di-p-tolyl(2,4,6-trimethylbenzoyl)phosphine oxide

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study planned

Justification for type of information:

TESTING PROPOSAL ON VERTEBRATE ANIMALS
[Please provide information for all of the points below. The information should be specific to the endpoint for which testing is proposed. Note that for testing proposals addressing testing on vertebrate animals under the REACH Regulation this document will be published on the ECHA website along with the third party consultation on the testing proposal(s).]

NON-CONFIDENTIAL NAME OF SUBSTANCE:
- Name of the substance on which testing is proposed to be carried out
substance name: (di-p-tolylphosphoryl)(mesityl)methanone
CAS number: 270586-78-2
- Name of the substance for which the testing proposal will be used [if different from tested substance]
substance name: (di-p-tolylphosphoryl)(mesityl)methanone
CAS number: 270586-78-2

CONSIDERATIONS THAT THE GENERAL ADAPTATION POSSIBILITIES OF ANNEX XI OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION [please address all points below]:
- Available GLP studies
not available
- Available non-GLP studies
not available
- Historical human/control data
not available
- (Q)SAR
not available
- In vitro methods
not available
- Weight of evidence
not available
- Grouping and read-across
not available
- Substance-tailored exposure driven testing [if applicable]
not available
- Approaches in addition to above [if applicable]
not available
- Other reasons [if applicable]
not available

CONSIDERATIONS THAT THE SPECIFIC ADAPTATION POSSIBILITIES OF ANNEXES VI TO X (AND COLUMN 2 THEREOF) OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION:
- [free text] not available

FURTHER INFORMATION ON TESTING PROPOSAL IN ADDITION TO INFORMATION PROVIDED IN THE MATERIALS AND METHODS SECTION:
- Details on study design / methodology proposed [if relevant]
Study plan: Prenatal Developmental Toxicity Study according OECD TG 414
on (di-p-tolylphosphoryl)(mesityl)methanone
The test item(di-p-tolylphosphoryl)(mesityl)methanone in the vehicle (olive oil), will be administered by gavage once daily to Wistar female rats from day 5 to day 19 post-mating. Three groups will receive the test item at dose-levels of 100, 350 or 700 mg/kg bw/day. A concurrent vehicle control group receives the vehicle (olive oil) on a comparable regiment and in the same volume of 2 mL/kg bw. Each group will consist of at least 22 females with confirmed mating.
All females will be observed twice daily for mortality and morbidity and for signs of toxicity following dose administration. Body weights and food consumption will be recorded at three-day intervals and on the day of scheduled humane killing.
On day 20 post-mating, the dams will be sacrificed and subjected to a macroscopic examination and enumeration of corpora lutea. The weight of the thyroid gland, histopathological assessment of the thyroid gland, and assay of serum concentration of thyroxin (T4), triiodothyronine (T3) and thyroid stimulating hormone (TSH) will be done in dams to observe pathological changes in thyroid function.
Gravid uteri will be weighed and uteri content examined to record implantation sites, early and late resorptions, dead and live fetuses. The fetuses will be weighed, sexed with measurement of anogenital distance (AGD) and submitted to external examination. Half of the fetuses from each litter will be subjected to a detailed examination of soft tissue by serial sectioning after fixation in Bouin’s solution while the other half will undergo detailed skeletal examination following staining of bone with Alizarin red.

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

[bis(4-methylphenyl)phosphoroso](2,4,6-trimethylphenyl)methanone

EC Number:

884-585-5

Cas Number:

270586-78-2

Molecular formula:

C24H25O2P

IUPAC Name:

[bis(4-methylphenyl)phosphoroso](2,4,6-trimethylphenyl)methanone

Test animals

Species:

rat

Strain:

Wistar