Tetramethylene dimethacrylate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Study performed before implementation of GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1978

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: Appraisal of the safety of chemicals in foods, drugs and cosmetics, by the Staft of the Division of Pharmacology, US FDA (1959)

Principles of method if other than guideline:

Study performed before implementation of the corresponding guideline, but performance complies to a large extent to the later implemented international guideline.

GLP compliance:

no

Remarks:

Study performed before implementation of GLP

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Tetramethylene dimethacrylate

EC Number:

218-218-1

EC Name:

Tetramethylene dimethacrylate

Cas Number:

2082-81-7

Molecular formula:

C12H18O4

IUPAC Name:

butane-1,4-diyl bis(2-methylacrylate)

Test material form:

liquid

Specific details on test material used for the study:

- Name of test material (as cited in study report): 1,4-Butandioldimethacrylat

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: no data
- Weight at study initiation: 160 – 240 g
- Fasting period before study: 16 h before study initiation
- Housing:individually
- Diet (e.g. ad libitum): laboratory rodents standard diet, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C
- Humidity (%): 45 – 55%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: no data

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 12.60 mL/kg bw

Doses:

7.94, 8.97, 10.00, 11.30, 12.60 mL/kg bw corresponding to 8131, 9185, 10240, 11571 and 12902 mg/kg bw

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: weighing day 0, day 14; clinical signs 20 min, 1 h, 3 h, 24 h, 7 d 14 d post application
- Necropsy of survivors performed: yes

Statistics:

LD50-calculation by probit analysis

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

10.066 mg/kg bw

Based on:

test mat.

95% CL:

9 400 - 10 035

Effect levels 2

Sex:

male/female

Dose descriptor:

LD50

Effect level:

9.83 mL/kg bw

Based on:

test mat.

95% CL:

9.18 - 10.47

Mortality:

- 7.94 mL/kg bw dose group: 1/5 males, 2/5 females died
- 8.97 mL/kg bw dose group: 2/5 males, 2/5 females died
- 10.00 mL/kg bw dose group: 3/5 males, 2/5 females died
- 11.30 mL/kg bw dose group: 3/5 males, 3/5 females died
- 12.60 mL/kg bw dose group: 4/5 males, 4/5 females died
animals died within 3 days p.a.

Clinical signs:

other: - reduced activity, piloerection and ataxia starting 1 to 3 hours after application, lasting for 24 hours; in the highest dose group lasting for 7 days

Gross pathology:

- redness of stomach and intestinal mucosa in died and surviving animals

Other findings:

n/a

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

On the basis of the results obtained after a single oral administration, the oral LD50 was determined to be 9.83 mL/kg bw corresponding to 10.06 g/kg bw referring to 100 % active substance (based on a density of 1.024 g/cm³).

Executive summary:

In an acute oral toxicity study similar to OECD guideline 401, groups of fasted Wistar rats (5 males + 5 females) were given a single oral dose of undiluted 1,4-BDDMA (according to supplier's information: purity ca. 90%, reactive ester content of 98 %) at doses of 7.94, 8.97, 10.00, 11.30 and 12.60 mL/kg (corresponding to 8131, 9185, 10240, 11571 and 12902 mg/kg bw based on a density of 1.024 g/cm³) and observed for 14 days.

  

The following mortality was observed: 1 male and 2 females in the 7.94 mL/kg dose group, 2 males and 2 females at 8.97 mL/kg, 3 males and 2 females at 10.00 mL/kg, 3 males and 3 females at 11.30 mL/kg, 4 males and 4 females at 12.60 mL/kg. The surviving animals showed reduced activity, piloerection and ataxia starting 1 to 3 hours after application and lasting for 24 hours; in the highest dose group the symptoms lasted up to 7 days. No changes in body weight gain were observed in the surviving animals throughout all dose groups. At necropsy redness of stomach and intestinal mucosa in died and surviving animals was observed.

Oral LD50 Combined = 9.83 mL/kg bw (95% c.i. 9.18 - 10.47 mL/kg bw) corresponding to 10.06 g/kg bw

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