Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 23 Feb, 1990 to April 2, 1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report Date:
1990

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EPA OPP 81-1 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
Relative humidity was outside the range specified in the guideline but it did not impact the results outcome.
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): MON 13900
- Physical state: Brown particles (powder)
- Lot/batch No.: DAY-8912-1370T
- Expiration date of the lot/batch: December, 1993 (est)
- Storage condition of test material: Room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Male and female young adult Sprague Dawley rats used in this study were obtained from Charles River Laboratories, Inc. (Portage, Michiganand Raleigh, North Carolina). The animals were individually housed in suspended stainless steel cages in an environment-controlled room with a 12-h light/dark cycle. Agway Prolab rodent feed and water were provided to each animal ad libitum. The rats were individually identified using metal ear tags and cage cards. All animals were allowed to acclimate to the laboratory environment for a minimum of 5 d prior to dosing.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
The test substance was ground and passed through a 40 mesh sieve prior to mixing with Mazola Corn Oil at a 25% w/v concentration. The dose volume administered was varied to achieve the designated mg/kg treatment levels.
Doses:
100, 500, 1000 and 1500 mg/kg bw
No. of animals per sex per dose:
5/dose (males) for 100 and 1500 mg/kg/ bw and 5/sex/dose for 500 and 1000 mg/kg/ bw
Control animals:
no
Details on study design:
All animals were fasted overnight prior to dose administration. The animals were observed frequently on the day of dosing and once daily thereafter for the duration of the study (Day 15). Mortality checks were performed twice daily. Individual body weights were determined and recorded on Days -1, 1, 8 and 15, or at death. All animals were subjected to a gross necropsy examination at the time of sacrifice (CO2, asphyxiation) or death.
Statistics:
LD50 values and 95% confidence intervals were calculated using the method of Litchfield and Wilcoxon.

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
1 250 mg/kg bw
Based on:
test mat.
95% CL:
>= 1.13 - <= 1.21
Remarks on result:
other: Slope was 1.17
Sex:
male
Dose descriptor:
LD50
Effect level:
521 mg/kg bw
Based on:
test mat.
95% CL:
>= 1.02 - <= 2.4
Remarks on result:
other: Slope was 1.57
Sex:
male/female
Dose descriptor:
LD50
Effect level:
869 mg/kg bw
Based on:
test mat.
95% CL:
>= 1.51 - <= 3.1
Remarks on result:
other: Slope was 2.17
Mortality:
All deaths in the LD50 animals occurred by study Day 5.
Clinical signs:
A variety of adverse clinical signs was observed in the LD50 study animals. The majority of the clinical signs occurred during study Days 1-5. The most notable clinical signs included decreased fecal output, reddish colored urine and urine stains. Additional indications of toxicity included decreased activity, tremors, breathing abnormalities, piloerection and apparent hypothermia.
Body weight:
Body weight gains were noted in all surviving animals during the test period.
Gross pathology:
No remarkable gross internal findings were noted in animals which survived. In animals which died, the most notable findings consisted of colored mucoid/fluid contents in the digestive tract, reddened stomach mucosa, black/red foci on the stomach and dark red foci on thymus.

Any other information on results incl. tables

Results:

Sex

Calculated LD50 value (mg/kg)

95% confidence interval (mg/kg)

Slope

95% confidence interval

Males

521

428-634

1.17

1.13-1.21

Females

1250

840-1858

1.57

1.02-2.43

Combined

869

566-1333

2.17

1.51-3.12

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Under the test conditions, the acute oral LD50 of MON 13900 for male and females rats was calculated to be 521 and 1,250 mg/kg bw respectively. The combined LD50 for both the sexes was calculated to be 869 mg/kg bw.
Executive summary:

A study was performed to assess theacute oral toxicityof MON 13900 in SD rat according to the EPA OPP 81-1 Guideline in compliance with GLP. Group of rats (5/dose for lowest and the highest dose and 5/sex/dose for the middle doses) were administered the test substance at 100, 500, 1,000 and 1,500 mg/kg bw.

A variety of adverse clinical signs were noted, including decreased fecal output, reddish coloured urine, urine stains, decreased activity, tremors, breathing abnormalities, piloerection and apparent hypothermia. The majority of these signs occurred during Days 1-5. All surviving animals exhibited body weight gains during the test period. The most notable necropsy observations occurred in the animals which died and consisted of abnormalities of the digestive tract and thymus.

Under the test conditions, the acute oral LD50 of the test substance for male and females rats was calculated to be 521 and 1,250 mg/kg bw respectively. The combined LD50 for both the sexes was calculated to be 869 mg/kg bw.