Acetamide, N-(4-fluorophenyl)-2-hydroxy-N-(1-methylethyl)-

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

January 23, 1992 - February 11, 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N-(4-fluorophenyl)-2-hydroxy-N-(propan-2-yl)acetamide

EC Number:

611-084-9

Cas Number:

54041-17-7

Molecular formula:

C11H14FN

IUPAC Name:

N-(4-fluorophenyl)-2-hydroxy-N-(propan-2-yl)acetamide

Specific details on test material used for the study:

Purity: 99.2 %;
stability in vehicle tested and confirmed

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose/head only

Vehicle:

air

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

male and female:
group 1: air control
group 2: vehicle control (polyethylene glycol 400/acetone)
group 3: 2500 nominal (301 maeasured, in vehicle); test substance-vehicle-mixture, test substance diluted to 10% (w/v)
group 4: 6802 (measured) mg/m³

No. of animals per sex per dose:

5 animals each.

Control animals:

yes

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

female

Dose descriptor:

LC50

Effect level:

ca. 6 800 mg/m³ air (nominal)

Based on:

test mat.

Effect levels 2

Key result

Sex:

female

Dose descriptor:

other: NOEL

Effect level:

< 301 mg/m³ air (nominal)

Based on:

test mat.

Mortality:

3 femals of dose group 4 died.

Clinical signs:

irregular respiration

Remarks:

effects regarded as indicative of an irritant effect of the test substance: bradypnea and labored breathing including gasping, rales, serous nasal discharge, bloody incrustations around the nose, hypothermia, corneal opacity

Body weight:

A temporary body weight loss was determined for the animals of Groups 3 and 4.

Gross pathology:

Rats sacrificed at the end of the recovery period: No particular indications of substance-induced effects were found. The not completely collapsed lungs in two females of Group 4 are regarded as sacrifice-related findings.

Rats that died during the studv: Lungs not completely collapsed, reddish and mottled; liver pale and with lobulation; spleen pale; glandular stomach with bloody ulcerative changes; duodenum reddish and with mucoid, yellowish-black and bloody content, kidneys pale; renal pelvis reddish.

Other findings:

nonspecific clinical signs (piloerection and unpreened fur, reduced motility, vocalization, staggering gait, atony, sternal recumbency, comatose state, body weight loss, impairment of the pinnal reflex, the reaction to noises and righting reflex)

Any other information on results incl. tables

Group	Concentration (mg/m3)		Tox results	Duration of signs	Time of death	Particles ≤ 3µm (5)
	nominal	analyt.	male rats
1	air control		0/0/5	-	-	-
2	Vehicle control		0/5/5	4-5h	-	93
3	2500	301	0/0/5	-	-	89
4	-	6802	0/5/5	4h-11d	-	69
Group	Concentration (mg/m3)		Tox results	Duration of signs	Time of death	Particles ≤ 3µm (5)
	nominal	analyt.	female rats
1	air control		0/0/5	-	-	-
2	Vehicle control		0/5/5	4-5h	-	93
3	2500	301	0/0/5	-	-	89
4	-	6802	3/5/5	4h-5d	1d	69

LC50 (females): approximately 6800 mg/m3                                                     

Group 1: 15 liters air/minute                                                                                                   

Group 2: 1000 /µl vehicle (polyethylene glycol 400/acetone)/minute, 15 liters air/minute           

Group 3: 375/µl test substance-vehicle-mixture/minute, test substance diluted to 10% (w/v) in vehicle, 15 liters air/minute                                                                                                       

Group 4: Collision-Nebulizer: 6 liters air/minute + 17 liters dilution air/minute                                                                                                 

                                                                                                             

The numbers in the "Tox. Results" column of Table 1 have the following meanings:                       

1st number = number of animals that died                                                         

2nd number = number of animals with signs                                                       

3rd number = number of animals tested

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

LC50 Inhalation (Exposure: 4 hours);
Rat female : approx. 6800 mg/m3 (6.8 mg/l);
NOEL < 301 mg/m3

Executive summary:

Tests were performed to determine the acute inhalation toxicity in accordance with OECD Guideline No. 403.

The test substance-aerosol exhibited a slight acute inhalation toxicity in rats. The death and the clinical signs of the animals are regarded as causally related to an irritant effect of the test substance on the respiratory tract. In addition to nonspecific effects to the central nervous systems, the rats exposed to the 6802 mg/m3 exhibited clear signs of an irritant effect: bradypnea and labored breathing including gasping, rales, serous nasal discharge, bloody incrustations around the nose, hypothermia and corneal opacity.