4,8-dicyclohexyl-6-hydroxy-2,10-dimethyl-12H-dibenzo[d,g][1,3,2]dioxaphosphocin

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1988-04-26 - 1988-05-10

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Study conducted under GLP according to EU method B.1 on the registered substance itself. The method is to be considered scientifically reasonable with negligible deficiencies and methodological variations due to the intrinsic properties of the test item, which are foreseen in the guideline.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

as published in 84/449/EWG

Deviations:

yes

Remarks:

limit dose only 2000 mg/kg

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4,8-dicyclohexyl-6-hydroxy-2,10-dimethyl-12H-dibenzo[d,g][1,3,2]dioxaphosphocin

EC Number:

277-633-6

EC Name:

4,8-dicyclohexyl-6-hydroxy-2,10-dimethyl-12H-dibenzo[d,g][1,3,2]dioxaphosphocin

Cas Number:

73912-21-7

Molecular formula:

C27H35O3P

IUPAC Name:

7,13-dicyclohexyl-5,15-dimethyl-9,11-dioxa-10-phosphatricyclo[10.4.0.0³,⁸]hexadeca-1(12),3(8),4,6,13,15-hexaen-10-ol

Test material form:

solid: flakes

Details on test material:

- Name of test material (as cited in study report): 12H-Dibenzo(d,g)(1,3,2)dioxaphosphocin, 4,8-dicyclohexyl-6-hydroxy-2,10-dimethyl
- Substance type: pure substance
- Storage condition of test material: room temperature

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: strain Bor: WISW (Spf Cpb) from Breeder Winkelmann, Borchen, Germany
- Age at study initiation: 9 weeks (males), 14 weeks (females)
- Weight at study initiation (average): 172g (males), 173g (females), weight variation < ±20% of mean value
- Fasting period before study: 16h
- Housing: in groups of five in Makrolon cages Type III on dust-free wood pellets (Ssniff, Soest/Westfalen)
- Diet (e.g. ad libitum): fixed-formula standard diet Altromin 1324 Pellets (Altromin GmbH, Lage, Germany) ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: min. 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±2°C
- Humidity (%): ca. 50±10%
- Air changes (per hr): ca. 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

400

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 20 ml/kg bw

MAXIMUM DOSE VOLUME APPLIED: 2 x 20 ml/kg bw

DOSAGE PREPARATION (if unusual): suspension

Doses:

2000 mg/kg, applied as 2 x 1000 mg/kg with a 6h interval

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: inspections twice daily (once on weekends and bank holidays), weighing prior application, after 1 week and at the end of the study
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

male

Dose descriptor:

LD0

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

On the second day after treatment one female died.

Clinical signs:

other: Beginning ca. 1h after the first application of 1000 mg/kg a slightly ruffled fur was observed on all animals. This effect was rather slight and persisted until day 5 after application. One female was on the day after application in a poor general conditi

Gross pathology:

A pathological/anatomical examination of the dead female was not possible due to cannibalism.
All sacrificed animals at the end of the study were without pathological/anatomical findings.

Applicant's summary and conclusion

Interpretation of results:

other: EU-GHS criteria not met

Conclusions:

The study was conducted under GLP according to EU method B.1 on the registered substance itself. The method is to be considered scientifically reasonable with negligible deficiencies and methodological variations due to the intrinsic properties of the test item, which are foreseen in the guideline. Hence, the results can be considered as sufficiently reliable to assess the acute oral toxicity in rats. The determined LD50 value is >2000 mg/kg bw, the LD0 ≥ 2000 mg/kg in male rats, as only one female died after gavage of 2000 mg/kg bw. The result is suitable to determine the classification of 12H-Dibenzo(d,g)(1,3,2)dioxaphosphocin, 4,8-dicyclohexyl-6-hydroxy-2,10-dimethyl. According to Directive 79/831/EWG, no classification is required. According to Regulation (EC) No. 1272/2008, the substance does not need to be classified as acute toxic cat. IV or higher.

Executive summary:

In an acute oral toxicity study under GLP according to EU method B.1, groups of fasted 9-14 weeks old Wistar Bor: WISW (SPF Cpb) rats (5/sex) were given a single oral dose of 12H-Dibenzo(d,g)(1,3,2)dioxaphosphocin, 4,8-dicyclohexyl-6-hydroxy-2,10-dimethyl (2 x 1000 mg/kg bw with 6h interval) in polyethylenglycol 400 at a limit dose of 2000 mg/kg bw and observed for 14 days.

 

Oral LD₅₀> 2000 mg/kg bw

Oral LD₀≥ 2000 mg/kg bw (males)

One female died during the test after 2 days. One hour after application, ruffled fur was observed in all animals and lasted until day 6. At the end of the test, all animals were without pathological/anatomical findings.

 

12H-Dibenzo(d,g)(1,3,2)dioxaphosphocin, 4,8-dicyclohexyl-6-hydroxy-2,10-dimethyl is of low Toxicity based on the LD₅₀ and does not need to be classified as acute toxic cat. IV or higher.