Carbamic acid, N-[[5-[[[2-[2-(dimethylamino)ethoxy]ethoxy]carbonyl]amino]-1,3,3-trimethylcyclohexyl]methyl]-, 2-[2-(dimethylamino)ethoxy]ethyl ester

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21 May - 11 Jun 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-Guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Remarks:

incl. certificate for RCC Ltd 4452 Itingen from Swiss Federal Office of Public Health

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

441-100-8

EC Name:

-

Cas Number:

351197-46-1

Molecular formula:

Hill formula: C24 H48 N4 O6 CAS formula: C24 H48 O6 N4

IUPAC Name:

2-[2-(dimethylamino)ethoxy]ethyl N-{[1,3,3-trimethyl-5-(9-methyl-2-oxo-3,6-dioxa-1,9-diazadecan-1-yl)cyclohexyl]methyl}carbamate

Details on test material:

- Name of test material (as cited in study report): UAX-1179
- Physical state / appearence: pale, amber liquid
- Analytical purity: >99% proprietary tertiary amines
- Density: approx. 1.05 g/mL
- Lot/batch No.: M. 17-08.01
- Expiration date of the lot/batch: 19-Sep-2003
- Storage condition of test material: In the original container, at room temperature (range of 20 +/- 3 °C), away from direct sunlight, heat and moisture. The sample is to be stored under dry air (nitrogen).
- Safety Precautions: Routine hygienic procedures were used to ensure the health
and safety of the personnel

Test animals

Species:

rat

Strain:

other: HanBrl: WIST (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd, Biotechnology and Animal Breeding Division, CH-4414 Fiillinsdorf / Switzerland
- Age at study initiation: Males: 9 weeks, Females: 12 weeks
- Weight at study initiation: range 185.4 - 258.3 g
- Housing: During acclimatization in groups of five per sex in Makrolon type-4 cages with standard softwood bedding. Individually in Makrolon type-3 cages with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz) during treatment and observation.
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 1/02 (Provimi Kliba AG, CH- 4303 Kaiseraugsv Switzerland) ad libitum. Results of analyses for contaminants are archived at RCC Ltd, Itingen.
- Water (e.g. ad libitum): Community tap water from Fijllinsdorf ad libitum. Results of bacteriological, chemical and contaminant analyses are archived at RCC Ltd, Itingen.
- Acclimation period: one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 °C
- Humidity (%): 30 - 70%
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12
- music during the light period

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

other: none

Details on dermal exposure:

TEST SITE
- Area of exposure: on the back
- % coverage: 10% of the total body surface
- Type of wrap if used: The dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): flushed with lukewarm water
- Time after start of exposure: 24 hours after the application

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.9 mL (x 1.05 g/mL = 2000 mglkg)

VEHICLE
- undiluted

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of weighing: On test days 1 (prior to administration), 8 and 15.
- Frequency of observations (Mortality / Viability): Daily during acclimatization and twice daily during days 1-15.
- Frequency of observations (Clinical signs): Daily during acclimatization and at approximately 1, 2, 3 and 5 hours after administration on test day 1. Once daily during days 2-15. All abnormalities were recorded.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic examinations

Statistics:

No statistical analysis was used.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0 Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0

No deaths occured during the study.

Clinical signs:

other: Signs of toxicity related to dose levels: No systemic signs of toxicity were observed during the study.

Gross pathology:

No macroscopic findings were observed at necropsy.

Other findings:

Signs of toxicity (local): Slight erythema was observed in all male and female animals from test day 2 after removal of the dressing to test day 5 and persisted until test day 6 in two male animals until test day 9 in one male and three female animals.

Any other information on results incl. tables

The median lethal dose of UAX-1179 after single dermal administration to rats of both sexes,

observed over a period of 14 days is:

LD50 (rat): > 2000 mg/kg body weight

Table 1: Body weights (in grams)

Sex / Dose	Animal. No.	Day of Treatment	Day 8	Day 15
male / 2000 mg/kg	1	257.7	271.4	296.8
	2	255.9	283.7	309.2
	3	253.0	261.2	290.9
	4	258.3	273.4	301.5
	5	239.9	256.0	277.5
female / 2000 mg/kg	6	207.0	205.6	217.3
	7	205.2	206.9	208.0
	8	199.4	214.6	215.6
	9	194.9	198.7	199.0
	10	185.4	193.3	196.5

Table 2: Clinical / Local signs

			Test day
Sex / Dose	Animal No.	Signs	1				2	3	4	5	6	7	8-9	10-15
			1*	2*	3*	5*
male / 2000 mg/kg	1	No clinical signs	/	/	/	/								/
		Erythema	-	-	-	-	1	1	1	1	1	1	1
	2	No clinical signs	/	/	/	/					/	/	/	/
		Erythema	-	-	-	-	1	1	1	1
	3	No clinical signs	/	/	/	/						/	/	/
		Erythema	-	-	-	-	1	1	1	1	1
	4	No clinical signs	/	/	/	/					/	/	/	/
		Erythema	-	-	-	-	1	1	1	1
	5	No clinical signs	/	/	/	/						/	/	/
		Erythema	-	-	-	-	1	1	1	1	1
female / 2000 mg/kg	6	No clinical signs	/	/	/	/					/	/	/	/
		Erythema	-	-	-	-	1	1	1	1
	7	No clinical signs	/	/	/	/					/	/	/	/
		Erythema	-	-	-	-	1	1	1	1
	8	No clinical signs	/	/	/	/								/
		Erythema	-	-	-	-	1	1	1	1	1	1	1
	9	No clinical signs	/	/	/	/								/
		Erythema	-	-	-	-	1	1	1	1	1	1	1
	10	No clinical signs	/	/	/	/								/
		Erythema	-	-	-	-	1	1	1	1	1	1	1

1 slight, / noted, - semi-occlusive dressing present; no reading of the local signs

*Examination performed approximately 1,2,3 and 5 hours after treatment.

No clinical signs were evident in any animal during the acclimatization period.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 of UAX-1179 after dermal application to rat is > 2000 mg/kg body weight.

Executive summary:

After dermal application of 2000 mg/kg bw of the undiluted test item for 24 hours, no deaths occurred during the GLP-Guideline study. Slight erythema was observed in all animals. The median lethal dose of UAX-1179 after a single dermal administration to rats of both sexes, observed over a period of 14 days is greater than 2000 mg/kg body weight.