Registration Dossier

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

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: 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 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 levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
3 100 mg/kg bw
Based on:
test mat.
95% CL:
2 015 - 4 185
Sex:
female
Dose descriptor:
LD50
Effect level:
4 300 mg/kg bw
Based on:
test mat.
95% CL:
2 998 - 5 602
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.