Ethyl [2-(4-phenoxyphenoxy)ethyl]carbamate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Jun/Jul 1980 to Sep/Oct 1980

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Ethyl [2-(4-phenoxyphenoxy)ethyl]carbamate

EC Number:

276-696-7

EC Name:

Ethyl [2-(4-phenoxyphenoxy)ethyl]carbamate

Cas Number:

72490-01-8

Molecular formula:

C17 H19 N O4

IUPAC Name:

ethyl [2-(4-phenoxyphenoxy)ethyl]carbamate

Test animals

Species:

rat

Strain:

Sprague-Dawley

Remarks:

CD

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females nulliparous and non-pregnant: yes
- Age at study initiation: Young adult : 7 – 9 weeks
- Weight at study initiation: 195 – 263 g
- Housing: singly in metal cages with wire mesh floors.
- Diet: standard laboratory rodent diet, ad libitum.
- Water: provided, ad libitum.
- Acclimation period: at least 3 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24 - 25
- Humidity (%): 51 (mean)
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: Jun/Jul 1980 To: Sep/Oct 1980

Administration / exposure

Type of coverage:

occlusive

Vehicle:

corn oil

Details on dermal exposure:

TEST SITE
- Area of exposure: dorso-lumbar region
- % coverage: 10 % of the total body surface
- Type of wrap if used: The treated area was covered with aluminium foil held in place with an impermeable dressing encircled firmly round the trunk.

REMOVAL OF TEST SUBSTANCE
- Washing: After 24 hours, the dressings were removed and treated area was washed with warm (40 – 50 °C) water and finally blotting dry with absorbent paper.

TEST MATERIAL
- Amount applied: not exceeding 5 mL/kg
- Concentration: 40 % w/v test substance suspended in corn oil
- Constant volume or concentration used: yes

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw (Study 1 and 2)

No. of animals per sex per dose:

5 (Study 1 and 2)

Control animals:

yes, concurrent vehicle

Remarks:

Only study 1

Details on study design:

TEST PROCEDURE/ DESIGN:
- Study 1: A group of 5 male and 5 female rats was treated at 2000 mg/kg which was considered to be the maximum practical dose. A vehicle control group of 5 male and 5 female rats was treated with corn oil at the same dose volume as the test group.
- Study 2: A further 5 male (numbered 1 to 5 inclusive) and 5 female (numbered 6 to 10 inclusive) rats were treated at 2000 mg/kg in order to provide tissues for histopathological examination.

- Duration of observation period following administration: 14 days.
- Frequency of weighing: Individual body weights of the animals were recorded on Days 1, 8 and 15.
- Frequency of observations: Animals were observed immediately after dosing and at approximately intervals for the remainder of Day 1. On Day 2 the animals were observed once in the morning and once at the end of the experimental day. On subsequent days the animals were observed once in the morning and once at the end of the experimental day (Study 2) or once daily (Study 1).
- Necropsy of survivors performed: yes, on Day 15 and were subjected to a macroscopic post mortem examination. The macroscopic appearance of abnormal organs was recorded.
- Clinical signs: Clinical signs were recorded at each observation time. The nature, severity, approximate time of onset and duration of each toxic sign. Local dermal reactions were recorded 24 hours after application of the test material and daily thereafter. The dermal reactions were assessed on a numerical basis according to the arbitrary scoring system as mentioned in Table 1 of' Any other information on materials and methods incl. tables'.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed in either study.

Clinical signs:

other: In Study 1, there was no observable dermal irritation at the site of application in either the treated or control animals. In Study 2, 5/10 test substance exposed rats showed lethargy, and 1/10 showed decreased respiratory rate. There was no dermal irrita

Gross pathology:

Histopathology on study 2 animals showed small focal areas of epidermal ulceration with an associated acute inflammatory cell infiltration into the superficial dermis in the treated skin area of 2 females.
All animals showed minimal mononuclear cell aggregations and/or occasional foci of extramedullary haemopoiesis in the liver. 4/10 rats showed minor lesions in the kidneys.
Terminal autopsy findings were considered to be within normal limits.

Any other information on results incl. tables

Table 2 Mortality ratio, and group mean body weights (g) of rats dosed percutaneously with test substance

(Study 1)

Sex	Dosage (g/kg)	Body Weight (g) at			Mortality ratio (No of deaths)/No dosed)
		Dosing	1 week	2 weeks
males	0	250 253	291 281	340 325	0/5
		241	279	334
		238	285	334
		251	286	332
	Mean	247	284	333
	2.0	234	263	299	0/5
		240	285	331
		253	302	361
		228	277	322
		245	275	305
	Mean	240	280	324
females	0	222 241	239 257	279 284	0/5
		244	262	281
		248	265	300
		227	240	261
	Mean	236	253	281
	2.0	230	244	271	0/5
		221	234	258
		242	259	272
		232	246	271
		223	247	272
	Mean	230	246	269

Table 3 Mortality ratio, and group mean body weights (g) of rats dosed percutaneously with test substance

(Study 2)

Sex	Dosage (g/kg)	Body weight at			Mortality ratio (no of deaths / no dosed)
		Dosing	1  week	2 weeks
males	2.0	240	270	299	0/5
		263	309	360
		251	300	344
		248	290	326
		246	296	341
	Mean	250	293	334
females	2.0	212	218	241	0/5
		205	219	229
		216	231	250
		200	208	209
		214	228	236
	Mean	209	221	233

 

 

Table 4 Signs of reaction to treatment ratio of rats percutaneously with test substance

(Study 2)

Signs	Signs of reaction ratio (No showing signs/ No. dosed)
	Dose (g/kg)
	2.0
Lethargy Decreased respiratory rate	5/10 1/10

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute median lethal percutaneous dose (LD50) to rats of test substance was found to be greater than 2000 mg/kg bw which was considered to be the maximum practical dosage under the conditions of this test.

Executive summary:

An acute dermal study was performed in accordance with OECD TG 402 following GLP principles. The test was conducted with Sprague-Dawley derived rats to determine the potential for the test substance to produce toxicity from a single topical application. Two studies were performed; the first (Study 1) include a group of 5 male and 5 female rats was treated at 2000 mg/kg which was considered to be the maximum practical dose. A vehicle control group of 5 male and 5 female rats was treated with corn oil at the same dose volume as the test group. In a second study (Study 2) a further 5 male and 5 female rats were treated at 2000 mg/kg in order to provide tissues for histopathological examination. Animals were observed immediately after dosing and at approximately intervals for the remainder of Day 1. On Day 2 the animals were observed once in the morning and once at the end of the experimental day. On subsequent days the animals were observed once in the morning and once at the end of the experimental day (Study 2) or once daily (Study 1). 

No mortality was observed. From Study 2, 5/10 rats showed lethargy, and 1/10 showed decreased respiratory rate. In Study 1, no effects on body weight gain were observed. In Study 2, 2/5 females showed a decreased body weight gain during the first week, and 3/5 females during the second week, compared to the controls of Study 1. Histopathology on Study 2 animals showed small focal areas of epidermal ulceration with an associated acute inflammatory cell infiltration into the superficial dermis in the treated skin area of 2 females. All animals showed minimal mononuclear cell aggregations and/or occasional foci of extramedullary haemopoiesis in the liver. 4/10 rats showed minor lesions in the kidneys. 

The LD50 of the test substance after single dermal administration to rats of both sexes, observed over a period of 14 days is greater than 2000 mg/kg bw which was considered to be the maximum practical dosage under the conditions of this test.