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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

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 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

Ambiguity in the identification of the batch; purity of the test material not indicated; inconsistent duration of exposure (contact period): 24 or 27 hours.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

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: 277 - 312 g (males), 200 - 235 g (females)
- Fasting period before study: 16 - 20 hours
- Housing: individual, 2 per cage (separated by a solid metal partition, 1 animal per compartment) 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

Type of coverage:

occlusive

Vehicle:

sorbitan derivative

Remarks:

0.3 mL of a 0.5% polysorbate 80 solution

Details on dermal exposure:

TEST SITE
- Hair removal, by clipping, 100 x 50 mm on dorso-lumbar area
- Area of exposure: patch size approx. 75 x 50 mm
- % coverage: not reported
- Type of wrap if used: aluminium foil patch , kept in place using adhesive impermeable tape (approx. size 250 x 75 mm)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): skin cleansed using swabs of absorbent cotton wool soaked in clean warm water, then dried with tissue paper
- Time after start of exposure: 24 or 27 hours; the report is inconsistent, it states "kept in contact for 24 hours" and a "27-hour contact period"

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bodyweight (bw)
- Concentration (if solution): not reported; solid test substance weighed out onto an aluminium patch, then moistened with 0.3 mL of 5% polysorbate 80
- Constant volume or concentration used: yes (constant volume of 5% polysorbate 80)
- For solids, paste formed: yes

VEHICLE
- Amount applied (volume or weight with unit): 0.3 mL
- Concentration (if solution): 0.5%
- Lot/batch no. (if required): not reported
- Purity: not reported

Duration of exposure:

24 or 27 hours; the report is inconsistent, it states "test substance kept in contact with the skins for 24 hours" and a "27-hour contact period" in two subsequent paragraphs

Doses:

2000 mg/kg body weight (bw)

No. of animals per sex per dose:

5 males, 5 females

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: observations on day 1: once (between 1 and 4 h after dosing); once daily thereafter; weighing: day 1 (before application), days 3, 6, 8, 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

none (limit test)

Results and discussion

Preliminary study:

No details reported; used to set the nominal dose for the limit test main study (2000 mg/kg body weight)

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality

Mortality:

None

Clinical signs:

other: Signs of systemic toxicity (mostly on day 2 only): diarrhoea, stains around the nose, signs of urinary incontinence, and upward curvature of the spine. The stains persisted in one female until day 5. Signs of skin irritation: - scab formation (at edge of

Gross pathology:

No macroscopic abnormalities were observed.

Other findings:

None reported.

Any other information on results incl. tables

Table 1: Mean body weight and standard deviation (SD)

Sex	Dose		Day:					BW gain
	mg/kg bw		1	3	6	8	15
M	2000	Mean bw	293.6	279.6	292.6	309.6	331.4	37
		+/- SD	12.4	12.3	14.6	15.3	15.6
F	2000	Mean bw	213.6	209.4	215.4	222.6	234.8	21
		+/- SD	13.4	7.9	12.2	14.2	11.6

Table 2: Clinical observations: Number of animals affected and days of occurrence

Clinical observation	Males		Females
mg/kg bw	2000		2000
	animals	days	animals	days
number of animals	5		5
killed at termination	5	15	5	15
signs of diarrhoea	1	2	1	2
stains around nose	1	2	3	2-5
signs of urinary incontinence	1	2	3	2
urinary incontinence	0		1	2
upward curvature of spine	1	2	0
desquamation	0		3	4-7
skin eruptions ?	2	2-7	0
scab: edge of applic. area	0		2	6-15
scabs: small scattered	1	6-11	1	4-12

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute dermal LD50 of the test substance was estimated to be greater than 2000 mg/kg bw to male and female rats. Confidence limits could not be calculated (limit test). The study report is relevant, reliable with restrictions and adequate for risk assessment, classification and labeling.

Executive summary:

The acute dermal toxicity of the test material (a powder) was assessed according to OECD 402 in a limit test with five male and five female rats, at a dose of 2000 mg/kg body weight. The test substance was moistened with 0.3 mL of 0.5% polysorbate 80 and applied dermally as a paste, then covered with an occlusive dressing (aluminium foil). Mortalities, signs of toxicity, and body weight development were recorded during 15 days; survivors were examined by necropsy for macroscopic abnormalities.

Mortalities were not observed at this dose. Signs of systemic toxicity were mostly seen on day 2: diarrhea, stains around the nose, signs of urinary incontinence, and upward curvature of the spine. Skin irritation was observed between day 4 and 15 (scab formation in 1/5 male and 3/5 females, slight desquamation in 3/5 females). Body weights initially decreased, but reached their initial values around day 8 after treatment and increased thereafter. No macroscopical abnormalities were detected.

The author estimates an acute dermal LD50 of > 2000 mg/kg bw to both sexes.