was calculated.

TEST ATMOSPHERE
- Brief description of analytical method used: Chamber vapor concentrations were determined at least once per hour by a Miran IA infrared analyser equipped for automated sampling and analysis. On the morning and afternoon of the exposure, concentration of background nongaseous material was measured in the high concentration (20000 ppm) chamber relative to the control chamber in order to insure that exposure were to vapor and not aerosol.
- Samples taken from breathing zone: yes

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

6 h

Concentrations:

0, 5000, 10000 and 20000 ppm

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: before and after exposure and twice daily thereafter for observations; on days 0, 3, 7, 10, 14 and at necropsy for body weight
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology

Statistics:

One-way analysis of variance (ANOVA), Bartlett's test and Duncan's multiple range test using a P value ≤ 0.05 to indicate statistical significance. LC50 and its 95% CL were estimated by probit analysis using SAS Institute Inc. Version 5, 1985 (Cary, NC)

Results and discussion

Preliminary study:

Not relevant

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

6 643 ppm

Based on:

test mat.

95% CL:

5 117 - 8 476

Exp. duration:

6 h

Mortality:

Males: death of 5/5 at 20000 ppm (within 3 hours into exposure); death of 5/5 at 10000 ppm (during the 6-hour exposure); no death at 5000 ppm.
Females: death of 5/5 at 20000 ppm (within 5 hours into exposure); death of 4/5 at 10000 ppm (during the 6-hour exposure); death of 2/5 at 5000 ppm (shortly after exposure).

Clinical signs:

other: During exposure: wobbly gait, lethargy and narcosis. Following exposure: For males: lethargy and gait disturbance at 5000 ppm. Corneal opacy for 1/5 on Day 7 to the end. For females: lethargy at 5000 ppm; narcosis following exposure at 10000 ppm All the

Body weight:

BW gain of all the surviving animals was comparable to control values.

Gross pathology:

Treatment-related changes were observed in the lungs and livers of all 3 exposure groups in females and the high- and middle-exposure groups of males. They were characterized as the incomplete collapse of lungs on thoratomy and enlarged livers. Failure of the lungs to collapse upon thoracotomy was probably caused by edema. The cause of the enlarged livers was not determined. Tissues were not collected for microscopic evaluation.
Inflammatory eye changes were observed in 4 female rats from the high dose group. Microscopic evaluation of the affected eyes revealed unilateral or bilateral congestion and edema of the ciliary body and hemorrhage of the choroid.

Other findings:

Aerosol measurements:
Measurements obtained with the Roco Model 225 Aerosol Particle Conter (HIAC/Royco Instruments Division, Pacific Scientific, Menlo Park, CA) revealed that an aerosol was not present.

Any other information on results incl. tables

Nominal concentrations differed from the analytical ones:

Concentration	Low (ppm)	Intermediate (ppm)	High (ppm)
Nominal	5000	10000	20000
Analytical (males)	5357 ± 413	9802 ± 814	20029 ± 219
Analytical (females)	5060 ± 181	9393 ± 840	16802 ± 4054

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The 6-hour LC50 value for males and females rats combined is 6643 ppm with a 95% confidence interval of 5117 to 8476 ppm in the acute inhalation toxicity study of diethoxymethane.

Executive summary:

An acute inhalation toxicity test was performed in the rat according to OECD guideline 401 and GLP compliance.

Groups of 5 male and 5 female rats were exposed to target vapor concentrations of 20000, 10000, 5000 or 0 ppm diethoxymethane (DEM) for 6 hours and then held for 14 days of observation. DEm caused lethargy, gait disturbance, narcosis and death in all rats, within 5 hours during exposure to 20000 ppm, and by 6 hours in all but one rat exposed to 10000 ppm. All the males and females survived exposure to 5000 ppm but 2 females died shorthly thereafter. Treatment-related gross changes in animals dying spontaneously were incomplete collapse of lungs and enlarged livers. No microscopic examinations were conducted. Other than transient narcosis, lethargy or gait disturbance following exposure, there were no compound-related clinical signs of toxicity or changes in bw gain in females which survived exposure to 5000 ppm. No treatment-related gross changes were seen in the surviving female exposed to 10000 ppm or in males exposed to 5000 ppm. Incomplete collapse of the lungs and enlarged livers were seen in females surviving exposure to 5000 ppm. Except for the microscopic examination of eyes which showed incidental inflammatory changes in 4 females exposed to 20000 ppm, no other microscopic examonations were performed. The lung and liver are sites of toxicity at these high concentrations. A no-effect level of toxicity was not determined.

The 6-hour LC50 value for males and females rats combined is 6643 ppm with a 95% confidence interval of 5117 to 8476 ppm in the acute inhalation toxicity study of DEM.