3-chloropropene

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1977-05-24 - 1982-06-04

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: - scientifically sound study, non GLP - animals necropsied after 3 to 7 d

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1982

Report date:

1982

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

: animals were sacrificed and necropsied after 3-7 d post treatment, histologic examinations were carried out

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3-chloropropene

EC Number:

203-457-6

EC Name:

3-chloropropene

Cas Number:

107-05-1

Molecular formula:

C3H5Cl

IUPAC Name:

3-chloroprop-1-ene

Details on test material:

- Name of test material (as cited in study report): allyl chloride
CHARGE I
- Substance type: chlorinated short-chain hydrocarbon
- Physical state: liquid, color: 0-5 ALPHA
- Analytical purity: 99.8 % (w/w)
- Impurities (identity and concentrations): in % (w/w)
2-Chloropropene 0.01
Isoprophyl Chloride 0.57
1,5-Hexadiene 0.28
Normal Propyl Chloride 0.19
Acetonitrile 0.03
3,3-Dichloropropene 0.04
Propylene Chloride 0.03
the sum of all ingredients is > 100 %
- Purity test date: not reported
- Lot/batch No.: 01047-1
- Supplier: The DOW Chemical Company, Freeport, Texas
- Stability under test conditions: not reported, but expected to be stable
- Storage condition of test material: not reported
CHARGE II
In addition, a single 1000 ppm exposure study was cIn addition, a single 1000 ppm exposure study was conducted with water-washed allyl chloride, representative of production-grade material obtained from the Shell Chemical Company, Houston, Texas. Although an analysis was not provided for the Shell Chemical Company sample, vapor-phase infrared spectrophotometric analysis was performed on the Shell sample and on the sample produced by The Dow Chemical Company and the spectra obtained were compared with a reference spectrum from the Aldrich Chemical Company (The Aldrich Library of Infrared Spectra, p. 50F). All spectra were identical in all essential details (Hermann, E.A., Analytical Data Sheet No. IT-7-77, Toxicology Research Laboratory, Dow Chemical U.S.A., 1977).

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories, Wilmington, Massachusetts, U.S.A.
- Age at study initiation: 9-14 wks
- Weight at study initiation: males: 192 - 284 g (average values of different doses on day 0); females: 130 - 166 g (average values of different doses on day 0)
- Fasting period before study: no, food and drink withheld during exposure
- Housing: Upon arrival in the laboratory, rats were housed 5/cage, Immediately prior to each exposure, animals were placed in stainless steel exposure cages in groups of either 5 or 10/cage, after exposure, they were placed in their original holding cages in an animal room which was used to house the control groups, until the time of necropsy
- Diet (e.g. ad libitum): Food (Purina Rat Chow), ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: > 7 d


ENVIRONMENTAL CONDITIONS
not reported

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: glass and stainless steel chambe
- Exposure chamber volume: 160-liter
- Method of holding animals in test chamber: animals were placed in stainless steel exposure cages in groups of either 5 or 10/cage
- Source and rate of air: not reported
- Method of conditioning air: metering a calculated amount of allyl chloride liquid into a heated (approximately 80°C) vaporization flask with a precision syringe pump and sweeping the vapor with filtered air into the main chamber airflow at a rate of approximately 30 liters/minute
- Method of particle size determination: not applicable, vapors of a volatile organic substance
- Treatment of exhaust air: not reported
- Temperature, humidity, pressure in air chamber: not reported


TEST ATMOSPHERE
- Brief description of analytical method used:
online monitoring: IR
a Wilks-Miran IA-CVF infrared spectrophotometer was used to determine analytical concentration for the 500, 800, 1200, 2000, and two remaining 1000 ppm exposures.
timed measurements: GC-FID
For the 200 and 300 ppm allyl chloride exposures, and for the initial 1000 ppm allyl chloride exposure, the analytical concentration of allyl chloride in the chamber was determined using a Varian Aerograph Series 2400 gas chromatograph equipped with 1 ml gas sampling loops and a flame ionization detector. A Varian A-25 recorder was used to monitor the G.C. output. Gas chromatographic conditions were as follows:
Column: 10% UCW on 80/100 mesh Chromosorb W
Temperatures: Column 58°C
Detector 188°C
Gas Flow Rates: Air 300 ml/min
Hydrogen 60 ml/min
Nitrogen 60 ml/min
- Samples taken from breathing zone: not reported

