3,3'-methylenebis[5-methyloxazolidine]

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

September 24, 2001 to March 07, 2002 (date of Study Plan to Final Report date)

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

No data on the purity of the test substance

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 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

66204-44-02

IUPAC Name:

66204-44-02

Details on test material:

- Name of test material (as cited in study report): CONTRAM™MBO (1/6120) / Bakzid
- Substance type: Formaldehyde releaser
- Physical state: Clear colourless liquid
- Analytical purity: Content of formaldehyde 42,28%
- Composition of test material, percentage of components: 3,3'-methylenebis[5-methyl- oxazolidine]; releasable formaldehyde 43,52%; Reaction product from paraformaldehyde and 2 hydroxypropylamine (ratio of 3:2)
- Purity test date: Sept 10, 2001
- Lot/batch No.: 24773
- Expiration date of the lot/batch: No data
- Storage condition of test material: At room temperature in tightly closed container

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 33-43 d, females 44-56 d
- Weight at study initiation: Males 215-267 g and females 198-230 g at dosing
- Fasting period before study: 16 hours
- Housing: Single housing in Macrolon type III cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

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

IN-LIFE DATES: From November 8, 2001 to December 10, 2001 (day of dosing to termination of in-life phase)

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

corn oil

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal
- % coverage: 10
- Type of wrap if used: Gauze secured with adhesive plaster on the application site

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residues of test item (if any) were removed
- Time after start of exposure: 24 hours after administration

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.88 mL/kg bw
- Concentration (if solution): 13.3%, 40% in corn oil and undiluted
- Constant volume or concentration used: yes

Duration of exposure:

24 hours

Doses:

250, 750, and 2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations 5, 15, 30, 60 min, and 3, 6, 24 h after application and then at least once daily; weighing once weekly
- Necropsy of survivors performed: yes
- Other examinations: skin was observed for erythema and oedema and rated

Statistics:

LD50 calculated by means of regression analysis. The mortality rates at 24 hours and 14 days were used.

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 790 mg/kg bw

Based on:

test mat.

Remarks on result:

other: LD50 after 14 days. No CL determined.

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

>= 1 200 mg/kg bw

Based on:

test mat.

Remarks on result:

other: LD50 after 14 days. No CL determined

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

>= 760 mg/kg bw

Based on:

test mat.

Remarks on result:

other: LD50 after 14 days. No CL determined

Mortality:

see Table for Acute Dermal Toxicity

Clinical signs:

other: 250 mg/kg bw: no local or systemic effects 750 mg/kg bw: no local effects but reduced motility, ataxia, dyspnoea in all animals, 1/5 males with slightly reduced muscle tone. 2000 mg/kg bw, systemic effects: like mid dose group with some augmentation; sl

Gross pathology:

No treatment-related findings at necropsy except local effects in the high dose group: severe necrosis in 2/5 females

Any other information on results incl. tables

Table for Acute Dermal Toxicity

Dose [mg/kg bw]	Number of dead / number of investigated	Time of death (range)	Observations
250	males 0/5, females 0/5		See under Clinical signs
750	males 0/5, females 1/5	day 1
2000	males 5/5, females 5/5	day 1-7

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 in Sprague-Dawley rats was calculated to be 1200 mg/kg bw for males and 760 mg/kg bw for females.
The dose dependency of observed effects was demonstrated. The test substance showed local and systemic effects. The test substance hydrolysis in contact with water to formaldehyde and 2-hydroxypropylamine. Effects may be mostly related to the hydrolysis product formaldehyde.

Executive summary:

Study according to OECD guideline 402. Five males and 5 females per dose were exposed to 250, 750, and 2000 mg/kg bw (13.3 and 40% in corn oil and undiluted, volume 1.88 mL/kg bw; semi-occlusive). Termination 14 days after dermal exposure.

LD50 after 14 days: 1200 mg/kg bw for males and 760 mg/kg bw for females. Classification: harmful