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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
no data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study similar/equivalent to OECD Guideline 414 with acceptable restrictions.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
grey literature
Title:
Unnamed
Year:
1975
Report Date:
1975

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
yes
Remarks:
: CAS# and purity of test substance not provided; no mention of acclimization, minimal data on environmental conditions were included, no data on macroscopic examination of dams was provided.
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): FDA 73-2; Monosodium phosphate, anhydrous
- Physical state: fine white powder

Test animals

Species:
mouse
Strain:
CD-1
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: adult
- Weight at study initiation: average body weight on day 0 ranged from 29-31 g
- Fasting period before study: no data
- Housing: gang-housed in disposable plastic cages
- Diet: ad libitum
- Water: tap water ad libitum
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): controlled
- Humidity (%): controlled
- Air changes (per hr): no data .
- Photoperiod (hrs dark / hrs light): no data


IN-LIFE DATES: From: no data To: no data

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: Administered as a water suspension (10 mL per kg of body weight)



Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
- Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: One male was not permitted to impregnate more than one female per group
- Length of cohabitation: no data.
- Further matings after two unsuccessful attempts: no data
- Verification of same strain and source of both sexes: no data
- Proof of pregnancy: pesence of a vaginal plug was referred to as day 0 of pregnancy
Duration of treatment / exposure:
10 days (Females were dosed beginning on day 6 through day 15 of gestation)
Frequency of treatment:
Daily
Duration of test:
17 days ( Day 17 of gestation)
Doses / concentrations
Remarks:
Doses / Concentrations:
3.7, 17.2, 79.7, and 370.0 mg/kg
Basis:
actual ingested
No. of animals per sex per dose:
25 females per test substance dose group, 27 animals in the positive control group
Control animals:
yes, sham-exposed
Details on study design:
The study also included a positive control (Aspirin) at 150 mg/kg

Examinations

Maternal examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Observed daily for appearance and behavior with particular attention to food consumption and weight, in order to rule out any abnormalities which may have occurred as a result of anorexic effects in the pregnant female animal.


BODY WEIGHT: Yes
- Time schedule for examinations: Recorded on days 0, 6, 11, 15 and 17 of gestation.


POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 17
- Organs examined: urogenital tract of each dam was examined in detail for anatomical normality.


OTHER: Daily room temperature and humidity were recorded.
Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No data
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of resorptions: Yes
- Other: The sex, number of live and dead fetuses and the body weights of the live pups were recorded.
Fetal examinations:
- External examinations: Yes: all per litter
- Soft tissue examinations: Yes: 1/3 per litter underwent detailed visceral examinations employing the Wilson technique.
- Skeletal examinations: Yes: remaining 2/3 were cleared in potassium hydroxide (KOH), stained with alizarin red S dye and examined for skeletal defects.
- Head examinations: No data
Statistics:
no data

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:no effects

Details on maternal toxic effects:
No appreciable effects were identified on the average body weight of any of the dose groups.

No deleterious observational effects were noted.

No effects were identified in regard to the number of pregnancies, corpora lutea, live litters, implant sites, or resorptions between the test substance dose groups and the sham control treated group.

Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOAEL
Effect level:
>= 370 mg/kg bw/day
Basis for effect level:
other: developmental toxicity
Dose descriptor:
NOAEL
Effect level:
>= 370 mg/kg bw/day
Basis for effect level:
other: maternal toxicity

Results (fetuses)

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

Details on embryotoxic / teratogenic effects:
No effects were identified in regard to the number of live fetuses, dead fetuses or the average fetal weight between the test substance dose groups and the sham control treated group.
The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring spontaneously in the sham-treated controls.

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The administration of up to 370 mg/kg (body weight) of the test material to pregnant mice for 10 consecutive days had no clearly discernible effect on nidation or on maternal or fetal survival. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring spontaneously in the sham-treated controls.