Registration Dossier

Toxicological information

Developmental toxicity / teratogenicity

Currently viewing:

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)
Rationale for reliability incl. deficiencies:
other: Data taken from EU risk assessment of piperazine. Piperazine is a constituent of the test substance and therefore used as read across.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1987

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
no
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): piperazine phosphate
- The piperazine content within this salt is 42%

Test animals

Species:
rat
Strain:
Sprague-Dawley
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
no data
Duration of treatment / exposure:
Treatment during pregnancy days 6- 15
Frequency of treatment:
daily
Duration of test:
10 days
Doses / concentrations
Remarks:
Doses / Concentrations:
105, 420, 2100 mg/kg bw/day
Basis:
actual ingested
calculated as piperazine base
No. of animals per sex per dose:
24 per dose group
Control animals:
yes, concurrent no treatment

Examinations

Maternal examinations:
Clinical signs, body weights and food consumption were recorded.
Fetal examinations:
External, visceral and skeletal examinations were done.
Indices:
Pre- and post-implantation losses, litter sizes and sex ratios were examined.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Details on maternal toxic effects:
Excessive salivation, lethargy and reduction in body weight gain (day 6-15), body weight (7% at day 15) and food consumption (14% during days 6-11 and 9% days 11-15).
Pre- and post-implantation losses, litter sizes and sex ratios were unaffected by treatment.

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
420 mg/kg bw/day (actual dose received)
Basis for effect level:
other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
Lower foetal weight at highest dose (7%), but no evidence of teratogenicity.

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
2 100 mg/kg bw/day (actual dose received)
Basis for effect level:
other: teratogenicity

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
No evidence of teratogenicity was found.
Executive summary:

Female rats were treated by oral gavage of piperazine phosphate solution on pregnancy days 6 to 15, in doses 105, 420 and 2100 mg/kg bw/day calculated as piperazine base. Maternal effects were excessive salivation, lethargy and reduction in body weight gain, body weight and food consumption. Lower foetal weights were observed at highest dose, but there was no evidence of teratogenicity.