Cyclopropanecarboxylic acid, 3-[(1Z)-2-chloro-3,3,3-trifluoro-1-propen-1-yl]-2,2-dimethyl-, (1R,3R)-rel-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1984-01 to 1984-06-05

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1984

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

Ambiguity in the identification of the batch; purity of the test material was not indicated.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

reaction mass of (1R,3R)-3-[(1Z)-2-chloro-3,3,3-trifluoroprop-1-en-1-yl]-2,2-dimethylcyclopropanecarboxylic acid and (1S,3S)-3-[(1Z)-2-chloro-3,3,3-trifluoroprop-1-en-1-yl]-2,2-dimethylcyclopropanecarboxylic acid

EC Number:

614-283-9

Cas Number:

68127-59-3

Molecular formula:

C9H10ClF3O2

IUPAC Name:

reaction mass of (1R,3R)-3-[(1Z)-2-chloro-3,3,3-trifluoroprop-1-en-1-yl]-2,2-dimethylcyclopropanecarboxylic acid and (1S,3S)-3-[(1Z)-2-chloro-3,3,3-trifluoroprop-1-en-1-yl]-2,2-dimethylcyclopropanecarboxylic acid

Details on test material:

- Physical state: crystalline powder
- Colour: white
- Expiration date of the lot/batch: not reported
- Storage condition of test material: not reported

Test animals

Species:

rat

Strain:

other: Alderley Park specific pathogen free (SPF) albino rats

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 5 -7 weeks
- Weight at study initiation: 144 - 182 g (males), 124 - 155 g (females)
- Fasting period before study: 16 - 20 hours
- Housing: 5 per cage, in stainless steel cages, 370 x 320 x 200 mm; floor and back: 12 mm square mesh, door: Makrolon (polycarbonate);
- Water: tap water ad libitum, via an automatic system
- Acclimation period: >= 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): approx. 21°C, constantly recorded
- Humidity (%): approx. 55% relative, constantly recorded
- Air changes (per hr): 20 - 30
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: To: not reported

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Remarks:

suspension

Details on oral exposure:

VEHICLE
- Concentration in vehicle: nominal 100, 200, 500 mg/mL, analytically determined 97, 202, 499 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg body weight, except males at 1000 mg/kg, which received 11 mL/kg.
- Justification for choice of vehicle: not reported
- Lot/batch no. (if required): not reported
- Purity: not reported

MAXIMUM DOSE VOLUME APPLIED: 11 mL/kg
- Rationale for the selection of the starting dose: Results from preliminary study with small number of animals (not further specified)

Doses:

nominal: 1000 (males only), 2000, 5000 mg/kg
analytically determined: 1067 (dosing volume adjusted to low analytical concentration), 2020, 4990 mg/kg

No. of animals per sex per dose:

5 males, 5 females

Control animals:

other: not required

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: observations on day 1: twice (30-90 min and 4-6 h after dosing); once daily thereafter; weighing: day -1 (before fasting and application), days 1, 3, 6 (or 4, in lowest dose group), 8, 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

None

Results and discussion

Preliminary study:

No details reported; used to set three nominal doses for main study (1000, 2000, 5000 mg/kg body weight)

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 4 990 mg/kg bw

Based on:

test mat.

Remarks:

analytical determination

Remarks on result:

other: Maximum mortality 2/5 at 2020 mg/kg bw, lower mortality (1/5) at 4990 mg/kg bw, no meaningful statistical calculation possible

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 4 990 mg/kg bw

Based on:

test mat.

Remarks:

analytical determination

Remarks on result:

other: Maximum mortality 2/5 at 4990 mg/kg bw, no meaningful statistical calculation possible

Mortality:

All deaths occurred within 48 hours after application.
Males: 0/5 at 1067 mg/kg bw, 2/5 at 2020 mg/kg bw, 1/5 at 4990 mg/kg bw
Females: 0/5 at 2020 mg/kg bw, 2/5 at 4990 mg/kg bw

Clinical signs:

other: Most common signs of toxicity: decreased activity, piloerection, dehydration and signs of urinary incontinence, stains (partially bloody) around the nose, upward curvature of the spine. In the lowest dose group (1067 mg/kg bw, males only), symptoms start

Gross pathology:

No macroscopic abnormalities were observed.

