N-[2-(3-carbamoyl-4-hydroxyphenyl)-2-oxoethyl]-N-(4-phenylbut-2-yl)ammonium chloride

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Data source

Reference

Reference Type:

secondary source

Title:

LABETALOL HCL (labetalol hydrochloride)

Year:

2014

Bibliographic source:

Daily Med Current Medication Information

Materials and methods

Principles of method if other than guideline:

Methods not published

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

5-[1-hydroxy-2-[(1-methyl-3-phenylpropyl)amino]ethyl]salicylamide monohydrochloride

EC Number:

251-211-1

EC Name:

5-[1-hydroxy-2-[(1-methyl-3-phenylpropyl)amino]ethyl]salicylamide monohydrochloride

Cas Number:

32780-64-6

IUPAC Name:

2-hydroxy-5-{1-hydroxy-2-[(1-methyl-3-phenylpropyl)amino]ethyl}benzamide hydrochloride

Test animals

Species:

other: rat and rabbit

Strain:

not specified

Administration / exposure

Route of administration:

oral: unspecified

Results and discussion

Results (fetuses)

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

Teratogenic studies were performed with labetalol in rats and rabbits at oral doses up to approximately six and four times the maximum recommended human dose (MRHD), respectively. No reproducible evidence of fetal malformations was observed. Increased fetal resorptions were seen in both species at doses approximating the MRHD. A teratology study performed with labetalol in rabbits at IV doses up to 1.7 times the MRHD revealed no evidence of drug related harm to the fetus.

Nonteratogenic Effects: Hypotension, bradycardia, hypoglycemia, and respiratory depression have been reported in infants of mothers who were treated with labetalol HCl for hypertension during pregnancy. Oral administration of labetalol to rats during late gestation through weaning at doses of two to four times the MRHD caused a decrease in neonatal survival.

Applicant's summary and conclusion

Conclusions:

Teratogenic studies were performed with labetalol in rats and rabbits at oral doses up to approximately six and four times the maximum recommended human dose (MRHD), respectively. No reproducible evidence of fetal malformations was observed. Increased fetal resorptions were seen in both species at doses approximating the MRHD. A teratology study performed with labetalol in rabbits at IV doses up to 1.7 times the MRHD revealed no evidence of drug related harm to the fetus.
Nonteratogenic Effects: Hypotension, bradycardia, hypoglycemia, and respiratory depression have been reported in infants of mothers who were treated with labetalol HCl for hypertension during pregnancy. Oral administration of labetalol to rats during late gestation through weaning at doses of two to four times the MRHD caused a decrease in neonatal survival.

On the base of the available data on the similar substance Labetalol Hydrochloride, the substance is suspected of damaging the unborn child.