6-aminopenicillanic acid

Toxicity to reproduction

Administrative data

Endpoint:

one-generation reproductive toxicity

Remarks:

based on test type (migrated information)

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: A reasonable level of reporting, conducted to a good scientific standard.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1964

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Sixty female albino CD rats were divided into groups of 20 as control, 200 or 400 mg/kg bw/day of amipicillin anhydrate. The test material was incorporated into dry powdered food and adminsitered to male rats for four weeks prior to mating and to female rats, from two weeks prior to mating. The dose was gradually administered in food to acclimatise the animals to the bitter taste. Females were mated with males on a one to one basis. Females were dosed up to weaning for a total of at least 15 weeks. Pups were sacrificed periodically up to 1 month post weaning and examined for abnormalities.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ampicillin, anhydrous

IUPAC Name:

Ampicillin, anhydrous

Details on test material:

- Name of test material : Ampicillin, anhydrous (R-12, 101-5)

Test animals

Species:

rat

Strain:

CD-1

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Housing: Housed individually
- Diet : ad libitum
- Water : ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature : 74-76 °F
- Humidity (%): 46-48%

Administration / exposure

Route of administration:

oral: feed

Vehicle:

not specified

Details on exposure:

DIET PREPARATION
- Rate of preparation of diet (frequency): Fresh diet was prepared weekly

Details on mating procedure:

- M/F ratio per cage: 1:1
- Length of cohabitation: Sunday to Wednesday
- Proof of pregnancy: vaginal plug
- Further matings after two unsuccessful attempts: yes, females whose mating was not successful in the first period, were mated again the same way the following weeks until all became pregnant.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

At least 15 weeks

Frequency of treatment:

Daily

Doses / concentrations

Remarks:

Doses / Concentrations:
Control (0), 200 and 400 mg/kg bw/day
Basis:
nominal in diet

No. of animals per sex per dose:

20 females per dosing group.

Control animals:

yes, plain diet

Examinations

Parental animals: Observations and examinations:

CAGE SIDE OBSERVATIONS: Yes

BODY WEIGHT: Yes

Litter observations:

STANDARDISATION OF LITTERS
- Performed at postpartum
- If yes, maximum of 6 pups/litter 3 of each sex/litter as near as possible); excess pups were killed and discarded.

PARAMETERS EXAMINED
The following parameters were examined in F1 offspring:
number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, weight gain, physical abnormalities

GROSS EXAMINATION OF DEAD PUPS:
possible cause of death was determined for pups born or found dead

Postmortem examinations (offspring):

SACRIFICE
Animals not selected for further study were sacrificed by chloroform inhalation at parturition. Two were placed in alcohol, and the others in formalin. The pups placed in alcohol were processed by a modified Dawson's method with Alizarin red S staining for the study of bone malformations. Mortality of the pups was recorded twice, up to the first day and at weaning time. At weaning, pups were again examined carefully for gross malformations, weighed and measured. Two of each cage were left alive, the others were killed and the internal organs were examined. The surviving rats were killed one month later and checked again for gross malformations.

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

no effects observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Organ weight findings including organ / body weight ratios:

not examined

Histopathological findings: non-neoplastic:

not examined

Other effects:

not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

not examined

Reproductive function: sperm measures:

not examined

Reproductive performance:

no effects observed

Details on results (P0)

CLINICAL SIGNS AND MORTALITY (PARENTAL ANIMALS) All animals appeared normal during the course of the test.

BODY WEIGHT AND FOOD CONSUMPTION (PARENTAL ANIMALS) The weights of the females did not vary from the controls

REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS) All the rats became pregnant in the first three mating cycles

Effect levels (P0)

Dose descriptor:

NOAEL

Effect level:

> 400 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: see 'Remark'

Results: F1 generation

General toxicity (F1)

Clinical signs:

not examined

Mortality / viability:

no mortality observed

Body weight and weight changes:

no effects observed

Sexual maturation:

not examined

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

no effects observed

Histopathological findings:

not specified

Details on results (F1)

VIABILITY (OFFSPRING) No differences in litter size and ratio of males to females in the treatment groups compared to the control group.

BODY WEIGHT (OFFSPRING) Weight and length of the pups were unaffected

GROSS PATHOLOGY (OFFSPRING) No morphological abnormalities occured during the course of the study.

Effect levels (F1)

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

> 400 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: see 'Remark'

Overall reproductive toxicity

Reproductive effects observed:

not specified

Any other information on results incl. tables

Prenatal Toxicity of R-12.101-5 in Rats Oral Administration – Summary

 

Group	No. of females mated	No. of females with litter	Average gestation period (days)	No. of pups			Average No. of pups/litter	No. of abnormalities	Mortality
				Male	Female	Total			Within 24 hours	Up to weaning
Control	15	13	22.2	70	78	148	11.4	0	5 (1 eaten)	3
200 mg/kg/day	20	20	21.8	111	126	237	11.9	0	8	2
400 mg/kg/day	20	18	21.7	113	104	217	12.0	0	7 (3 eaten)	2 (1 accident)

Applicant's summary and conclusion

Conclusions:

No effects were noted in a one litter prenatal toxicity study in rats dosed with either 200 or 400 mg/kg bw/day of ampicillin anhydrous.