Analytical verification of test atmosphere concentrations:

yes

Remarks:

online monitoring: IR, timed measurements: GC-FID

Duration of exposure:

6 h

Concentrations:

200, 300, 500, 800, 1000 and 2000 ppm

No. of animals per sex per dose:

10

Control animals:

other: yes, controls for each group (see table 1 for details)

Details on study design:

- Duration of observation period following administration:
see table 1
- Frequency of observations and weighing: pre exposure (day 0), 24 h post exposure (day 1), 48 h post exposure (day 2, 2000 ppm, males only), 72 h post exposure (day 3, 500 and 800 ppm only, both sexes)
- Necropsy of survivors performed: yes
- Other examinations performed:
clinical signs: yes
body weight: yes
organ weights: liver and kidneys
clinical chemistry: BUN, SGPT, AP, SGOT and glucose
histopathology: liver and kidney samples

Statistics:

Body weight, clinical chemistry and organ weight data were analyzed statistically using Dunnett's test. The level of significance for all cases was p<0.05.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

other: LC50: not determinable as rats were sacrificed at day 3 to 7

Effect level:

0 ppm

Mortality:

- mortality is only tracked until day 3 as in most dose groups animals have been sacrificed at this day
- for details see table 2

Clinical signs:

other: - < 2000 ppm: recovery from the exposure-related in-life findings occurred in all groups by 18 to 72 hours post exposure - 2000 ppm: female rats: all died within the first 24 hours post exposure without evidence of recovering from the in-life observation

Body weight:

- 24 h: rats in all exposed groups experienced a loss of body weight; the percent lost increased with increasing exposure concentration.
In general, the female rats experienced a greater weight loss than did the males during this time interval.
- 48h: 2000 ppm males only, weights are clearly down
-72 h: 500 and 800 ppm only: weights show a tendency for recovery for animals of these dose groups
- see table 4 for details

Gross pathology:

- nasal turbinate: both 1000 ppm groups: nasal discharge
2000 ppm: hyperemic and/or edematous
- liver: accentuated lobular pattern with or without associated pale appearance at 1000 and 2000 ppm
- kidneys: pale discoloration of cortex at 300 ppm and 500 ppm, pale cortex with darker medullary junction and generally enlarged or swollen kidneys at 800 ppm and higher
- thymus: decreased in size at 1000 ppm and higher
- gastrointestinal tract - decreased contents and depletion of abdominal adipose tissue at 1000 ppm and higher
- testes: edematous at 1000 ppm

Other findings:

-clinical biochemistry: for biochemical parameters only the BUN concentration shows a clear dose dependent effects (rise) becoming statistically significant at 1000 ppm in males and at 500 ppm in females at 24 h post exposure. 72 h post exposure at some of the higher dose groups a reduction in AP activity was found but no clear trend was obvious.
-organ weights:
kidneys: relative weights raised in all tested dose groups from 500 - 2000 ppm, absolute weights raised in the 800 ppm and both 1000 ppm groups.
liver: reduced absolute weights in the 500 ppm and the 2000ppm groups, relative and absolute weight raised in the 1000ppm group treated with DOW 3-chloropropene
- Histopathology: kidney: acute tubular degeneration at 300 ppm and above in females and at 500 ppm and above in males
- Potential target organs: kidney

Any other information on results incl. tables

- table 2: mortality of male and female Fischer 344 rats exposed to allyl chloride vapor for a single 6-hour period

Vapor Conc. (ppm)		Males				Females
	During Exposure	24 Hours Postexposure	72 Hours Postexposure	Cum.Total.Dead	During Exposure	24 Hours Postexposure	72 Hours Postexposure	Cum.TotalDead
200^a	0/10	0/10	0/5	0/10	0/10	0/10	0/5	0/10
300^a	0/10	0/10	0/5	0/10	0/10	0/10	0/5	0/10
500	0/10	0/10	0/5	0/10	0/10	0/10	0/5	0/10
800	0/10	0/10	0/5	0/10	0/10	0/10	0/5	0/10
1000^a	0/10	1/10	0/5	1/10	0/10	0/10	1/5	1/10
1000^b	0/10	0/10	0/0	0/10	0/10	1/10	0/0	1/10
(Dow)
1000^b	0/10	0/10	0/0	0/10	0/10	0/10	0/0	0/10
(Shell)
2000^c	0/10	1/10	0/0	1/10	2/10	8/10	0/0	10/10

All data listed as number of dead during each interval/the total number of animals remaining at the start of the interval.

a: 200 ppm animals were sacrificed at 48 or 168 hours post exposure;

300 ppm animals were sacrificed at 48 or 144 hours post exposure; and

1000 ppm animals were sacrificed at 24 or 120 hours post exposure rather than at 24 or 72 hours.

b: All remaining animals were sacrificed at 24 hours post exposure.

c: The second 5 male rats in this group were sacrificed at 48 hours post exposure.

