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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Endpoint:
two-generation reproductive toxicity
Remarks:
based on test type (migrated information)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Limited study summary. Not GLP.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1986

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The Sprague-Dawley rats were used in this fertility and reproductive study. The test substance was administered into dorsal region by subcutaneous route. 10 males and 20 females were treated 60 and 14 days, respectively, before mating with each dose of drug; furthermore females only received the treatment from the first day of pregnancy until the weaning of pups (day 23 after delivery).
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
nonasodium 2-({6-[(2-carboxylato-4-hydroxy-6-{[6-hydroxy-5-(sulfonatoamino)-4-(sulfonatooxy)-2-[(sulfonatooxy)methyl]oxan-3-yl]oxy}-5-(sulfonatooxy)oxan-3-yl)oxy]-4-hydroxy-5-(sulfonatoamino)-2-[(sulfonatooxy)methyl]oxan-3-yl}oxy)-4-hydroxy-3-(sulfonatooxy)-3,4-dihydro-2H-pyran-6-carboxylate
EC Number:
700-834-1
Cas Number:
9041-08-1
Molecular formula:
not applicable (UVCB substance)
IUPAC Name:
nonasodium 2-({6-[(2-carboxylato-4-hydroxy-6-{[6-hydroxy-5-(sulfonatoamino)-4-(sulfonatooxy)-2-[(sulfonatooxy)methyl]oxan-3-yl]oxy}-5-(sulfonatooxy)oxan-3-yl)oxy]-4-hydroxy-5-(sulfonatoamino)-2-[(sulfonatooxy)methyl]oxan-3-yl}oxy)-4-hydroxy-3-(sulfonatooxy)-3,4-dihydro-2H-pyran-6-carboxylate
Details on test material:
Batch No.: not specified
Purity: not specified

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: Female and male 8 weeks of age
- Weight at study initiation: Female and male weighing 200±10 g
- Housing: The animals were housed in Makrolon cages in an air-conditioned room.
- Diet (e.g. ad libitum): Females received pelletted dry diet Altromin MT and males diet Altromin R.
- Water (e.g. ad libitum): Tap water was available ad libitum.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-23°C
- Humidity (%): 55-60%
- Air changes (per hr): Ventilation was 12 times/h
- Photoperiod (hrs dark / hrs light): Lighting schedule was 12:12 light/dark (from 7:00 a.m. to 7:00 p.m.)

No additional data

Administration / exposure

Route of administration:
subcutaneous
Vehicle:
physiological saline
Details on exposure:
The test substance dissolved in physiological solution and administered by s.c. route at 1, 5, 10 mg/kg/d at a volume of 5 mL/kg into the dorsal region.
Details on mating procedure:
- M/F ratio per cage: 1/3
- Length of cohabitation: one night
- Proof of pregnancy: sperm in vaginal smear referred to as day 1 of pregnancy

No additional data
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
10 males and 20 females were treated 60 and 14 days, respectively, before mating with each dose of drug; furthermore females only received the treatment from the first day of pregnancy until the weaning of pups (day 23 after delivery).
Frequency of treatment:
Once daily
Details on study schedule:
- F1 parental animals not mated until [10] weeks after selected from the F1 litters.

No additional data
Doses / concentrations
Remarks:
Doses / Concentrations:
1, 5, 10 mg/kg/d
Basis:
actual ingested
No. of animals per sex per dose:
10 males and 20 females
Control animals:
yes, concurrent vehicle
Details on study design:
None stated
Positive control:
None stated

Examinations

Parental animals: Observations and examinations:
None stated
Oestrous cyclicity (parental animals):
None stated
Sperm parameters (parental animals):
None stated
Litter observations:
None stated
Postmortem examinations (parental animals):
In each dose group half of the females were sacrificed on day 20 of pregnancy, the remaining pregnant animals were allowed to deliver. On sacrifice of pregnant rats, uterus, dead or viable fetuses and resorptions were observed; visceral and skeletal exam of fetuses was carried out.
Postmortem examinations (offspring):
After weaning, 20 females were randomly chosen and mated with non-consanguineous males (up to 10 weeks of age).
On day 20 of pregnancy, half of the females of this progeny, were necropsied and uterus and fetuses were examined for implantation sites, including viable, dead and/or resorbed fetuses.
On 10 females of each group dose was recorded the fertility and on day 20 of gestation the animals were sacrificed.
Statistics:
The results were statistically analyzed by Student's t-test for independent samples.
Reproductive indices:
None stated
Offspring viability indices:
None stated

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Organ weight findings including organ / body weight ratios:
not specified
Histopathological findings: non-neoplastic:
not specified
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
no effects observed

Details on results (P0)

The test substance up to 10 mg/kg by s.c. route did not influence the fertility of parents.

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
>= 10 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
not specified
Basis for effect level:
other: The test substance up to 10 mg/kg by s.c. route did not influence the fertility of parents.

Results: F1 generation

General toxicity (F1)

Clinical signs:
no effects observed
Mortality / viability:
no mortality observed
Body weight and weight changes:
no effects observed
Sexual maturation:
no effects observed
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
no effects observed
Histopathological findings:
not specified

Details on results (F1)

The average numbers of viable fetuses, implantation sites, anomalies and weight of fetuses were in good agreement with the control group.

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The studies on the fertility and on the reproductive performance in rats, carried out on F0, F1 and F2 progenies, showed that the test substance up to 10 mg/kg by s.c. route did not influence the fertility of parents and the pregnancy of dams; moreover in this study no effects on fetal and peri- and postnatal development of progeny were observed.