Crotonaldehyde

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: Published Data

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1967

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

analytical

Principles of method if other than guideline:

Not applicable

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Crotonaldehyde

EC Number:

224-030-0

EC Name:

Crotonaldehyde

Cas Number:

4170-30-3

Molecular formula:

C4H6O

IUPAC Name:

but-2-enal

Details on test material:

90% purity
Eastman Organic Chemical P1878

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

120-150 g

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

None

Analytical verification of test atmosphere concentrations:

yes

Remarks:

colorimetric reaction of aldehydes with modified schiff-elvove reagent

Duration of exposure:

4 h

Concentrations:

50,60,70,100, 120, 240 ppm (analytical)
120, 110, 135, 175, 200, 390 ppm (nominal)

No. of animals per sex per dose:

10 animals per dose at 15, 30, 60, and 240 min exposures

Control animals:

yes

Details on study design:

animals were exposed to crotonaldhyde vapor for a period of 5 min to 4 hours at concentrations ranging rom 50 to 240 ppm.
Crotonaldehyde vapors were generated by bubbling dry nitrogen gas through the liquid crotonaldehyde. The saturated vapors were mixed with the appropriate amount of air to achieve the desired nominal concentration and passed into either a 20 liter glass chamber operating under positive pressure or (in the case of lower concentrations) a 1700 liter wooden chamber operating under negative pressure. Concentrations were varied by altering the nitrogen flow through the dispersion bubbler in order to volatilize varying amounts of crotonaldehyde per unit time or by varying the airflow through the chambers so as to change the dilution factor. In no case was the volume of added nitrogen more than 15% of the total flow, thereby maintaining an oxygen content of 17.8% or greater in the exposure vapor mixture. Dilutions of oxygen to this lower limit were made only in a very few exposures of five minutes duration, so the temporary decrease in oxygen content was not expected to have a physiological effect on the animals. After allowing sufficient time for the chambers to equilibrate, the animals were quickly introduced for the desired exposure period.

The method used for the studies reported herein is based on the colorimetric reaction of aldehydes with modified Schiff-Elvove reagent. Samples (two - five, depending on duration of exposure) of the chambers wre collected at intervals in aldehyde-free 1% methanol water. after dilution to an appropriate volume, Schiff Elvove reagent was added; the color was developed to a maximum for 60 to 75 minutes and read at a spectral wavelength of 888mu. it was found most desirable to run several standards with each batch of samples. It was also found that the samples could be kept stoppered for later analysis with no loss in anlytically determined quantities for up to 48 hours after sampling. Sample taken within a given exposure showed good agreement with a variability of no greater tha 5%; that is, for an average of 500ppm , samples would lie withint 475-525 ppm. On the other hand, analytical recoveries as a percentage of nominal concentration only averaged 42% and where quite variable 61% of theoretical. it is thought that absorption on chamber walls was largely responsible, although oxidation and polymerization are possible causes. No fixed pattern was observed that could be realted to concentration, airflow, chamber surface, etc.

Statistics:

The LC50 data were visually estimated from log-probit plots of the data at the indicated postexposure observation periods.

Results and discussion

Preliminary study:

not applicable

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LC50

Effect level:

120 ppm

Exp. duration:

4 h

Effect levels 2

Sex:

male

Dose descriptor:

LC50

Effect level:

600 ppm

Exp. duration:

1 h

Effect levels 3

Sex:

male

Dose descriptor:

LC50

Effect level:

800 ppm

Exp. duration:

30 min

Effect levels 4

Sex:

male

Dose descriptor:

LC50

Effect level:

1 300 ppm

Exp. duration:

15 min

Effect levels 5

Sex:

male

Dose descriptor:

LC50

Effect level:

1 820 ppm

Exp. duration:

10 min

Mortality:

see table in remarks

Clinical signs:

other: All animals exposed developed some signs of respiratory distress. Gasping was particularly prominent and was usually associated with a lower respiratory rate. Animals exposure to concentrations in excess of 1000 ppm also showed evidence of excitatory s

Body weight:

Weight losses in rats were quite pronounced following exposure, with survivors losing 10-25% of body weight by 24 hours post exposure, whereas nonexposed control animals gained on average 5% per day. The degree of weight loss was roughly proportional to the severity of the exposure as indicated by mortality. Recovery to pre-exposure weights required from 3 days to 2 weeks, again depending on the severity of the exposure. In several instances, the maximum weight loss did not occur until the second or third day after exposure. It was our experience that no animal died the was recovering toward its pre-exposure weight.

