3-chloropropene

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1979-04-03 - 1980-03-31

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: - study compliant to OECD 401 - non-GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

the study was conducted to compare the sensitivity of Sprague Dawley rats and CDF rats (F-344 derived) against 6 different substance including 3-chloropropene

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
- Substance type: short chain chlorinated hydrocarbon
- Physical state: not reported
- Analytical purity: 98.6% 3-chloropropene
- Impurities (identity and concentrations): ; 0.74% isopropyl chloride; 0.40% 1,5-hexadiene; 0.14% normal propyl chloride; 0.10% 2,2- dichloropropane
- Purity test date: not reported
- Lot/batch No.: TB 06308-3
- Expiration date of the lot/batch: not reported
- Stability under test conditions: not reported, but expected to be stable
- Storage condition of test material: not reported

Test animals

Species:

rat

Strain:

other: Sprague Dawley rats and CDF rats (F-344 derived)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Spb: (Sprague-Dawley) rats (Spartan Research Animals, Inc., Haslett, Michigan)
CDF (Fischer 344-derived) rats (Charles River Breeding Laboratories, Inc., Portage, Michigan)
- Age at study initiation: 7-8 wks
- Weight at study initiation (averages): Sprague Dawley males: 308 g, Sprague Dawley females: 192 g, CDF males: 136 g, CDF females 88 g,
- Fasting period before study: 16-18 hours prior to dosing
- Housing: 2 or 3/cage
- Diet (e.g. ad libitum): commercial laboratory chow (Ralston Purina Company, St. Louis, Missouri), probably ad libitum
- Water (e.g. ad libitum): water, ad libitum
- Acclimation period: >= 1 wk


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.8
- Humidity (%): 45
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: not applicable, no vehicle used


MAXIMUM DOSE VOLUME APPLIED: 1580 mg/Kg bw

Doses:

all doses in mg/Kg bw
Male Sprague-Dawley Rat: 200, 398, 795, 1580
Female Sprague-Dawley Rat: 200, 398, 795, 1580
Male CDF Rat: 200, 398, 795, 1580
Female CDF Rat: 63, 126, 200, 398, 795, 1580

No. of animals per sex per dose:

5 rats/sex/strain

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observed each working day during the observation period; weighed immediately prior to treatment, and weekly thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: no

Statistics:

The acute oral median lethal dose, 95% confidence interval, and approximate slope of the dose-response curve for both strains for all test articles were calculated by the moving average method of Thompson and Weil (Thompson, W. R. and C. S. Weil, Biometrics, Vol. 8, No. 1, March, 1952, pp. 51-54. As implemented in a computer program (Stephan, C., 1978, personal communication)), as implemented by a computer program (Stephan, 1978).
The approximate slope was calculated as 1/2 1og10 (LD84/LD16). Because this computer program also computes LD5O's, 95% confidence intervals, and slopes by probit analysis (Finney, D. J. (1972) Probit Analysis. Third Edition, Cambridge University Press, Cambridge, England.), the values obtained from both methods of analysis are reported to assess the comparability of the 2 procedures.

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

275 mg/kg bw

95% CL:

180 - 526

Remarks on result:

other: CDF rats, moving average method

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

293 mg/kg bw

95% CL:

177 - 719

Remarks on result:

other: CDF rats, probit analysis

Effect levels 3

Sex:

male

Dose descriptor:

LD50

Effect level:

419 mg/kg bw

95% CL:

298 - 612

Remarks on result:

other: CDF rats, moving average method

Effect levels 4

Sex:

female

Dose descriptor:

LD50

Effect level:

455 mg/kg bw

95% CL:

260 - 685

Remarks on result:

other: Sprague Dawley rats, moving average method

Effect levels 5

Sex:

female

Dose descriptor:

LD50

Effect level:

435 mg/kg bw

95% CL:

241 - 751

Remarks on result:

other: Sprague Dawley rats, probit analysis

Effect levels 6

Sex:

male

Dose descriptor:

LD50

Effect level:

379 mg/kg bw

95% CL:

259 - 533

Remarks on result:

other: Sprague Dawley rats, moving average method

Mortality:

see table 1

Clinical signs:

other: Clinical signs comprised slight to extreme lethargy, diarrhea, piloerection and convulsions (1 male and one female of the 795 mg/kg group). The no. and severity of clinical signs rose dose dependently. See table 2 for details

Gross pathology:

The following lesions were found:
general: focal corneal cloudiness and accumulation of exudate around eyes
Lungs: Multiple pinpoint gray foci scattered throughout all lobes
Stomach: Thickening and roughening of nonglandular squamous epithelium, focal thickening of nonglandular stomach wall, erosion of nonglandular epithelium, firm, nodular-like foci throughout epithelial surface, perforated ulcer and fibrous adhesions between stomach and liver, spleen, or diaphragm
for details, see table 4

Any other information on results incl. tables

- Table 1: Mortality (no. of dead/no. of treated)

Dose (mg/kg)	Male Sprague-Dawley	Female Sprague-Dawley	Male CDF	Female CDF
63				0/5
126				3/10
200	0/5	0/5	0/5	1/5
398	3/5	3/5	2/5	2/5
795	5/5	4/5	5/5	5/5
1580	5/5	5/5	5/5	5/5