- table 3: animal observations on male and female Fischer 344 rats exposed to allyl chloride vapor for a single 6-hour period

Vapor Concentration (ppm)	Time of Complete Recovery from Observed Effects of Exposure (hours postexposure)	Observations on Rats After Exposurea *
		Palpebral Closure and Conjunctival Hyperemia	Nasal Discharge	Diarrhea	Lethargy	Decreased Urine and Feces	Generally Unthrifty Appearance
200	18	slight     (in only 6 of 10 rats)	-	-	-	-
300	18	slight	-	-	-	-	-
500	24	moderate	-	X	X	X	‑
800	24	moderate	-	X	X	X	‑
1000	72	severe	-	X	X	X	X
1000 (Dow)	sacrificed - 24 not recovered	severe	-	X	X	-	X
1000       (Shell)	sacrificed - 24. not recovered	severe	X	X	X	X	X
2000	males - sacrificed - 48, not recovered females - died spontaneously - 24, not recovered	severe	X	-	X	-	X

- Indicates not observed.

X Indicates an observed condition.

* Remaining animals were observed for exposure-related effects immediately upon removal from the exposure chambers, on the following morning at 18 hours postexposure, 24 hours post exposure, 48 hours postexposure and at 72 hours post exposure.

- table 4: mean (2 standard deviation) body weights of male and female Fischer 344 rats exposed to allyl chloride vapors for a single 6-hour period

Vapor Conc. (Pom)	Sex	Pre-exposure Weight (grams)	% Change from Pre-exposure to 24 hours Post-exposure	Weight After 24 Bra (grams)	% Change from Pre-exposure to 72 hours Past-exposure	Weight After 72 Mrs (grams)
0	M	204.5 ± 6.1(10)	-2.8	198.8 ± 4.1(5)	+4.4.	213.6 ± 8.2(5)
500	M	202.9 ± 8.1(10)	-6.7	189.4 ± 7.0(5)	-4.5	193.8 ± 9.4(5)
0	F	129.7 ± 5.4(10)	+0.2	130.0 ± 4.3(5)	-0.7	128.8 ± 6.1(5)
500	F	138.1 ± 4.5(10)	-8.2	126.8 ± 3.9(5)	-9.2	125.4 ± 4.1(5)
0	M	192.5 ± 6.1(10)	+3.0	198.2 ± 4.2(5)	+8.5	208.8 ± 6.2(5)
800	M	205.0 ± 6.6(10)	-8.7	187.2 ± 9.5(5)	-1.9	201.2 ± 8.9(5)
0	F	131.4 ± 6.0(10)	+1.2	133.0 ± 3.7(5)	+9.9	144.4 ± 8.6(5)
800	F	131.3 ± 4.7(10)	-7.4	121.6 ± 4.4(5)	-4.5	125.4 ± 6.2(5)
0	M	254.2 ± 14.3(5)	+5,8	269.0 ± 15.4(5)
1000 (Shell) a	M	288.7 ± 12.3(10)	-11.9	254.4 ± 10.9(10)
0	F	145.6 ± 3.7(5)	+7.1	156.0 ± 4.7(5)
1000 (Shell) a	F	158.5 ± 5.4(10)	-12.1	139.3 ± 5.1(10)
0	M	285.2 ± 11.4(5)	-0.4	284.0 ± 12.4(5)
1000 (Dow) a	M	284.9 ± 25.1(10)	-12.1	250.5 ± 8.3(10)
0	F	161.8 ± 3.4(5)	+0.4	162.4 ± 3.0(5)
1000 (Dow) a	F	165.6 ± 5.9(10)	-13.2	143.8 ± 6.8(10)
0 b	M	196.5 ± 10.4(10)	+0.5	197.4 ± 10.1(5)	-1.1	194.4 ± 13.2(5)
2000 b	M	205.6 ± 8.6(10)	-14.9	175.0 ± 8.5(4)	-22.6	159.2 ± 7.7(5)
0	F	-	-	-	-	-
2000 c	F	-	-	-	-	-

Number of animals used to calculate the mean is in parenthesis.

a All remaining animals in these groups were sacrificed at 24 hours postexposure.

b The last mean values far the male rats in the 2000 ppm group were actually determined at 48 hours, not at 72 hours. c No female rats in the 2000 ppm group remained alive at 24 hours postexposure.