Gross pathology:

A few animals subjected to autopsy showed pulmonary congestion, but other organs appeared grossly normal.

Other findings:

none reported

Any other information on results incl. tables

Exposure Time (min)	Analytical average (ppm)	Time after exposure (days)
		1	2	3	4	7	14
0	0 0	0/5 0/6	0/5 0/6	0/5 0/6	0/5 0/6	0/5 0/6	0/5 0/6
5	1920 2420 2680 3180 4160 4640	0/5 0/5 0/5 3/5 4/5 4/5	0/5 0/5 1/5 3/5 4/5 5/5	0/5 0/5 1/5 3/5 4/5 5/5	0/5 0/5 1/5 3/5 4/5 5/5	0/5 0/5 1/5 3/5 4/5 5/5	0/5 1/5 1/5 3/5 4/5 5/5
10	800 1110 1380 1820 2050	0/12 0/12 3/12 6/12 8/12	0/12 0/12 4/12 7/12 8/12	0/12 0/12 4/12 7/12 9/12	0/12 0/12 4/12 7/12 9/12	1/12 1/12 4/12 7/12 9/12	1/12 4/12 6/12 7/12 9/12
15	550 680 750 850 980 1090 1290	0/10 0/10 2/10 2/10 3/10 3/10 5/10	0/10 2/10 4/10 3/10 6/10 5/10 7/10	0/10 2/10 4/10 5/10 6/10 7/10 9/10	0/10 2/10 4/10 5/10 6/10 7/10 10/10	0/10 2/10 4/10 5/10 7/10 8/10 10/10	0/10 2/10 5/10 7/10 7/10 8/10 10/10
30	370 420 530 675 800 890	0/10 1/10 2/10 4/10 5/10 6/10	0/10 2/10 4/10 6/10 7/10 9/10	0/10 2/10 4/10 6/10 7/10 9/10	0/10 2/10 4/10 6/10 7/10 9/10	0/10 2/10 4/10 6/10 7/10 9/10	0/10 2/10 4/10 6/10 8/10 9/10
60	1040 1090 910 1150 1450	1/10 3/10 3/10 4/10 8/10	1/10 4/10 5/10 6/10 9/10	1/10 4/10 5/10 7/10 10/10	2/10 5/10 6/10 7/10 10/10	3/10 5/10 6/10 7/10 10/10	4/10 6/10 7/10 7/10 10/10
240	50 60 70 100 120 200	0/10 0/10 0/10 4/10 5/10 6/10	0/10 0/10 1/10 5/10 5/10 6/10	1/10 0/10 1/10 5/10 6/10 7/10	1/10 2/10 3/10 5/10 8/10 9/10	1/10 2/10 3/10 5/10 8/10 9/10	1/10 2/10 4/10 6/10 8/10 9/10

 

Applicant's summary and conclusion

Interpretation of results:

toxic

Remarks:

Migrated information Criteria used for interpretation of results: US CPSC / US OSHA

Conclusions:

Toxic by inhalation based on 4 hour LC 50 in rats

Executive summary:

This study determined the LC50 values of crotonaldehyde vapor in Wistar rats. At exposure times of 15, 30, 60 and 240 minutes, 10 male animals per dose were exposed whole body in a chamber. The animals were observed for 14 days post exposure. LC50 value for for the 4 hour exposure was 120 ppm (336 mg/m3), nevertheless, a threshold level value ceiling of has been established at 0.3 ppm (0.86 mg/m3) to minimize the potential for rapid irritation to the respiratory tract and eyes.