Dimethyl succinate

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:

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

Data source

Reference

Reference Type:

publication

Title:

Nasal lesion develpoment and reversibility in rats exposed to aerosols of dibasic esters

Author:

Lee K-P, Valentine R, Bogdanffy M S.

Year:

1992

Bibliographic source:

Toxicologic Pathology 20(3): 376-393, 1992

Materials and methods

Principles of method if other than guideline:

4 hour exposure to a single concentration. Groups of exposed aninals killed 1, 4, 7, 14, 21 and 42 days post-exposure for assessment of nasal lesions

GLP compliance:

not specified

Test type:

other: Assessment of nasal tolerance

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Dibasic esters

IUPAC Name:

Dibasic esters

Details on test material:

- Name of test material (as cited in study report): Dibasic esters
- Substance type: Mixture
- Physical state: Liquid
- Composition of test material, percentage of components: 66.0% dimethylglutarate; 16.5% dimethylsuccinate; 17.0% dimethyl adipate

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Raleigh, NC
- Age at study initiation: 7 weeks
- Housing: Indiviually caged
- Diet (e.g. ad libitum): Purina Rat Chow, ad-libitum except during exposure
- Water (e.g. ad libitum): Ad-libitum except during exposure
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 25 deg C
- Humidity (%): 40 - 60%
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 2 hours light / 12 hours dark

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

clean air

Mass median aerodynamic diameter (MMAD):

3.9 µm

Geometric standard deviation (GSD):

1.6

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure chamber volume: 150 L
- Method of holding animals in test chamber: Restraint tubes
- Source and rate of air: Ambient air, 20 L / minute
- Method of conditioning air: Filtration
- System of generating particulates/aerosols: Airlite H2500 Solo-Sphere Nebuliser
- Method of particle size determination: Sierra Series 210 cascade impactor with constant air flow sampling pump
- Treatment of exhaust air: Tandem dry ice cold traps and an MSA-activated charcoal/HEPA filter
- Temperature, humidity, pressure in air chamber: Temperature: 21.3 - 23.3 deg C; oxygen concentration: 20.4 - 20.9 %

TEST ATMOSPHERE
- Brief description of analytical method used: Gravimetrically from a glass fibre filter trap
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 3.9 micron / 1.6 micron

Duration of exposure:

4 h

Concentrations:

5900 mg / m3

No. of animals per sex per dose:

42 rats exposed, 7 killed 1, 4, 7, 14, 21 and 42 days post exposure

Control animals:

yes

Details on study design:

In an investiagtion of nasal tissue damage, morphogenesis and reversibility of lesions induced by dibasic esters, a mixture containing dimethyl succinate together with dimethyl adipate and dimethyl glutarate, male rats were exposed to a mixture concentration of 5900 mg/m3 (5.9 mg/L) for 4 hours. A control group of 24 rats were exposed to air only under the same conditions

Groups of 7 treated and 4 control animals were killed 1, 4, 7, 14, 21 and 42 days post-exposure and subjected to detailed microscopic examination of the nasal tissues.

Results and discussion

Effect levels

Sex:

male

Dose descriptor:

LC0

Effect level:

>= 5 900 mg/m³ air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

None

Applicant's summary and conclusion

Conclusions:

The tested substance, a mixture of dibasic esters containing 16.5% dimethylsuccinate, was not toxic at a concentration of 5900 mg / m3 following 4 hours inhalation exposure

Executive summary:

In an investigation of nasal tissue damage, morphogenesis and reversibility of lesions induced by dibasic esters, a mixture containing dimethyl succinate together with dimethyl adipate and dimethyl glutarate, male rats were exposed to a mixture concentration of 5900 mg/m3 (5.9 mg/L) for 4 hours. A control group of 24 rats were exposed to air only under the same conditions Groups of 7 treated and 4 control animals were killed 1, 4, 7, 14, 21 and 42 days post-exposure and subjected to detailed microscopic examination of the nasal tissues.

The tested substance, a mixture of dibasic esters containing 16.5% dimethylsuccinate, was not toxic at a concentration of 5900 mg / m3 (5.9 mg/L) following 4 hours inhalation exposure