2,4,8,10-tetra(tert-butyl)-6-hydroxy-12H-dibenzo[d,g][1,3,2]dioxaphosphocin 6-oxide, sodium salt

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented and reported study fully adequate for assessment. The study was conducted according to internationally accepted technical guidelines and in compliance with GLP in a recognized contract research organization.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

of 1996

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2,4,8,10-tetra(tert-butyl)-6-hydroxy-12H-dibenzo[d,g][1,3,2]dioxaphosphocin 6-oxide, sodium salt

EC Number:

286-344-4

EC Name:

2,4,8,10-tetra(tert-butyl)-6-hydroxy-12H-dibenzo[d,g][1,3,2]dioxaphosphocin 6-oxide, sodium salt

Cas Number:

85209-91-2

Molecular formula:

C29H43O4P.Na

IUPAC Name:

sodium 5,7,13,15-tetra-tert-butyl-10-oxo-9,11-dioxa-10λ⁵-phosphatricyclo[10.4.0.0³,⁸]hexadeca-1(12),3,5,7,13,15-hexaen-10-olate

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Rats, Sprague Dawley origin (Hsd: Sprague-Dawley (CD))
- Source: Harlan U.K. Ltd., Bicester, Oxon, England
- Age at study start (day of dosing): 5 to 7 weeks.
- Weight at start (day of dosing): minimum 118 g, maximum 141 g.
- Fasting period: Overnight prior to dosing, until ca. 4 hours post administration.
- Housing: In groups of 3 by sex in metal cages with wire mesh floors.
- Diet: standard rodent diet (Special Diet Services RM1(E) SQC expanded pellet), ad libitum
- Drinking water : drinking water ad libitum
- Acclimation period: min. 5 days before dosing.

Routine analysis of the batch of diet used, water and chew blocks did not provide evidence of contamination that might have prejudiced the study.

ENVIRONMENTAL CONDITIONS

- Temperature (°C): 22 ± 3°C
- Relative Humidity (%): 40 to 70%
- Photoperiod (artificial lighting): 12 hrs day / 12 hrs night

There were no deviations from these ranges, which compromised the quality, integrity or outcome of the study.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

methylcellulose

Remarks:

1% w/v acqueous preparation

Details on oral exposure:

DOSE FORMULATION AND DOSE VOLUME:

- Concentration of test material in vehicle: 200 mg/mL
- Amount (dose volume by gavage): 10 mL/kg bw

Preparation of the test material on the day of dosing.

ACUTE TOXIC CLASS METHOD - Rationale for the selection of the starting dose:
The starting dose was 2000 mg/kg bw., conduction not reported.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 females
3 males

Control animals:

no

Details on study design:

- Duration of observation period: 14 days after dosing (day 1)
- Frequency of observations and weighing: observation of clinical signs after dosing, at frequent intervals of this day 1, day 2-14 twice daily,
day 15 in the morning;
weighing day 1 (prior to dosing), 8 and 15
- Necropsy performed: yes
- other examinations performed: macroscopic pathology

Statistics:

Not applicable, as there were no deaths and only one dose group.

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No deaths at 2000 mg/kg bw

Effect levels 2

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no deaths at 2000 mg/kg bw

Mortality:

Dose level Mortality
2000 mg/kg 0/3 (f)
2000 mg/kg 0/3 (m)

Clinical signs:

other: Piloerection and loose faeces were seen in all animals from Day 1; females approximately 1-2 hours post dose, males approximately 3 hours post dose. Hunched posture in all females from Day 1(from approximately 3 hours post dose). Recovery of rats, as judg

Gross pathology:

No abnormalities were revealed at the macroscopic examination at study termination on Day 15.

Applicant's summary and conclusion

Interpretation of results:

other: LD50 > 2000 mg/kg

Conclusions:

No labelling regarding acute oral toxicity according to Regulation (EC) No 1272/2008 is required.