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

Endpoint summary

Description of key information

Acute oral toxicity, rat:

The test substance is moderately toxic to rats following acute oral administration.

Some of the signs that were observed occurred immediately after administration and continued until day 5 maximum. Essentially, the following signs were observed: impaired activity and dyspnea, lethargy, piloerection, spastic or staggering gait, lateral recumbency, increased salivation, atony, convulsions, spasmodic state, no reflexes. Mortalities occurred starting at a dose of 400 mg/kg body weight. 

LD50: Rat male: 726 mg/kg body weight (approximate)

LD50: Rat female: 474 mg/kg body weight (approximate)

 

Acute inhalation, rat:

The test substanceexhibited 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.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

March - April 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1987

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Specific details on test material used for the study:

Purity: 99.2 %
Stability in formulation not tested

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

with 2% Cremophor EL (v/v)

Doses:

male: 1000, 800 and 500 mg/kg bw
female: 500, 400 and 200 mg/kg bw

No. of animals per sex per dose:

5 anmials per sex and dose

Control animals:

no

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

726 mg/kg bw

Based on:

test mat.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

474 mg/kg bw

Based on:

test mat.

Mortality:

male: 1000 mg/kg group: 4 animals died, 800 mg/kg group: 3 animals died, 500 mg/kg group: no animal died
female: 500 mg/kg group: 3 animals died, 400 mg/kg group: 1 animal died, 200 mg/kg group: no animal died

Clinical signs:

other: The following signs were observed in males at 500 mg/kg body weight and in females at 200 mg/kg body weight: piloerection, reduced or increased activity, dyspnea, spasmodic state, lateral recumbency, and spastic or staggering gait. In the males, letharg

Gross pathology:

Animals that died during the recovery period:
In a few cases, lungs pale, distended; in a few cases, liver dark, pale, mottled, lobular pattern; kidneys pale and mottled; spleen somewhat pale; in one animal, ulcer-like foci in the glandular stomach; in one animal, stomach with clear fluid or yellowish fluid content; in one animal, small intestine slightly reddened, empty; in a few cases, intestinal tract empty, reddened; mesenteric vessels severely injected; in a few cases, abdominal organs not assessable.


Animals sacrificed while moribund:
One animal: liver pale, mottled, lobular pattern; stomach with brown fluid content; glandular stomach reddened; intestinal tract reddened, partially empty.


Animals sacrificed at the end of the recovery period:
For males, no evidence of test substance-related, gross organ damage.
For females, at 500 mg/kg body weight: in a few cases, lungs slightly distended; liver with slight lobular pattern (one animal).

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The substance is harmful if swallowed.

Executive summary:

Tests were performed to determine the acute oral toxicity to male and female rats. The study was performed in accordance with the OECD Guideline for Testing of Chemicals; Section 4: Health Effects, No. 401 - "Acute Oral Toxicity," adopted February 24, 1987 (1) and in accordance with the Pesticide Assessment Guidelines, Subdivision F, Hazard Evaluation: Human and Domestic Animals, Series 81-1 Acute Oral Toxicity Study (Revised Edition, November 1984) (2).

LD50: Rat male: 726 mg/kg body weight (approximate)

LD50: Rat female: 474 mg/kg body weight (approximate).

Some of the signs that were observed occurred immediately after administration and continued until day 5 maximum. Essentially, the following signs were observed: impaired activity and dyspnea, lethargy, piloerection, spastic or staggering gait, lateral recumbency, increased salivation, atony, convulsions, spasmodic state, no reflexes. Mortalities occurred starting at a dose of 400 mg/kg body weight. The test substance is moderately toxic to rats following acute oral administration.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

474 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

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

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

Specific details on test material used for the study:

Purity: 99.2 %;
stability in vehicle tested and confirmed

Species:

rat

Strain:

Wistar

Sex:

male/female

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

Key result

Sex:

female

Dose descriptor:

LC50

Effect level:

ca. 6 800 mg/m³ air (nominal)

Based on:

test mat.

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)

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

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

6 800 mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the study results for acute toxicity allocation to category 4 for oral toxicity (H302) and no classification for inhalative toxicity according to Regulation (EC) No. 1272/2008 (CLP), ANNEX I, is warranted.