Reaction mass of 4-methylene-2-phenyltetrahydro-2H-pyran and 4-methyl-2-phenyl-3,6-dihydro-2H-pyran

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP study conducted similarly to OECD Guideline 401 with deviations: no data about purity and no certificate of analysis of test substance; bodyweight changes were not reported

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

no GLP statement; no data about purity and no certificate of analysis of test substance; bodyweight changes were not reported

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of 4-methylene-2-phenyltetrahydro-2H-pyran and 4-methyl-2-phenyl-3,6-dihydro-2H-pyran

EC Number:

943-338-2

Molecular formula:

C12H14O

IUPAC Name:

Reaction mass of 4-methylene-2-phenyltetrahydro-2H-pyran and 4-methyl-2-phenyl-3,6-dihydro-2H-pyran

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): 2-Phenyl-4-methyl dihydropyran
- Date received: 10 October 1980
- Physical state: Clear colourless liquid with a pungent odour

Please note that although the substance is stated as a mono-constituent substance 2-phenyl-4-methyl dihydropyran in the report, recent analytical data has determined the substance to be a multi-constituent (Reaction mass of 3,6-dihydro-4-methyl-2-phenyl-2H-pyran and tetrahydro-4-methylene-2-phenyl-2H-pyran). As the chemical manufacturing process has not changed since the report was written, the recent analytical information is relevant to the batch which was tested.

Test animals

Species:

rat

Strain:

other: Cpb; WU; Wistar Random

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: Young adult
- Source: Central Institute for the Breading of Laboratory Animals TNO, Zeist, The Netherlands
- Weight at study initiation: Males: 160-205 g; females: 114-162 g
- Housing: Animals were housed in groups of five in screen-bottomed stainless steel cages.
- Fasting period before study: Overnight
- Diet: Stock diet, ad libitum
- Water: Tap water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: 23 ± 1 °C
- Ventilation: Well-ventilated room

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME ADMINISTERED: 6 mL/kg bw

Doses:

3.5, 4.2, 5.0 and 6.0 mL/kg bw

No. of animals per sex per dose:

Five

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: Yes

Statistics:

LD50 value was calculated according to the method of Weil (1952).

Results and discussion

Preliminary study:

Not applicable

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

4.2 mL/kg bw

Based on:

test mat.

95% CL:

3.27 - 5.37

Remarks on result:

other: equivalent to 4229 (3293-5408) mg/kg bw; calculated using the density of 1.007 g/L (literature)

Mortality:

Number of dead animals:
- At 3.5 mL/kg bw: 1/5 male and 2/5 females
- At 4.2 mL/kg bw: 2/5 males and 3/5 females
- At 5.0 mL/kg bw: 3/5 males and 4/5 females
- At 6.0 mL/kg bw: 3/5 males and 4/5 females

- Deaths occurred between 5 hours and 3 days after dosing.

Clinical signs:

other: - Sluggishness, sedation and ataxia were observed within a few hours after treatment and later, coma was frequently observed. - All survivors recovered gradually and appeared healthy at the end of the observation period.

Gross pathology:

- Gross observations at necropsy were normal for all of the surviving animals.

Other findings:

None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The oral LD50 of Reaction mass of 3,6-dihydro-4-methyl-2-phenyl-2H-pyran and tetrahydro-4-methylene-2-phenyl-2H-pyran, is higher than 2000 mg/kg bw in rats therefore it is not classified according to the Directive 67/548/EEC and the CLP Regulation.

Executive summary:

In an acute oral toxicity study performed similarly to OECD Guideline 401, groups of rats (5/sex/group) were given a single oral dose of Reaction mass of 3,6-dihydro-4-methyl-2-phenyl-2H-pyran and tetrahydro-4-methylene-2-phenyl-2H-pyran at 3.5, 4.2, 5.0 and 6.0 mL/kg bw. Animals were then observed for mortality and clinical signs for 14 days and all survivors were macroscopically necropsied after sacrifice.

Mortalities were 30, 50, 70 and 70 % at 3.5, 4.2, 5.0 and 6.0 mL/kg bw, respectively. Deaths occurred between 5 hours and 3 days after dosing. Sluggishness, sedation and ataxia were observed within a few hours after treatment and later, coma was frequently observed. All survivors recovered gradually, appeared healthy at the end of the observation period and presented a normal appearance at autopsy. In this study, the combined oral LD50 of Reaction mass of 3,6-dihydro-4-methyl-2-phenyl-2H-pyran and tetrahydro-4-methylene-2-phenyl-2H-pyran in rats was calculated to be 4.2 (3.27-5.37) mL/kg bw [equivalent to 4229 (3293-5408) mg/kg bw; calculated using the density of 1.007 g/L (literature)].

The oral LD50 of Reaction mass of 3,6-dihydro-4-methyl-2-phenyl-2H-pyran and tetrahydro-4-methylene-2-phenyl-2H-pyran is higher than 2000 mg/kg bw in rats therefore it is not classified according to the Directive 67/548/EEC and the CLP Regulation.