3,3'-methylenebis[5-methyloxazolidine]

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

October 30, 2001 to November 12, 2001 (experimental period)

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

According to the guideline the 2nd dose level should be 300 mg/kg bw (authors used 200 mg/kg bw; minor restriction).

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Principles of method if other than guideline:

The study was originally intended as Limit test (2000 mg/kg bw). As mortalities occured, the lower dose of 200 mg/kg bw was selected to establish the required information for hazard assessment and hazard classification according to Directive 67/548 EEC.

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3,3'-methylenebis[5-methyloxazolidine]

EC Number:

266-235-8

EC Name:

3,3'-methylenebis[5-methyloxazolidine]

Cas Number:

66204-44-2

Molecular formula:

C9H18N2O2

IUPAC Name:

3,3'-methylenebis[5-methyloxazolidine]

Details on test material:

- Name of test material (as cited in study report): 3,3'-Methylene-Bis(5-Methyl-Oxazolidine)
- Synonyms: Contram MBO (1/6120) Bakzid
- Substance type: Reaction product from paraformaldehyde and 2 hydroxypropylamine (ratio of 3:2
- Physical state: Clear colourless liquid
- Analytical purity: Content of formaldehyde 42,28%
- Purity test date: September 2001
- Lot/batch No.: 24773
- Expiration date of the lot/batch: No data
- Storage conditions: At room temperature in tightly closed original containers

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH, D 97633 Sulzfeld
- Age at study initiation: males 36 days, females 48 days
- Weight at study initiation: males 183-197 g and females 173-187 g at dosing
- Fasting period before study: 16 hours
- Housing: In groups of 3 in Macrolon Type 3 cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +-3°C
- Humidity (%): 55 +-15%
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From Sept 24, 2001 to Nov 12, 2001

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: Low dose: 10.7%; high dose undiluted
- Amount of vehicle (if gavage): 1.87 mL/kg bw
- Justification for choice of vehicle: To form a homogenous suspension
- Lot/batch no. (if required): 89 H 0149 (Sigma Aldrich)


MAXIMUM DOSE VOLUME APPLIED: 1.87 mL/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Study was intended tp be performed at Limit test at 2000 mg/kg bw. As mortalities occured, a lower does of 200 mg/kg bw was employed

Doses:

Single oral dose of 2000 and 200 mg/kg bw

No. of animals per sex per dose:

3 males and 3 females per dose group

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations 5, 15, 30, 60 min, and 3, 6, 24 h after application and then at least once daily.
Body weight measured day 0, 7, and 14.

- Necropsy of survivors performed: yes
- Necropsy of animals which died during post exposure

Statistics:

Calculation by means of regression analysis (Probit)

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 630 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No CL determined

Mortality:

2000 mg/kg bw: lethal for all rats within 6 h after application (except one male which died within 24 h)

200 mg/kg bw: no mortality.

Clinical signs:

other: Reduced motility, ataxia, reduced muscle tone and dyspnoea prior to death

Gross pathology:

No treatment related effects.

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral toxicity (LD50) was calculated to be at 630 mg/kg bw. for male and female rats

Executive summary:

Acute toxic class method according to OECD 423. Three males and 3 females per dose received 2000 or 200 mg/kg bw (10.7% in vehicle; high dose undiluted; volume of 1.87 ml/kg bw). All animals died at 2000 mg/kg bw. No mortality occured at 200 mg/kg bw. Afer 2 weeks of the post-exposure observation period, a necropsy was performed.

The acute oral toxicity was at 630 mg/kg bw. Classification: Harmful according to EC Commission Directive 67/548/EEC and subsequent Amendments.