Other findings:

None reported

Any other information on results incl. tables

Table 1: Cumulative mortality

Sex	Day	1067	2020	4990
		mg/kg bw	mg/kg bw	mg/kg bw
Males	1	0/5	2/5	0/5
	2	0/5	2/5	1/5
	15	0/5	2/5	1/5
Females	1	not tested	0/5	0/5
	2	not tested	0/5	2/5
	15	not tested	0/5	2/5

Table 2: Mean body weight and standard deviation (SD)

Sex	Dose		Day:							BW gain
	mg/kg bw		-1	1	3	4	6	8	15	survivors
M	1067	Mean bw	154.2	133.8	162.4	171.2		205.2	265.0	110.0
		+/- SD	13.9	13.6	10.7	10.6		11.8	14.0
M	2020	Mean bw	169.4	148.4	174.3		201.7	217.7	274.3	97.0
		+/- SD	11.4	9.4	12.5		11.1	15.0	16.2
M	4990	Mean bw	167.0	145.4	162.0		189.0	200.0	264.8	100.0
		+/- SD	9.5	10.6	9.4		5.6	5.7	8.7
F	2020	Mean bw	138.0	119.0	141.2		157.6	164.8	196.6	59.0
		+/- SD	6.0	5.6	6.8		9.0	7.5	9.2
F	4990	Mean bw	136.2	117.4	128.3		150.0	156.0	188.7	57.0
		+/- SD	11.6	11.5	6.4		11.1	8.7	11.8

Table 3: Clinical observations: Number of animals affected and days of occurrence

Clinical observations Males	group 03		group 01		group 02
mg/kg bw	1067		2020		4990
Males: number of animals	5		5		5
	animals	days	animals	days	animals	days
activity decreased		1	2	1	4	1-4
found dead	0		2	1	1	2
killed termination	5	15	3	15	4	15
signs of diarrhoea	1	3	0	3	0
splayed gait	1	1	0		1	1
reduced stability	3	1	2	1	3	1-2
tip toe gait	0		1	1	1	1
chromodacryorrhea	0		0		2	2-3
abdominal tone decreased	0		1	1	2	1
dehydrated	2	1	3	1-2	4	1-4
piloerection	1	1	0		3	1-5
salivation	0		0		3	1
sides pinched in	3	1	2	1	3	1-2
signs of salivation	2	1	2	1-2	2	1-3
stained around mouth	0		0		1	1-2
stains around nose	2	1	3	1-4	5	1-4
signs of urinary incontinence	2	2-4	3	2-5	4	1-5
ungroomed	0		1	1	2	2-4
urinary incontinence	0		3	1	2	1
upward curvature of spine	4	1-2	3	1-3	4	1-3
reduced righting reflex	0		1	1	2	1
breathing depth increased	0		0		1	1
breathing rate reduced	0		0		1	1

Clinical observations Females			group 01		group 02
mg/kg bw	1067		2020		4990
Females: number of animals	0		5		5
	animals	days	animals	days	animals	days
activity decreased			3	1	4	1-3
bizarre behaviour			0		1	1
tremors			0		1	1
found dead			0		2	2
killed termination			5	15	3	15
diarrhoea			1	1	0
reduced stability			3	1	3	1
chromodacryorrhea			0		1	2
abdominal tone decreased			0		3	1
dehydrated			4	1-4	5	1-3
hypothermia			0		2	1
piloerection			2	1-2	5	1-11
salivation			1	1	0
sides pinched in			3	1	4	1
signs of salivation			4	1-2	5	1-2
stains around nose			3	1-2	5	1-4
signs of urinary incontinence			3	2-4	3	1-7
ungroomed			1	3-4	3	1-4
urinary incontinence			2	1	3	1-2
hair loss (general)			0		1	6-15
upward curvature of spine			3	1	5	1-3
reduced righting reflex			1	1	3	1
breathing depth increased			1	1	1	1
breathing rate reduced			0		2	1
breathing depth reduced			1	1	1	1

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral LD50 of the test substance was estimated to be greater than 4990 mg/kg bw to male and female rats. Confidence limits could not be calculated. The study report is relevant, reliable with restrictions and adequate for risk assessment, classification and labeling.

Executive summary:

The acute oral toxicity of the test material (a powder) was assessed according to a method similar to OECD 401 in groups of five male and five female rats, at doses of 1067 (males only), 2020, and 4990 mg/kg body weight (bw). The test substance was applied as a suspension in corn oil by oral gavage. Mortalities, signs of toxicity, and body weight development were recorded during 15 days; survivors were examined by necropsy for macroscopic abnormalities.

Mortalities in all dose groups up to 4990 mg/kg bw were less than 50% (1/5 or 2/5 animals), so that a statistical calculation of the LD50 (by interpolation) could not be performed. The most common clinical symptoms were decreased activity, piloerection, dehydration, signs of urinary incontinence, stains around the nose, and upward curvature of the spine. They subsided within 3 - 7 days, except for one high-dose male. Body weights initially decreased (due to fasting), but reached their initial values around day 4 - 6 after treatment and increased normally thereafter. No macroscopical abnormalities were detected.

The author estimates an acute oral LD 50 of > 4990 mg/kg bw to male and female rats.