- Table 2: Clinical signs

Dose (mg/kg)	Signs of Toxicity	Male Sprague-Dawley	Female Sprague-Dawley	Male CDF	Female CDF
63	Slight lethargy	-		-	5/5
126	Slight lethargy			-	10/10
200	Lethargy	5/5	5/5	5/5	5/5
	Piloerection	0/5	0/5	5/5	5/5
398	Lethargy	5/5	5/5	5/5	5/5
	Diarrhea	3/5	3/5	2/5	2/5
	Piloerection	0/5	5/5	5/5	5/5
795	Extreme lethargy	5/5	5/5	5/5	5/5
	Diarrhea	5/5	4/5	5/5	5/5
	Piloerection	0/5	0/5	0/5	0/5
	Convulsions	0/5	0/5	1/5	1/5
1580	Extreme lethargy	5/5	5/5	5/5	5/5
	Severe diarrhea	5/5	5/5	5/5	5/5

- Table 3: body weight development

Dose (mg/kg)	Male Sprague-Dawley				Female Sprague-Dawley				Male CDF				Female CDF
	n	Initial Weight (g)	n	Final Weight (g)	n	Initial Weight (q)	n	Final Weight (g)	n	Initial Weight (q)	n	Final Weight (g)	n	Initial Weight (g)	n	Final Weight (gl‑
63					-		-						5	82±5	5	133±2
126			-				-				-		5	83±5	3	133±9
200	5	308±13	5	403±22	5	193±6	5	236±8	5	139±7	5	214±7	5	92±1	4	143±7
398	5	296±12	2	284±10	5	191±3	2	238±6	5	135±7	3	136±9	5	91±4	3	143±3
795	5	308±8	a		5	189±4	1	250	5	136.2±6	a		5	94±2	a
1580	5	318±13	a		5	196±12			5	135±6	a		5	88±4	a

a: No survivors

- Table 4: Results of gross necroscopy (no. of affected/no. of examined)

Gross Observations	63	126	200				398
	Female CDF	Female CDF	Male S.D.	Female S.D.	Male CDF	Female CDF	Male S.D.	Female S.D.	Male COF	Female CDF
General
No visible lesion	2/5	1/7	0/5	0/5	1/5	3/4	0/2	0/3	0/3	1/3
Focal corneal cloudiness	3/5	0/7	0/5	0/5	1/5	0/4	0/2	1/3	1/3	0/3
Accumulation of exudate around eyes	0/5	0/7	0/5	0/5	0/5	0/4	1/2	0/3	1/3	0/3
Respiratory System
Lungs
Multiple pinpoint gray foci scattered throughout all lobes	0/5	0/7	0/5	1/5	0/5	0/4	0/2	0/3	0/3	0/3
Gastrointestinal System
Stomach
Thickening and roughening of nonglandular squamous epithelium	0/5	5/7	5/5	5/5	4/5	1/4	1/2	2/3	3/3	2/3
Focal thickening of nonglandular stomach wall	0/5	0/7	1/5	3/5	.0/5	0/4	0/2	0/3	0/3	0/3
Erosion of nonglandular epithelium	0/5	0/7	0/5	0/5	0/5	0/4	1/2	2/3	2/3	0/3
Firm, nodular-like foci throughout epithelial surface	0/5	0/7	0/5	0/5	0/5	0/4	0/2	0/3	1/3	0/3
Perforated Ulcer	0/5	0/7	0/5	0/5	0/5	0/4	0/2	1/3	0/3	0/3
Fibrous adhesions between stomach and liver, spleen, or diaphragm	0/5	0/7	0/5	0/5	0/5	0/4	1/2	2/3	1/3	0/3

no survivors at higher dose levels

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Remarks:

Migrated information

Executive summary:

The present study was conducted in compliance to the OECD guideline 401. Male and female Sprague Dawley rats and CDF rats (F-344 derived) were treated once with 3 -chloropropene via gavage without vehicle observed for clinical signs, weight development and overt signs of toxicity for 14 d post administration (dosage in mg/Kg bw: 200, 398, 795, 1580, female CDF also 63 and 126). Survivors were sacrificed and subjected to gross necroscopy.

The most critical derived LD50 value was 275 mg/kg bw (180 — 526, 95 % CL) for female CDF rats. Based on the determined LD50 values the substance has to be classified as Category III (Danger, toxic if swallowed) according to CLP as implementation of UN GHS in the EU (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL).

Clinical signs comprised slight to extreme lethargy, diarrhea, piloerection and convulsions (1 male and one female of the 795 mg/kg group). The no. and severity of clinical signs rised dose dependently.

No clear dose dependent body weight effect could be stated due to the high mortality in the two high dose groups.

At terminal necroscopy of survivors focal corneal cloudiness and accumulation of exudate around eyes were found. Lungs exhibited multiple pinpoint gray foci scattered throughout all lobes. In the stomach thickening and roughening of nonglandular squamous epithelium, focal thickening of nonglandular stomach wall, erosion of nonglandular epithelium, firm, nodular-like foci throughout epithelial surface and perforated ulcers were found. In addition fibrous adhesions between stomach and liver, spleen, or diaphragm were seen. The severity of these findings increased generally dose dependently.