Phenylephrine hydrochloride

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

disregarded due to major methodological deficiencies

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Publication published in a peer reviewed journal with limitations in design and/or reporting as for instance maternal toxicity was not investigated and only one dose was tested using a non-relevant route of exposure and a small number of animals.

Data source

Reference

Reference Type:

publication

Title:

Effect of epinephrine on fetal growth and the length of gestation

Author:

Shabanah E.H., et. al.

Year:

1969

Bibliographic source:

Surg Gynecol Obstet. Aug;129(2):341-3

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Three groups of rabbits were subcutaneously injected with 1 milligram of phenylephrine hydrochloride in 1 milliliter of normal saline solution. Group 1 consisted of 10 animals of which 7 were treated three times a day from the twenty-second day of gestation and daily thereafter until delivery. The remaining three rabbits served as controls. Group 2 consisted of a similar number of rabbits of which five were similarly treated on the twenty-second day of gestation and daily thereafter. The remaining five served as controls. Group 3 consisted of two rabbits treated with phenylephrine from the sixteenth day, midpregnancy, on. After delivery pups were weighed and counted. The placentas of the two rabbits in group 3 were sectioned for histologic study of the placental vessels; their weights were also recorded. Urine samples of the two rabbits in group 3 and of two of the controls in each of groups 1 and 2 were tested for sugar, three times a day as of the fourth day of treatment.

GLP compliance:

no

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Phenylephrine hydrochloride

EC Number:

200-517-3

EC Name:

Phenylephrine hydrochloride

Cas Number:

61-76-7

Molecular formula:

C9H13NO2.ClH

IUPAC Name:

phenylephrine hydrochloride

Details on test material:

- Name of test material (as cited in study report): phenylephrine hydrochloride

Test animals

Species:

rabbit

Strain:

New Zealand White

Administration / exposure

Route of administration:

subcutaneous

Vehicle:

physiological saline

Duration of treatment / exposure:

Group 1 and 2: three times a day from the twenty-second day of gestation and daily thereafter until delivery.
Group 3: from day 16 of gestation until delivery.

Doses / concentrations

Remarks:

Doses / Concentrations:
1 mg/rabbit
Basis:
nominal conc.

No. of animals per sex per dose:

Group 1: 10 rabbits: 7 rabbits for treatment, 3 controls
Group 2: 10 rabbits: 5 rabbits for treatment, 5 controls
Group 3: 2 rabbits: 2 rabbits for treatment, no controls

Control animals:

yes, concurrent no treatment

Examinations

Maternal examinations:

The placentas of the two rabbits in group 3 were sectioned for histologic study of the placental vessels; their weights were also recorded. Urine samples of the two rabbits in group 3 and of two of the controls in each of groups 1 and 2 were tested for sugar with clinitest tablets, three times a day as of the fourth day of treatment.

Fetal examinations:

After delivery pups were weighed and counted.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Details on maternal toxic effects:
- One rabbit of group 1 had an antepartum hemorrhage on day 18, the third day after treatment.
- The average weights of the five and four available placentas in rabbits 1 and 2 were 2.4 and 4.6 grams, respectively. The histologic observations of the placentas of rabbit 1 of group 3 showed engorged maternal and fetal vascular spaces, with no appreciable changes in the vessel wall. Calcification was minimal and focal, and the necrosis was seen only in the areas of placental detachment from the uterine wall. The placentas of rabbit 2 were completely normal.
- Urine was rarely positive in the controls, sugar-free in rabbit 1 of group 3, and frequently gave a 2 plus reaction in rabbit 2 of group 3.

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Basis for effect level:

other: effect type not specified

Remarks on result:

not determinable

Remarks:

no NOAEL identified

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Details on embryotoxic / teratogenic effects:
- Group 1. Two treated rabbits each delivered five living young on the twenty-sixth day of gestation, the average birth weight being 12.91 and 12.94 grams, respectively. One rabbit delivered five living young on the thirtieth day, the average birth weight being 40.4 grams. Two rabbits delivered six and five living on the thirty-first day, the average birth weight being 36.6 and 35.5 grams, respectively. The last two rabbits in this group delivered four and six young on the thirty-second day, average birth weight being 35.5 and 34.2 grams, respectively - mean normal, 48.7 ± 3.8 grams. Two controls delivered on the thirty-third day and the third, the thirty-fourth day, five, five, and four living young, respectively, average birth weight being 48.5, 49.8, and 44.8 grams, respectively.
- Group 2. Three treated rabbits delivered four, four, and six living young, on the thirty-first day, the average birth weight being 27.3, 32.1, and 29 grams, respectively. The remaining two rabbits delivered nine and four living young on the thirty-second day, the average birth weight being 34.9 and 40.7 grams, respectively. Three control rabbits had eleven, seven, and eight living young, on the thirty-second day, the average weight being 45, 45.9, and 46.2 grams, respectively. The last two in the group had 11 living young each on the thirty-third day, with an average weight of 45.2 and 44.7 grams, respectively.
- Group 3. The rabbit with the antepartum hemorrhage on day 18 delivered nine apparently normal living young on the twenty-ninth day, the average birth weight being 27.5 grams. The other rabbit delivered four apparently normal living young on the thirty-second day, with an average birth weight of 58.5 grams (55.4 to 64.4 grams).

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified