3,9-bis[2,4-bis(1-methyl-1-phenylethyl)phenoxy]-2,4,8,10-tetraoxa-3,9-diphosphaspiro[5.5]undecane;bis(2,4-dicumylphenyl) neopentyl diphosphite

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP Compliance, not OECD guideline

Data source

Reference

Reference Type:

other: Body responsible for the test

Title:

Unnamed

Year:

2015

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Directive 92/69 EEC, B. 7

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

421-920-2

EC Name:

-

Cas Number:

154862-43-8

Molecular formula:

C53-H58-O6-P2

IUPAC Name:

3,9-bis[2,4-bis(2-phenylpropan-2-yl)phenoxy]-2,4,8,10-tetraoxa-3,9-diphosphaspiro[5.5]undecane

Test animals

Species:

rat

Strain:

Sprague-Dawley

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

corn oil

Details on oral exposure:

Method of administration: gavage

Duration of treatment / exposure:

Test duration: 28 days

Frequency of treatment:

Dosing regime: 7 days/week

No. of animals per sex per dose:

Male: 10 animals at 0 mg/kg bw/day
Male: 5 animals at 50 mg/kg bw/day
Male: 5 animals at 200 mg/kg bw/day
Male: 10 animals at 500 mg/kg bw/day
Female: 10 animals at 0 mg/kg bw/day
Female: 5 animals at 50 mg/kg bw/day
Female: 5 animals at 200 mg/kg bw/day
Female: 10 animals at 500 mg/kg bw/day

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Description (incidence and severity):

There were no test article-related clinical signs noted in any dose group.

Mortality:

no mortality observed

Description (incidence):

All animals survived the scheduled treatment period.

Body weight and weight changes:

no effects observed

Description (incidence and severity):

There was no effect on body weights.

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

Food consumption was uneffected by treatment with test article.

Food efficiency:

not specified

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

not specified

Ophthalmological findings:

effects observed, non-treatment-related

Description (incidence and severity):

Ophthalmologic findings were noted in a small proportion of animals from all groups. They included corneal opacity and degeneration of the eyes. These findings occured at similar incidences in the control and treated groups at the end of the treatment period. Therefore, they are considered to be unrelated to treatment with test article.

Haematological findings:

effects observed, non-treatment-related

Description (incidence and severity):

There were no treatment related effects on hematology, clinical biochemistry and urinalysis data at termination of the treatment nor at the end of the treatment free recovery period which could be considered of toxicological significance.
However a few minor findings with statistical significance were recorded between the control and treated rats of group 4 at termination of the treatment and/or recovery period. The toxicological relevance of these statistical findings is considered to be doubtful.

Clinical biochemistry findings:

effects observed, non-treatment-related

Description (incidence and severity):

There were no treatment related effects on hematology, clinical biochemistry and urinalysis data at termination of the treatment nor at the end of the treatment free recovery period which could be considered of toxicological significance.
However a few minor findings with statistical significance were recorded between the control and treated rats of group 4 at termination of the treatment and/or recovery period. The toxicological relevance of these statistical findings is considered to be doubtful.

Urinalysis findings:

effects observed, non-treatment-related

Description (incidence and severity):

There were no treatment related effects on hematology, clinical biochemistry and urinalysis data at termination of the treatment nor at the end of the treatment free recovery period which could be considered of toxicological significance.
However a few minor findings with statistical significance were recorded between the control and treated rats of group 4 at termination of the treatment and/or recovery period. The toxicological relevance of these statistical findings is considered to be doubtful.

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Description (incidence and severity):

Organ weights were uneffected by treatment with test article.

Gross pathological findings:

effects observed, non-treatment-related

Description (incidence and severity):

Most macroscopic findings recorded were unremarkable and within the range of spontaneous alterations which may be seen in rats of this age and strain.

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

effects observed, non-treatment-related

Description (incidence and severity):

Chiefly minor degrees of hepatocellular vacuolization representing slight hepatic lipidosis, were noted in the liver of both control and treated rats at both sacrifices. This was considered to be due to the vehicle, corn oil.

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

200 mg/kg bw/day (nominal)

Basis for effect level:

other: original NCD unit is mg/kg/day.

2

Dose descriptor:

NOEL

Effect level:

200 mg/kg bw/day (nominal)

Basis for effect level:

other: original NCD unit is mg/kg/day.

Target system / organ toxicity

Critical effects observed:

not specified