Erythromycin

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

June and July 1985

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Limit dose study (5000 mg/kg) conducted to GLP. Study was conducted following a standard protocol and in accordance with GLP. The study material is well characterized. supporting study only.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

GLP compliance:

yes

Test type:

other: Limit dose study

Test material

Test material information

Constituent 1

Reference substance name:

Erythromycin

EC Number:

204-040-1

EC Name:

Erythromycin

Cas Number:

114-07-8

Molecular formula:

C37H67NO13

IUPAC Name:

6-{[4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy}-14-ethyl-7,12,13-trihydroxy-4-[(5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl)oxy]-3,5,7,9,11,13-hexamethyloxacyclotetradecane-2,10-dione (non-preferred name)

Test animals

Species:

other: Mice and rats

Strain:

other: ICR mice and Crl:Co®(SD)BR rats

Sex:

male/female

Details on test animals or test system and environmental conditions:

Male and female ICR mice weighing 18 to 26 g each (approximately 5 to 6 weeks old) and male and female Crl:co®(SD)BRRats 4 weighing 107 to 135 g each (approximately 5 to 6 weeks old) were used. Following treatment the mice and rats were housed in stainless steel cages with one rat or five mice of the same sex per cage.Ambient temperature was monitored during the study and was
maintained at approximately 71 to 75°F.5 Certified Rodent Chow® #50026 and tap water
were provided ad libitum. Routine and special analyses were conducted on feed and water to assu re that contaminants were not present at levels which would compromise the interpretation of this s tudy. No potential contaminants were identified which could have been expected to affect the study outcome . The cages, cage racks and animal room were kept clean throughout the study.

The animals were allowed to acclimatize to the animal care facilities for 6 or 7 days before treatment. Food was withheld from the mice for a period of 30-60 minutes and rats were fasted overnight before
treatment.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: hydroxypropylmethylcellulose

Details on oral exposure:

dose level: 5000 mg/kg (5 g/kg)
concentration: 20 ml/kg

Doses:

The test suspension was administered one time by gavage to all animals at a dose of 20 ml/kg (5 g A BBOTT-56268/kg); this was considered the maximum volume that could be administered to mice and rats as a single treatment.

No. of animals per sex per dose:

5 females/males per dose rats and mice

Control animals:

yes

Details on study design:

All animals were observed frequently on the day of treatment and at least once daily for the following two weeks for fatalities and for signs of toxicity . All animals were weighed weekly.

At the end of the observation period the animals were killed by ascending concentrations of carbon dioxide. All animals were subjected to gross pathological observations. . No tissues were retained.

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: rats

Effect levels 2

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: mice

Mortality:

Mice exhibited no signs of toxicity and none of the mice died. One male rat was found dead 5 days after treatment.

Clinical signs:

other: Decreased activity was observed in the rats at approximately four hours after treatment, but the rats appeared normal later the same day. Increased amounts of loose hair were observed beneath the cages of the rats 6-8 days after treatment

Gross pathology:

Necropsy of the rat that died revealed only that the rat was dehydrated. Dilatation of the renal pelvis was found in one male rat when the remaining mice and rats were killed and necropsied two weeks after treatment. No other gross morphologic changes were found.

Other findings:

ABBOTT-56268 was practically non-toxic to mice and rats. Mice exhibited no adverse effects and
rats generally exhibited only mild effects (e.g., decreased activity, hair loss and slightly reduced body weight gains) following treatment with the largest dose that could be administered, 5 g/kg. The death of one rat occurred 5 days after treatment and, therefore, may not have been related to treatment with ABBOTT-56268. Dilatation of the renal pelvis of one rat killed two weeks after treatment was not considered drug-related.

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Conclusions:

The acute oral median lethal dose (LD50) of the test material was 5 g/kg.
ABBOTT-56268 was practically non-toxic to mice and rats. Mice exhibited no adverse effects and ra ts generally exhibited only mild effects (e.g., decreased activity, hair loss and slightly reduced body weight gains) following treatment with the largest dose that could be administered, 5 g/kg. The death of one rat occurred 5 days after treatment and, therefore, may not have been related to treatment wi th ABBOTT-56268. Dilatation of the renal pelvis of one rat killed two weeks after treatment was not considered drug-related.