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Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No GLP, short documentation, comparable to OECD TG 403

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report date:
1981

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Principles of method if other than guideline:
Similar to OECD TG 403. Two independent experiments were performed with 7.7  and 5.4 mg/l adipic acid, with 20 animals per concentration.  Head/nose-only exposure was the technique used (system INA 20, BASF;  animals were sitting in tubes and the mouth protruded into the inhalation  chamber). It is unclear whether the eyes of the animals were exposed  also.  A dust atmosphere with a particle-size mass distribution (MMAD50) of 3.5  µm (i.e. 50% of the particles had a MMAD < 3.5 µm) and a geometric  standard deviation (GSD) of 2.6 was used throughout the experiment. The  maximal attainable concentration in this test was 7.7 mg/l. Animals were exposed for 4 hours. Body weights and general appearance were recorded daily throughout the experimental period. After 14 days animals were killed and gross autopsy was performed.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Adipic acid
EC Number:
204-673-3
EC Name:
Adipic acid
Cas Number:
124-04-9
Molecular formula:
C6H10O4
IUPAC Name:
Hexanedioic acid
Test material form:
not specified
Details on test material:
- Name of test material (as cited in study report): adipic acid
- Purity: 99.8%
- Appearance: white powder, particle size < 25 µm
- Stability under test conditions: at least 2 years

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: WIGA, Sulzfeld, Germany
- Age at study initiation: 6 - 8 weeks
- Weight at study initiation: 185 + / - 15 g
- Housing: five animals per cage type D III, Becker, Germany
- Diet: Herilan MRH (Eggersmann KG, Riteln/Weser, Germany), ad libitum
- Water: tap water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2 °C
- Humidity (%): 55 +/- 5 %
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
other: dust/aerosol
Type of inhalation exposure:
nose/head only
Vehicle:
other: no vehicle
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Head - Nose - inhalation system INA 20, BASF
- Exposure chamber volume: 60 l
- Generation of test atmosphere: A dust/aerosol was generated by a dust generator and fed to the inhalation system. The concentration was adjusted by changes of the width of the gap and variations of the vibration amplitude of the dosing device. The air was adjusted to 500l/h compressed air through the injector and 500 l/h blowing air for dilution.
- Method of particle size determination: At earliest 30 min after the start of the experiment, one sample was taken. Prior to sampling the impactor was fitted with a collection disc and a residue particle filter. The impactor was connected to the pump and the apparatus and one sample (9 l) was taken. Therefore the collection disc and the residue particle filter were weight and the content of the preimpactor determined by gravimetry.

TEST ATMOSPHERE
- Analytical method used: gravimetric determination of the concentration
- Samples taken from breathing zone: yes, every half hour one sample per concentration group

TEST ATMOSPHERE
- MMAD (Mass median aerodynamic diameter): 3.5 µm / GSD (Geometric st. dev.): 2.6
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
7.67 mg/l analytical concentration (nominal concentration 43.8 mg/l)
5.41 mg/l analytical concentration (nominal concentration 29.88 mg/l)
No. of animals per sex per dose:
10
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: clinical symptoms and mortality was observed on a daily basis
- Frequency of weighing: prior to the experiment, after one week and at the end of the observation period
- Necropsy of survivors performed: yes
Statistics:
- The concentration-effect-relation was calculated following the binominal test (Wittig, H.: Mathematische Statistik 1974, p 32-35)
- The particle size determination followed the mathematical and graphical analysis for particle size determination (Silverman, L.: Particle Size Analysis in Industrial Hygiene, 1971, p. 235-259)

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC0
Effect level:
> 7.7 mg/L air
Exp. duration:
4 h
Remarks on result:
other: no mortalities observed
Mortality:
No mortalities observed
Clinical signs:
other: Nothing abnormal observed
Body weight:
Constant body weight gain of 25 - 40 g during the 14 days observation period.
Gross pathology:
Nothing abnormal observed

Any other information on results incl. tables

Neither mortality nor symptoms were observed during and after exposure.  

No pathological changes were reported at necropsy.

Applicant's summary and conclusion

Executive summary:

In a study similar to OECD TG 403, neither mortality, toxic symptoms nor macroscopic pathological changes were observed in 20 rats exposed for 4 hours (nose/head only) to the maximal attainable concentration of 7700 mg/m3 of adipic acid (99.8 %) dust. 50 % of the particles had a MMAD below 3.5 µm.