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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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well-documented, GLP-compliant, according to OECD422 in rat.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
Deviations:
no
Principles of method if other than guideline:
other: combined repeated dose and reproduction / developmental screening
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): Granular Triple Superphosphate (GTSP)
- Substance type: Light brown to black granules
- Physical state: Solid
- Analytical purity: Treated as 100% pure
- Purity test date: Not indicated
- Lot/batch No.: ERC 20.12.2001/02
- Expiration date of the lot/batch: Not indicated.
- Stability under test conditions: Not indicated.
- Storage condition of test material: Room temperature (test formulations in the freezer, -20°C)
- Composition of test material, percentage of components: tested batched contained 45.43% P2O5 equivalent


Test animals

Species:
rat
Strain:
Sprague-Dawley
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Limited, Margate, Kent, England.
- Age at study initiation: 9-10 weeks
- Weight at study initiation: 297 to 365 g for males and 194 to 251 g for females
- Fasting period before study: not applicable
- Housing:Unless paired for mating, the animals were singly housed in RB3 modified cages consisiting of high density polypropylene bodies with lids and floors of stainless steel grid. These cages were suspended in batteries over trays lined with absorbent paper. RB3 modified cages were used
throughout the study with the exception of reproductive subgroup females from Day 17 after mating, where RB3 solid-bottomed cages were used.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 12 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23°C
- Humidity (%): 40-70%, , on one occasion during the acclimatization period relative humidity was recorded as 20% and was re-established within
24 hours.
- Air changes (per hr): approximately 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 19 December 2001 To: 19 February 2002

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:
The formulation for Group 4 (150 mg/mL) was mixed by adding the required volume of vehicle (water purified by reverse osmosis) to the required
weight of GTSP and magnetically stirring for up to 1 hour until a visibly homogenous brown suspension was formed. Formulation for Groups 3 and 2
were prepared by direct dilution of this suspension.

VEHICLE
- Concentration in vehicle: 25 - 75 - 150 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg
Details on analytical verification of doses or concentrations:
See Section 7.8.1.
Details on mating procedure:
See Section 7.8.1.
Duration of treatment / exposure:
See Section 7.8.1.
Frequency of treatment:
See Section 7.8.1.
Duration of test:
See Section 7.8.1.
Doses / concentrations
Remarks:
Doses / Concentrations:
250, 750, 1500 mg/kg b.w.
Basis:
actual ingested
No. of animals per sex per dose:
See Section 7.8.1.
Control animals:
yes, concurrent vehicle
Details on study design:
See Section 7.8.1.

Examinations

Maternal examinations:
See Section 7.8.1.
Ovaries and uterine content:
See Section 7.8.1.
Fetal examinations:
See Section 7.8.1.
Statistics:
See Section 7.8.1.
Indices:
See Section 7.8.1.
Historical control data:
See Section 7.8.1.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:no effects. Remark: See Section 7.8.1.

Details on maternal toxic effects:
See Section 7.8.1.

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
750 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
other: other:

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects. Remark: See Section 7.8.1.

Details on embryotoxic / teratogenic effects:
See Section 7.8.1.

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

See Section 7.8.1.

Applicant's summary and conclusion

Conclusions:
NOAEL: 750 mg/kg/day for reproduction/developmental toxicity based on body weights of offspring.
NOAEL: < 250 mg/kg/day for general toxicity, since the local (mostly slight to mild) stomach effects at 250 mg/kg are considered due to an
irritant rather than toxic effect of the test substance formulations and kidney effects.