Isopropylamine

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1150 (Acute inhalation toxicity)

GLP compliance:

yes

Test type:

standard acute method

Test material

Test material information

Constituent 1

Reference substance name:

Isopropylamine

EC Number:

200-860-9

EC Name:

Isopropylamine

Cas Number:

75-31-0

Molecular formula:

C3H9N

IUPAC Name:

propan-2-amine

Test material form:

liquid

Details on test material:

Isopropylamine [CAS No. 75-31-0]; supplied by Hoechst Celanese Corp. (C-899; 100% active ingredient)
purity > 99%, for further details, please see statement on test material purity for older studies on isopropylamine, attached in IUCLID section 13.

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, Inc., Raleigh, North Carolina, USA
- Age at study initiation: males 8 - 9 wk, females 10 - 11 wk
- Weight at study initiation: males: 242 g - 335g, females: 208g - 236g
- Housing: doubly housed during acclimation period, individually housed in Plexiglass chamber (100 L) during exposure
- Diet , water: ad libitum
- Acclimation period: 1 to 3 wk

ENVIRONMENTAL CONDITIONS during acclimation period
- Temperature (°C): 19 - 24°C
- Humidity (%): 40 - 70%
- Air changes (per hr): no data
- Photoperiod: 12hrs dark / 12hrs light)

ENVIRONMENTAL CONDITIONS during exposure
- Temperature (°C): 21 - 26°C
- Humidity (%): 46 - 65%
- Air flow rate: 20 L/min (= complete air change every 5 min)

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 apparatus: Plexiglass exposure chamber with glass front
- Exposure chamber volume: 100 L
- Method of holding animals in test chamber: individually
- Source and rate of air: 20 L/min, the air exchange was about once per every 5 min.
- Method of conditioning air: by passing air through a midget impinger containing the TS
- System of generating particulates/aerosols:
- Temperature: actual 21-26°C
- Relative humidity: 64-65%
- pressure: no information given

TEST ATMOSPHERE
- Brief description of analytical method used: MIRAN Ambient Air Analyser; test atmosphere was drawn through Balston DFU filter via Teflon line into the Analyser
- Samples taken from breathing zone: yes (hourly sampling)

- Particle size measurements were performed at hourly intervals

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

5.3, 2.8, 5.1, and 6.5 mg/L (analytical) [7.1, 3.4, 5.9, and 7.2 mg/L (nominal)], no aerosol

The nominal concentration was calculated from the consumption of TS from the reservoir divided by the total amount of air.

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days; detailed observations once daily for survivers; Assessment of viability twice daily
- Necropsy of survivors performed: yes (at post-exposure day 15)
- Examinations of dead and surviving animals of nasal passages, trachea, orifices, cranial cavity, brain and spinal cord, viscera, cervical tissues and organs

Statistics:

Calculation of median lethal concentration, 95% CL (method according to Litchfield and Wilcoxon)

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

ca. 8.7 mg/L air (analytical)

95% CL:

>= 6.5 - <= 12

Exp. duration:

4 h

Effect levels 2

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

ca. 3 540 ppm

Exp. duration:

4 h

Remarks on result:

other: calculated from formula 1 ppm = 2.46mg/m^3

Effect levels 3

Key result

Sex:

female

Dose descriptor:

LC50

Effect level:

7.7 mg/L air (analytical)

Exp. duration:

4 h

Effect levels 4

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

ca. 9.4 mg/L air (analytical)

Exp. duration:

4 h

Mortality:

see table below

Clinical signs:

other: Labored breathing, lacrimation, nasal discharge, reduced activity, closed eyes. Respiratory distress and nasal discharge persisted the first week of post-exposure, but moist and dry rales were observed in most of the survivors throughout 14 d.

Body weight:

Transient losses were prominent.

Gross pathology:

Nasal tubinates and lungs were reddened and swollen with lung emphysema present in a few animals.

Any other information on results incl. tables

Group   Mean Exposure  Nominal [mg/L]        Mortality
  
    
    
    
    
    
    
    
    

tration   Concentration     No.dead/No.exposed























----------------------------------------------------------------
I*         5.3             7.1           5/5    2/5     7/10           
II         2.8             3.4           0/5    0/5     0/10
III        5.1             5.9           2/5    0/5     2/10
IV         6.5             7.2           1/5    2/5     3/10
 ================================================================
* Group I was excluded from evaluation due to technical problems 
  during exposure

The LD50 of 8.7 mg/L (95% C.I. = 6.5 - 12 mg/L) is the combined 
extrapolated value.  
 -----------------

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Under the conditions of this study, the mean LC50 in male and female rats was 8.7 mg/L (8700 mg/m3)

Executive summary:

The study was designed to assess the acute inhalation toxicity (median lethal concentration). Groups of 5 rats per sex were exposed to 5.3, 2.8, 5.1, and 6.5 mg/L (analytical) [7.1, 3.4, 5.9, and 7.2 mg/L (nominal)] of test substance vapour for 4 h. The post-exposure observation period was 14 days. The LC50 for combined sexes was 8.7 mg/L. Clinical signs during exposure were laboured breathing, lacrimation, nasal discharge, reduced  activity, closed eyes. Respiratory distress and nasal discharge persisted  the first week of post-exposure, but moist and dry rales were observed in  most of the survivors  throughout 14 d. Significant body weight losses were evident following exposure, but recovery occured over time. No clear treatment-related postmortem findings were observed.