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Administrative data

Endpoint:
acute toxicity: other routes
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1984
Report date:
1984

Materials and methods

Principles of method if other than guideline:
A single dose was administered i.p. to each aninmal followed by 14 days of observations. Range-finding animals were observed for 7 days.
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Glycerol, propoxylated, esters with acrylic acid
EC Number:
500-114-5
EC Name:
Glycerol, propoxylated, esters with acrylic acid
Cas Number:
52408-84-1
Molecular formula:
(C3H6O)m(C3H6O)n(C3H6O)oC12H14O6
IUPAC Name:
Poly[oxy(methyl-1,2-ethanediyl)], .alpha.,.alpha.',.alpha.''-1,2,3- propanetriyltris[.omega.-[(1-oxo-2-propenyl)oxy]]-
Test material form:
liquid
Details on test material:
Name in study report: C-663
Specific details on test material used for the study:
Lot/batch No.of test material: P.O. No. 040-014-31-4

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, Wilmington, Massachusetts
- Age at study initiation: 9 - 12 weeks
- Weight at study initiation: males: 273 - 338g, females: 227 - 256g
- Housing: groups of 6 animals during acclimatization, single during the study period in stainless steel cages with wire mesh bottoms
- Diet: ad lib.
- Water: ad lib.
- Acclimation period: 16 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 25
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
corn oil
Details on exposure:
After the initial range-finding study it was decided to dilute the material in corn oil to decrease the intraperitoneal irritation and to be consistent with previous intraperitoneal studies with similar materials. In this range finding study, one animal per sex and dose was exposed intraperitoneally to 50, 100, 500, 1000, 2000 mg/kg bw undiluted substance or to 10, 100, 1000 mg/kg test material diluted in corn oil. The concentration of the test material in corn oil was 0.1 g/mL.
Doses:
0, 25, 73, 214, 625 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: Viability: twice daily
- Necropsy of survivors performed: no
- Clinical signs: 1, 2, 4h after dosing, daily thereafter; body weight: pre-dosing, days 7 + 14
- Gross pathology examinations of all animals on day of death or after euthanisation

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
330 mg/kg bw
Based on:
test mat.
95% CL:
>= 223 - <= 437
Sex:
female
Dose descriptor:
LD50
Effect level:
250 mg/kg bw
Based on:
test mat.
95% CL:
>= 33 - <= 467
Sex:
male
Dose descriptor:
LD50
Effect level:
390 mg/kg bw
Based on:
test mat.
95% CL:
>= 149 - <= 631
Mortality:
25 mg/kg: 0/10
73 mg/kg: 0/10
214 mg/kg: 2/10 (2f)
625 mg/kg: 9/10 (4m, 5f)
Clinical signs:
- Antemortem in the 214 + 625 mg/kg groups: clonic convulsions, ataxia, flaccid limb and body tone, abnormal righting, visual placing, startle and toe pinch reflexes, persistent pupillary constriction with no light response.
- Occasional occurences of pupillary constriction with no light response were seen in survivors in the 25, 73, and 214 mg/kg groups. All surviving animals were free of signs by day 2
Body weight:
Comparable between survivors and controls
Gross pathology:
All animals which died, and some animals which were killed after 14 days exhibited several 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.

Applicant's summary and conclusion