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Toxicological information

Acute Toxicity: oral

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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 implementa tion of GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
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

Constituent 1
Chemical structure
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)
Details on test material:
- 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 levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
10.066 mg/kg bw
Based on:
test mat.
95% CL:
9 400 - 10 035
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:
- 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
Body weight:
- body weight gain of surviving animals was similar in all dose groups
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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