Propylidynetrimethyl trimethacrylate

Acute Toxicity: other routes

Administrative data

Endpoint:

acute toxicity: other routes

Type of information:

experimental study

Adequacy of study:

key study

Study period:

October/November 1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1982

Report date:

1982

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The purpose of this study was to evaluate the acute toxicity of the test mateiral when administered by intraperitoneal injection to rats ; to determine the intraperitoneal LD50 of the material; and to determine whether neurologic effects could be produced with acute administration.

GLP compliance:

no

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Propylidynetrimethyl trimethacrylate

EC Number:

221-950-4

EC Name:

Propylidynetrimethyl trimethacrylate

Cas Number:

3290-92-4

Molecular formula:

C18H26O6

IUPAC Name:

2,2-bis[(methacryloyloxy)methyl]butyl methacrylate (non-preferred name)

Test material form:

liquid

Details on test material:

- Physical state: amber liquid
- Storage condition of test material: at room temperature

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 Breeding Laboratories, Inc. Wilmington, Massachussets
- Age at study initiation: "young adults" no details
- Weight at study initiation: males = 252-302 g, Females = 214-268 g
- Fasting period before study: no data
- Housing: individually during the study, in suspended, stainless steel cages with wire mesh bottoms.
- Diet (e.g. ad libitum): Purina Laboratory Chow, ad libitum
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: 16-17 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 68-76°F
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

corn oil

Details on exposure:

The test and control material were administered by intraperitoneal injection using a syringe of appropriate size, fitted with a 21 gauze needle.
Concentration = 16.7 µ w/w in corn oil.

Doses:

4 doses: 2000-3500-5000-8000 mg/kg

No. of animals per sex per dose:

5 rats/sex/dose

Control animals:

no

Details on study design:

Duration of total observation = 14 days
Viability checks : twice daily.
Observation for pharmacologic and toxicologic signs : 1, 2, 4 and 24 hours after dosing, and daily thereafter for 14 days.
Neurologic examination: 1, 2, 4 and 24 hours after dosing, and up to Day 14.
Body weights: pretest, day of dosing, day 7 and 14, at terminal (for any animal which did not survive for 14 days).
No postmortem examination on survival animals.

Statistics:

no

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

3 100 mg/kg bw

Based on:

test mat.

95% CL:

2 015 - 4 185

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

4 300 mg/kg bw

Based on:

test mat.

95% CL:

2 998 - 5 602

Effect levels 3

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3 900 mg/kg bw

Based on:

test mat.

95% CL:

3 187 - 4 613

Mortality:

At 2000 mg/kg : 0/5 males, 0/5 females
At 3500 mg/kg : 4/5 males and 0/5 females; time of death = 5-7 days
At 5000 mg/kg : 4/5 males and 5/5 females; time of death = 2-9 days
At 8000 mg/kg : 5/5 males and 4/5 females; time of death = 2-5 days

Clinical signs:

Animals at all dose levels exhibited a number of neurologic abnormalities. Signs seen in animals which survived as well as those which included tremors, convulsions, ataxia, apparent hallucinations, head-searching behavior, alterations in limb and body tone (flaccidity or rigidity)., pelvic elevation, and impaired pupillary, righting, visual placing, toe pinch and startle reflexes. Signs seen only in animals which died (generally in single animals) included circling, pranding, spasticity, compulsive biting and impaired corneal reflex.

Soft stool and fecal staining occurred in both corn oil and test material-treated animals and was, not considered related to test material administration.
Signs seen in several test material-treated animals during the post-dose period included decreased activity, hyperpnea, food consumption decrease, unthrifty coat and a number of other abnormalities.

Body weight:

Animals which died exhibited substantial weight losses prior to death. Most survivors exhibited weight losses at day 7 with subsequent gains between days 7 and 14.

Gross pathology:

Animals which died and those which were killed after 14 days exhibited a large number of postmortem abnormalities, most notably in the abdominal viscera. Most of these appeared to represent irritation and/or infectious sequelae resulting from intraperitoneal injection of the vehicle and/or test material.

Other findings:

no

Applicant's summary and conclusion

Conclusions:

In this study, the ip LD50 for propylidynetrimethyl trimethacrylate is 3900 mg/kg bw in male and female rats.

Executive summary:

The purpose of this study was to evaluate the acute toxicity of the test mateiral when administered by intraperitoneal injection to rats ; to determine the intraperitoneal LD50 of the material; and to determine whether neurologic effects could be produced with acute administration.

Five male five female rats were given a single oral dose of propylidynetrimethyl trimethacrylate at the dose of 2000, 3500, 5000 and 8000 mg/kg bw.

No animal died at 2000 mg/kg, however 4 males died at 3500 mg/kg, 4 males and 5 females at 5000 mg/kg, and 5 males and 4 females at 8000 mg/kg. Animals at all dose levels exhibited a number of neurologic abnormalities. Signs seen in animals which survived as well as those which included tremors, convulsions, ataxia, apparent hallucinations, head-searching behavior, alterations in limb and body tone (flaccidity or rigidity)., pelvic elevation, and impaired pupillary, righting, visual placing, toe pinch and startle reflexes. Signs seen only in animals which died (generally in single animals) included circling, pranding, spasticity, compulsive biting and impaired corneal reflex. Soft stool and fecal staining occurred in both corn oil and test material-treated animals and was, not considered related to test material administration. Signs seen in several test material treated animals during the post-dose period included decreased activity, hyperpnea, food consumption decrease, unthrifty coat and a number of other abnormalities. Animals which died and those which were killed after 14 days exhibited a large number of postmortem abnormalities, most notably in the abdominal viscera. Most of these appeared to represent irritation and/or infectious sequelae resulting from intraperitoneal injection of the vehicle and/or test material.

To conclude, the ip LD50 for propylidynetrimethyl trimethacrylate is 3900 mg/kg bw in male and female rats.