Reaction mass of phosphonic acid, methyl-, bis[(5-ethyl-2-methyl-2,2-dioxido-1,3,2-dioxaphosphorinan-5-yl)methyl] ester with (5-ethyl-2-methyl-2-oxido-1,3,2-dioxaphosphorinan-5-yl)methyl methyl methylphosphonate

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of phosphonic acid, methyl-, bis[(5-ethyl-2-methyl-2,2-dioxido-1,3,2-dioxaphosphorinan-5-yl)methyl] ester with (5-ethyl-2-methyl-2-oxido-1,3,2-dioxaphosphorinan-5-yl)methyl methyl methylphosphonate

EC Number:

915-680-2

Cas Number:

170836-68-7

Molecular formula:

not applicable for UVCB substance

IUPAC Name:

Reaction mass of phosphonic acid, methyl-, bis[(5-ethyl-2-methyl-2,2-dioxido-1,3,2-dioxaphosphorinan-5-yl)methyl] ester with (5-ethyl-2-methyl-2-oxido-1,3,2-dioxaphosphorinan-5-yl)methyl methyl methylphosphonate

Test material form:

liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

The substance was administrated by gavage to 15 male and 15 female rats per group for 90 consecutive days at dose levels of 500, 1500 and 3000 mg/kg.A fourth group of rats formed the control.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

not specified

No. of animals per sex per dose:

15

Details on study design:

Potential toxic effects were evaluated in terms of the following: Appearance and behavior, mortality, body weight, Food consumption,Efficiency of food utilization, Hematology, Clinical Chemistry, Urinalysis, Necropsy examination ( including weight of 9 organs) and Histologic examination ( of up to 25 tissues in each of the high and control groups).

Results and discussion

Results of examinations

Body weight and weight changes:

effects observed, non-treatment-related

Description (incidence and severity):

With reference to body weight, male rats from the 3 000 mg/kg group showed significantly less body weight gain than the other 3 groups at weeks 9,12 and 13.

Food consumption and compound intake (if feeding study):

effects observed, non-treatment-related

Description (incidence and severity):

Statistical analysis of food consumption values revealed that male rats from the 3 000 mg/kg group showed significantly less food consumption than the control group at week 5 and significantly less food consumption than the other 3 groups at week 7. For female rats, the following significance was observed: at week 5 the control group consumed significantly greater amounts than the other 3 groups; at week 8 the control group consumed significantly less than the 1500 and 3000 mg /kg groups and at week 12 the 1500 mg/kg group consumed significantly less than the other 3 groups. No consistent significant differences were therefore established for food consummation

Clinical biochemistry findings:

not specified

Description (incidence and severity):

Clinical chemistry determinations revealed that pre-test for lactic acid dehydrogenase were elevated for all groups and this evaluation was probably attributed to hemolysis. At 90 days, clinical chemistry values for test animals were comparable to control.

Urinalysis findings:

no effects observed

Description (incidence and severity):

Urinalysis determinations gave no evidence of any compound related effects

Behaviour (functional findings):

no effects observed

Histopathological findings: neoplastic:

effects observed, non-treatment-related

Description (incidence and severity):

Histopathological evaluation revealed the appearance of fatty degeneration and cloudy swelling of the liver in all dose levels. However, this finding was reproduced in the test animals with a somewhat greater incidence of fatty degeneration at the 1500 mg/kg level. In the 500 mg/kg dose, the degree of change was similar to the controls. In the 3 000 mg/kg dose, the incidence was moderately increased over the control, but not to the extent seen at the 1500 mg/kg dose.

Effect levels

Key result

Dose descriptor:

other: NOAC

Effect level:

ca. 3 000 other: mg/kg

Based on:

test mat.

Sex:

male/female

Basis for effect level:

behaviour (functional findings)

body weight and weight gain

clinical biochemistry

food consumption and compound intake

Target system / organ toxicity

Key result

Critical effects observed:

no

System:

other:

Applicant's summary and conclusion

Conclusions:

The findings at 1500 and 3000 mg/kg are not statistically definite and it is concluded that the substance does not produce noteworthy toxic effects by comparison between control and test animals. The NOAC is therefore considered to be 3000 mg/kg.