- table 5: mean analytical and nominal chamber vapor concentrations for the single 6-hour exposure studies of allyl chloride

Target Concentration (ppm)	Species Tested	Actual Analytical Concentration (ppm)^a	Nominal Concentration (ppm)^b
200	Rats	202.5	202.1
300	Rats	292.2	261.5
500	Rats and Mice	517.7	739.6
800	Rats and Mice	779.1	832.1
1000	Rats	954.1	1164.9
1000 (Shell)^c	Rats and Mice	984.4	1059.8
1000 (Dow)	Rats and Mice	1031.8	1710.8
1200	Mice	1222.9	1391.9
2000	Rats and Mice	1745.5	2496.3

a Analytical values for allyl chloride concentration were obtained from the appropriate standard curve 3 times per 6-hour exposure and the time-weighted analytical values were calculated.

b Nominal concentrations may not correspond to analytical due to variation in chamber or syringe calibrations, or surface adherence of the material. Analytical concentrations should be considered the more reliable.

c This test was conducted with allyl chloride from Shell Chemical Company. All other tests were conducted with material from The Dow Chemical Company.

Applicant's summary and conclusion

Interpretation of results:

other: clear classification not possible

Remarks:

Criteria used for interpretation of results: OECD GHS

Executive summary:

In the present study (Quast 1982) Fischer 344 rats of both sexes were treated with 3 -chloropropene once via the inhalation route for 6 hours, ten animals per sex and dosage. A determination of a LC50 value is not possible as rats were sacrificed at day 3 to 7. Based on this results a classification according to CLP in the EU (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL) is not possible.

After the single inhalative treatment animals were weighted at day one and day 3 post treatment and were observed for clinical signs pre exposure, 24 h post exposure and generally 72 h post exposure (2000 ppm males in poor condition were weighted at 48 h post exposure). 5 animals were sacrificed 24 h post treatment (at 48 h for 200 and 300 ppm animals) and the rest at different times at 3 to 7 days depending on the exposure concentrations. Gross necroscopy of survivors was performed and organ weights of liver and kidneys and several clinical chemistry parameters (BUN, SGPT, AP, SGOT and glucose) were determined. Samples of liver and kidney were analyzed histologically.

As all animals were sacrificed during the first week no clear statement is possible concerning mortality. In the 1000 ppm group occasionally animals died during the observation period, below 1000 ppm no fatalities were observed before sacrifice, at 2000 ppm all animals died within 48 h or had to be killed for humane reasons. Where body weights were recorded (500, 800 and 2000 ppm) after exposure body weights were reduced in all treatment groups. Regarding organ weights kidney effects are reported for all dose groups that were tested for organ weights (500 - 2000 ppm).

For biochemical parameters only the BUN concentration shows a clear dose dependent effects (rise) becoming statistically significant at 1000 ppm in males and at 500 ppm in females at 24 h post exposure. 72 h post exposure at some of the higher dose groups a reduction in AP activity was found but no clear trend was obvious.

Gross and microscopic findings, kidney weight changes, and elevated BUN values indicated that the kidney was the target organ in both sexes; however, the female rats were the more sensitive at each exposure concentration. Microscopic examination of the kidneys from several male and female rats exposed to 200 and 300 ppm revealed a very minimal effect in the 300 ppm females only. A recognizable exposure-related effect was not detected in males in the 200 and 300 ppm groups nor in the females in the 200 ppm group.

Data obtained from rats to compare their response following exposure to 1000 ppm of allyl chloride which was obtained either from The Dow Chemical Company or Shell Chemical Company, did not reveal a significant difference.

Based on the presented result the LD50 for direct effects of 3-chloropropene in rats after exposure via the inhalative route can be expected to lie in the region of 1000 ppm. Not covered is a possible rise in mortality in the second week after exposure, as all animals were sacrificed between day 1 and day 7 post exposure. This time span is covered by the study of Adams (1944).