2-benzyl-4-methyl-4a,5,6,7,8,8a-hexahydro-4H-benzo[d][1,3]dioxine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 08 and 23 November, 2011

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

GLP study conducted in compliance with OECD Guideline No. 423 without any deviation. The substance is adequately identified, but details on composition are missing. Therefore validation applies with restrictions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

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:

17 December 2001.

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

regulation No. 440/2008

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

Inspected on 2010-12-07 / Signed on 2011-03-07.

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-benzyl-4-methyl-octahydro-1,3-benzodioxine

EC Number:

956-606-9

Cas Number:

1373821-23-8

Molecular formula:

C16 H22 O2

IUPAC Name:

2-benzyl-4-methyl-octahydro-1,3-benzodioxine

Test material form:

liquid

Details on test material:

- Physical state: colourless liquid.
- Storage condition of test material: fridge 6°C±3°C, dark

Specific details on test material used for the study:

Date received: 20 October 2011

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage JANVIER (53940 Le Genest St Isle, France)
- Age at study initiation: 8 - 9 weeks
- Weight at study initiation: 186 - 223 g
- Housing: housed by group of three in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid.
- Diet: foodstuff (M20, SDS), ad libitum but food was removed at D-1 and then redistributed 4 hours after the test item administration.
- Water: tap-water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-25 °C
- Humidity: 30-70%
- Air changes: approximately fifteen changes per hour.
- Photoperiod: 12 h light/12 h darkness.

IN-LIFE DATES: From 08 to 23 November, 2011.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 1.93 mL/kg bw

ADMINISTRATION OF TEST ITEM:
Animals received an effective dose of 2000 mg/kg bw of the test item, administered by gavage under a volume of 1.93 mL/kg bw using a suitable syringe graduated fitted with an oesophageal metal canula.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed 30 min, 1, 3 and 4 hours after test item administration and thereafter once daily for 14 days. Animals were weighed pretest (Day 0) and on Day 2, 7 and 14.
- Necropsy of survivors performed: Yes; Animals were killed on Day 14 and subjected to macroscopic examination.

Statistics:

None

Results and discussion

Preliminary study:

Not applicable

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 mortality occurred during the study.

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study.

Clinical signs:

other: On the first day of the test, a decrease in spontaneous activity (2/6) was noted. The animals recovered a normal activity at 24-hours post dose.

Gross pathology:

The macroscopical examination of the animals at the end of the study did not reveal treatment-related changes.

Other findings:

None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the oral LD50 for test substance is higher than 2000 mg/kg bw and the LD50 cut-off may be considered to be higher than 5000 mg/kg body in female rats. Therefore, the substance is not classified according to the annex I of the Regulation EC No. 1272/2008 (CLP) and to the GHS.

Executive summary:

In an acute oral toxicity study (limit test) performed according to OECD Guideline 423 and in compliance with GLP, 6 female Sprague Dawley rats were given a single oral (gavage) dose of test item at 2000 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination.

 

No mortality occurred during the study. No significant clinical signs related to the administration of the test item were observed. The body weight evolution of the animals remained normal throughout the study, similar between treated and control animals. The macroscopical examination of the animals at the end of the study did not reveal treatment-related changes.

 

Oral LD50 Female > 2000 mg/kg bw

Under the test conditions, the oral LD50 for test substance is higher than 2000 mg/kg bw and the LD50 cut-off may be considered to be higher than 5000 mg/kg body in female rats. Therefore, the substance is not classified according to the annex I of the Regulation EC No. 1272/2008 (CLP) and to the GHS.

This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.