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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:
1984-03-20 to 1984-04-11
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1984
Report date:
1984

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
adopted May 12, 1981
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Benzyl methacrylate
EC Number:
219-674-4
EC Name:
Benzyl methacrylate
Cas Number:
2495-37-6
Molecular formula:
C11H12O2
IUPAC Name:
benzyl 2-methylprop-2-enoate
Test material form:
liquid
Specific details on test material used for the study:
- Name of test material (as cited in study report): Methacrylate de Benzyle (MABz)

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 4 – 6 weeks
- Weight at study initiation: 101 – 196 g (males), 100 – 169 g (females)
- Fasting period before study: over night before study initiation, up to 2 h after administration
- Housing: in groups of 5 animals in polypropylene cages with sawdust bedding
- Diet (e.g. ad libitum): standard laboratory rodent diet ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 4°C
- Humidity (%): 45 – 60%
- Air changes (per hr): ca. 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE
no vehicle used

MAXIMUM DOSE VOLUME APPLIED:
7.77 mL/kg bw
Doses:
range finding study: 5000, 8000 mg/kg bw
main study: 4000, 5040, 6350, 8000 mg/kg bw
No. of animals per sex per dose:
range finding study: 2
main study: 5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 5 days (range finding study), 14 days (main study)
- Frequency of observations and weighing: Animals were observed 0.5, 1, 2, 3, 4 and 5 hours following dosing and then at least once daily for 14 days. Mortalities and evidence of overt toxicity were recorded at each observation. In addition individual bodyweights were recorded on days 0, 7 and 14.
- Necropsy of survivors performed: Surviving animals were killed on day 14. All animals that died during the study and those killed on day 14 were subjected to a macroscopic post mortem examination.
- Other examinations performed: -
Statistics:
LD50 and 95% confidence intervals were calculated according to Litchfield JT and Wilcoxon F (1949) J. Pharmac, Exp.Ther.96,99

Results and discussion

Preliminary study:
1/4 animals dead at 5000 mg/kg bw
4/4 animals dead at 8000 mg/kg bw
Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
3 980 mg/kg bw
Based on:
test mat.
95% CL:
2 760 - 5 730
Sex:
male
Dose descriptor:
LD50
Effect level:
4 820 mg/kg bw
Based on:
test mat.
95% CL:
3 950 - 5 880
Sex:
male/female
Dose descriptor:
LD50
Effect level:
4 450 mg/kg bw
Based on:
test mat.
95% CL:
3 620 - 5 470
Mortality:
- 4000 mg/kg bw: 1/5 males, 3/5 females dead
- 5040 mg/kg bw: 3/5 males, 4/5 females dead
- 6350 mg/kg bw: 4/5 males, 4/5 females dead
- 8000 mg/kg bw: 5/5 males, 5/5 females dead
Clinical signs:
- pilo-erection, hunched posture, decreased respiratory rate and lethargy was observed on all treatment groups shortly after dosing
- ptosis was observed in all animals of the 8000 mg/kg dose group
- ataxia, pallor of the extremi ties, body tremors, convulsions, loss of the righting reflex, increased lacrimation, abdominal discomfort and hind limb paralysis mainly prior to death in some rats.
- survivors had recovered on day 9
Body weight:
- reduced body weight gains in females at all dose levels in the first week; normal body weight gains in second week
- reduced body weight gains in males from 5040 mg/kg bw and higher; normal body weight gains in second week
Gross pathology:
- gross pathology of surviving animals revealed no abnormalities
- necropsy of the dead animals revealed haemorrhage of the lungs, pallor of the liver, spleen and kidneys and haemorrhage or inflammation of the glandular region of the stomach and/or small intestine

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)
Conclusions:
The acute oral LD50 of BNMA in rat is 4820 mg/kg bw (95% C.I. 3950 – 5880) in males and 3980 mg/kg bw (95% C.I. 2760 – 5730) in females. The combined oral LD50 is 4450 mg/kg bw (95% C.I. 6320 – 5470).
Executive summary:

In an acute oral toxicity study according to OECD guideline 401 (adopted May 12, 1981), groups of fasted, 4 to 6 weeks old, Sprague Dawley rats (5/sex) were given a single oral dose of BNMA at doses of 4000, 5040, 6350 and 8000 mg/kg bw and observed for 14 days.

Decreased respiratory rate, pilo-erection and lethargy was observed in all treatment groups shortly after dosing. Ptosis was observed in all animals of the 8000 mg/kg dose group. Ataxia, pallor of the extremities, body tremors, convulsions, loss of the righting reflex, increased lacrimation, abdominal discomfort and hind limb paralysis were mainly seen prior to death in some rats. Surviving animals had recovered on day 9.

Depressed bodyweight gains were recorded for female rats at all dose levels and male rats at 5040 mg/kg bw and above during the first week of observation only. Normal bodyweight gains were seen in all rats during Week 2. Gross pathology of surviving animals revealed no abnormalities. Necropsy of the dead animals revealed haemorrhage of the lungs, pallor of the liver, spleen and kidneys and haemorrhage or inflammation of the glandular region of the stomach and/or small intestine.

 

Oral LD50 Males = 4820 mg/kg bw (95% C.I. 3950 – 5880)

      Females = 3980 mg/kg bw (95% C.I. 2760 – 5730)

      Combined = 4450 mg/kg bw (95% C.I. 6320 – 5470)

GHS criteria not met

 

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