tris[3-bromo-2,2-bis(bromomethyl)propyl] phosphate

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and appropriate guidelines

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: Annex V. B7

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Principles of method if other than guideline:

not relevant

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

413-060-1

EC Name:

-

Cas Number:

19186-97-1

Molecular formula:

C15 H24 O4 P Br9

IUPAC Name:

tris[3-bromo-2,2-bis(bromomethyl)propyl] phosphate

Constituent 2

Reference substance name:

4130601

IUPAC Name:

4130601

Details on test material:

Identity: PB-370
Reference: #E8200-58
Description: Fine white powder
Storage: Room temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

30 male and 30 female Sprague-Dawley rats were received from Charles River Labs, Portage, Michigan.
Age: 5 weeks upon receipt.
Housed individually in stainless steel cages.
Fluorescent light/dark cycle of 12 hr/12 hr
Temperature: 68-73 Deg F
RH: 26-95%
Diet: Purina Certified Rodent Chow 5002 offered ad libitum
Domestic water supply, untreated with additional HCL or chlorine was provided via an automatic watering system.

Administration / exposure

Route of administration:

oral: feed

Vehicle:

corn oil

Details on oral exposure:

See attached document on diet preparation and administration

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

See attached document on analytical verification of concentrations

Duration of treatment / exposure:

Test duration: 28 days

Frequency of treatment:

Dosing regime: once daily, 7 days/week

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 4000, 8000, 20000 ppm
Basis:
nominal in diet

No. of animals per sex per dose:

Four groups of rats (5 per sex per group)

Control animals:

yes

Details on study design:

See attached document on materials and methods

Positive control:

Yes, See attached document on materials and methods

Examinations

Observations and examinations performed and frequency:

See attached document on materials and methods

Sacrifice and pathology:

See attached document on materials and methods

Other examinations:

See attached document on materials and methods

Statistics:

See attached document on materials and methods + illustration 1

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

effects observed, treatment-related

Description (incidence and severity):

not attributed to the administration of the test material (see document on results)

Clinical biochemistry findings:

effects observed, treatment-related

Description (incidence and severity):

not attributed to the administration of the test material (see document on results)

Urinalysis findings:

not specified

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Details on results:

See attached document on results

Effect levels

Dose descriptor:

NOEL

Effect level:

20 000 ppm

Sex:

male/female

Basis for effect level:

other: corresponding with an actual consumption of 1361-1959 mg/kg/day (males) and 1691-2081 mg/kg/day (females))

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Under the conditions of the study the No Observable Effect Level (NOEL) was 20000 ppm, corresponding with an actual consumption of 1361-1959 mg/kg/day (males) and 1691-2081 mg/kg/day (females))

Executive summary:

Four groups of Charles River Sprague-Dawley CD rats (5 per sex per group) were administrated graded doses of PB-370 in the diet for 28 consecutive days. The dosage levels were 0, 4000, 8000 or 20000 ppm. Clinical signs were recorded daily. Body weights and food consumption were recorded weekly. Blood was collected prior to terminal sacrifice for hematology and clinical chemistry determinations. A complete necropsy was performed on study day 28 and selected tissues were saved, weighed and evaluated for histopathologic lesions.

There were no deaths during the study. there were no treatment related clinical signs noted in any animal. Body weights, overall body weight gains and food consumption were not statistically different among treated groups when compared to controls.

There were no haematology or clinical chemistry parameter differences that were attributed to the administration of the test material. There were no statistically significant differences in organ weights or organ:brain weight ratios when comparing treated animals to control animals. There were no compound related macroscopic or microscopic observations noted during histopathological evaluation. All changes observed were related to spontaneous disease or were an artifact. Their incidence and sevirity were typical of rats of this age and strain.

Under the conditions of the study the No Observable Effect Level (NOEL) was 20000 ppm, corresponding with an actual consumption of 1361-1959 mg/kg/day (males) and 1691-2081 mg/kg/day (females))