6,6'-[(3,3'-di-tert-butyl-5,5'-dimethoxybiphenyl-2,2'-diyl)bis(oxy)]bis(dibenzo[d,f][1,3,2]dioxaphosphepine)

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Remarks:

combined repeated dose and reproduction / developmental screening

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline and GLP Study, very well documented

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)

GLP compliance:

yes (incl. QA statement)

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

9-[(3,3'-di-tert-butyl-2'-{8,10-dioxa-9-phosphatricyclo[9.4.0.0²,⁷]pentadeca-1(11),2(7),3,5,12,14-hexaen-9-yloxy}-5,5'-dimethoxy-[1,1'-biphenyl]-2-yl)oxy]-8,10-dioxa-9-phosphatricyclo[9.4.0.0²,⁷]pentadeca-1(11),2(7),3,5,12,14-hexaene

EC Number:

700-178-6

Cas Number:

121627-17-6

Molecular formula:

C46H44O8P2

IUPAC Name:

9-[(3,3'-di-tert-butyl-2'-{8,10-dioxa-9-phosphatricyclo[9.4.0.0²,⁷]pentadeca-1(11),2(7),3,5,12,14-hexaen-9-yloxy}-5,5'-dimethoxy-[1,1'-biphenyl]-2-yl)oxy]-8,10-dioxa-9-phosphatricyclo[9.4.0.0²,⁷]pentadeca-1(11),2(7),3,5,12,14-hexaene

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

up to 54 d

Frequency of treatment:

1 per day

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
300 mg/kg/day
Basis:
nominal in diet

Doses / concentrations 2

Remarks:

Doses / Concentrations:
100 mg/kg/day
Basis:
nominal in diet

Doses / concentrations 3

Remarks:

Doses / Concentrations:
1000 mg/kg/day
Basis:
nominal in diet

No. of animals per sex per dose:

10

Control animals:

yes

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:

no effects observed

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Behaviour (functional findings):

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: see 'Remark'

2

Dose descriptor:

NOEL

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No treatment-related effects were observed for reproduction or for developmental effects in the offspring.

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Results and observations

Mortality. There were no unscheduled deaths during the study.

Clinical Observations. No toxicologically significant signs of toxicity were detected throughout the study.

Behavioural Assessment. There were no treatment-related changes in the behavioural parameters measured.

Functional Performance Tests. There were no toxicologically significant changes in functional performance.

Sensory Reactivity Assessments. There were no treatment-related changes in sensory reactivity.

Bodyweight. No adverse effects on bodyweight development were detected for treated animals when compared to controls.

Food Consumption. No adverse effects on food consumption or food efficiency were detected for treated animals when compared to controls.

Haematology. No toxicologically significant effects were detected in the haematological parameters measured.

Blood Chemistry. No toxicologically significant effects were detected in the blood chemical parameters measured.

Reproductive Performance:

Mating and Fertility. There were no treatment-related effects on mating or conception rates.

Gestation Length. There were no treatment-related effects detected in gestation length.

Litter Responses: Offspring Litter Size and Viability. Litter size at birth and subsequently at Days 1 and 4 post partum were comparable to controls.

Offspring Growth and Development. Offspring bodyweight gain and litter weights at birth and subsequently on Day 1 and Day 4 post partum were comparable to controls.

Organ Weights. No toxicologically significant effects were detected in the organ weights measured.

Necropsy. No toxicologically significant macroscopic abnormalities were detected.

Histopathology. No treatment-related changes were detected.

Conclusion.

The oral administration of L17 to rats by gavage, at dose levels of 1000, 300 and 100 mg/kg/day, resulted in treatment-related effects in males from all treatment groups and in females treated with 1000 and 300 mg/kg/day. These effects were considered not to represent an adverse health effect, as such the 'No Observed Adverse Effect Level' (NOAEL) for systemic toxicity was considered to be 1000 mg/kg/day. No treatment-related effects were observed for reproduction or for developmental effects in the offspring, therefore, the ‘No Observed Effect Level’ (NOEL) for reproductive, developmental and teratogenicity toxicity was considered to be 1000 mg/kg/day.