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Toxicological information

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:
The study was performed between 12 August 1994 and 12 December 1994.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not effect the quality of the relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report date:
1994

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
EPA OTS 798.1175 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
no

Test material

Constituent 1
Details on test material:
Sponsor's identification: N-(n-butyl) thiophosphoric triamide (NBPT)
-Substance type: Organic
Physical state:: Light-tan, waxy solid
Analytical purity: 87 %
Batch number: Not reportded
Date received: Not reported
Storage conditions: The test material was stored refrigerated before the range-finding study, then was moved to room temperature storage.

Test animals

Species:
rat
Strain:
other: Cr1:CD®(SD)BR
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Inc., Portage, Michigan
- Age at study initiation: Young adult
- Weight at study initiation:
15 male and 15 female rats, weighing from 240 to 294 g

- Fasting period before study:
approximately 17 to 20 hours before test material administration
- Housing:
the animals were separated by sex and group housed in screen-bottom stainless steel cages in temperature- and humidity-controlled quarters. During the range-finding study, the animals were individually housed.
- Diet (e.g. ad libitum):
Laboratory Rodent Diet #5001, PMI Feeds, Inc.
- Water (e.g. ad libitum):
Ad libitum from an automatic system. Samples of the water are analyzed by HWI for total dissolved solids, hardness, and specified microbiological content and for selected elements, heavy metals, organophosphates, and chlorinated hydrocarbons
- Acclimation period:
At least 7 days
-Contaminants:
There were no known contaminants in the feed or water at levels that would have interfered with or affected the results of the study
ENVIRONMENTAL CONDITIONS
- Temperature (°C):
19 to 25°C
- Humidity (%):
50% ± 20%,
- Air changes (per hr):
Not stated
- Photoperiod (hrs dark / hrs light):
12-hour light/12-hour dark cycle.
IN-LIFE DATES:
In-life Start Date: 18 August 1994
In-life Termination Date: 4 October 1994

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: Not reported
- Amount of vehicle (if gavage): Not reported
- Justification for choice of vehicle: Not reported

MAXIMUM DOSE VOLUME APPLIED:
20 mL/kg of body weight

DOSAGE PREPARATION:
The test material was mixed with distilled water to a specific concentration for each dose level. Each prepared test mixture appeared to be a suspension. An individual dose of each respective test mixture was calculated for each animal based on its fasted body weight and administered by gavage to a volume of 20 mL/kg of body weight. The test mixtures were stored at room temperature until administered.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:
Not reported
Doses:
Range-Finding Study:
500, 1,000, 3,000, and 5,000 mg/kg bw

Definitive Study:
1,000, 2,500, and 5,000 mg/kg bw (Males)
1,000, 2,500, and 3,000 mg/kg bw (females)
No. of animals per sex per dose:
Range-finding Study:
eight healthy, acclimated rats (one/sex/dose level)

Definitive Study:
5 males and 5 females per dose level
Control animals:
no
Details on study design:
- Duration of observation period following administration:
14 days

- Frequency of observations and weighing:
The range-finding animals were observed for mortality only on the day of treatment and for 14 days thereafter. Clinical observations and mortality checks for the definitive study animals were conducted at approximately 1, 2.5, and 4 hours after test material administration. Additional clinical observations and twice a day mortality checks (morning and afternoon) were conducted daily thereafter for 14 days.

Body weights for range-finding and definitive study animals were determined before test material administration (Day 0). Additional body weights were determined at Day 7, at termination of the experimental phase (Day 14), or at death when survival exceeded 1 day.

- Necropsy of survivors performed:
Yes

- Other examinations performed:
Clinical signs.
Statistics:
The LD50 value for males, females, and the sexes combined was determined by a computer program using a modified Behrens-Reed-Muench cumulant method. No other statistical analyses were required by the protocol.

Results and discussion

Preliminary study:
Not applicable.
Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
3 536 mg/kg bw
Based on:
test mat.
95% CL:
2 147 - 5 824
Sex:
female
Dose descriptor:
LD50
Effect level:
2 603 mg/kg bw
Based on:
test mat.
95% CL:
1 885 - 3 595
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 823 mg/kg bw
Based on:
test mat.
95% CL:
2 823 - 3 652
Mortality:
All mortality occurred within 2 days of test material administration. Based on the observed mortality, the estimated oral LD50 in rats was determined to be 3,536, 2,603, and 2,823 mg/kg for males, females, and the sexes combined, respectively.
Clinical signs:
Clinical signs of toxicity included thin appearance, hunched posture, staggered gait, hypoactivity, absence of pain and/or righting reflex, hypothermic to touch, prostration, red or yellow-stained face, lacrimation, miosis, excessive salivation, dyspnea, bradypnea, soft stool, wet urogenital area, and dark- or yellow-stained urogenital area. All surviving animals returned to a normal appearance by Day 5 after treatment.
Body weight:
There was no meaningful effect on body weight gain in surviving animals
Gross pathology:
There were 10 rats (five males and five females) each from dose levels of 1,000 and 2,500 mg/kg, five females from a dose level of 3,000 mg/kg, and five
males from a dose level of 5,000 mg/kg necropsied. Some animals died on test (DOT) and the remaining surviving animals were euthanized and necropsied at
the termination of the study.

At necropsy, the most prominent finding in the DOTs pertained to coloration changes and the contents of the gastrointestinal tract. The stomach and small
intestines contained yellow oily semifluid which possibly represented test material mixed with ingesta. The urinary bladder in some animals were apparently distended with yellow or red fluid. The bladder wall or mucosa in two animals given 5,000 mg/kg was diffusely dark red or had multiple dark red areas of variable size. These changes were possibly caused by the test material but may also be related to post mortem autolysis. All remaining observations in these animals andthe animals surviving to study termination were considered incidental findings and unrelated to the test material.
Other findings:
- Organ weights:
Not recorded

- Histopathology:
Not recorded

- Potential target organs:
Not recorded

- Other observations:
Not recorded

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight.
Executive summary:

Introduction. 

The study was performed to assess the acute oral toxicity of the test material in the young adult albino rats of the Crl:CD®(SD)BR strain procured from Charles River Laboratories, Inc., Portage, Michigan. The method was designed to meet the EPA Guidelines: EPA OTS 798.1175 (Acute Oral Toxicity).

Method. 

The objective of this study was to assess the acute oral toxicity produced when the test material is administered by the oral route (gavage) to rats.

The test material, N-(n-butyl) thiophosphoric triamide (NBPT), was evaluated for its acute oral toxicity potential in male and female rats when administered as a single gavage dose at levels of 1,000, 2,500, and 5,000 mg/kg of body weight in males and at 1,000, 2,500, and 3,000 mg/kg in females. The estimated oral LD50 in rats was determined to be 3,536, 2,603, and 2,823 mg/kg for males, females, and the sexes combined, respectiv

Mortality. 

All mortality occurred within 2 days of test material administration.

Clinical Observations. 

Clinical signs of toxicity included thin appearance, hunched posture, staggered gait, hypoactivity, absence of pain and/or righting reflex, hypothermic to touch, prostration, red or yellow-stained face, lacrimation, miosis, excessive salivation, dyspnea, bradypnea, soft stool, wet urogenital area, and dark- or yellow-stained urogenital area. All surviving animals returned to a normal appearance by Day 5 after treatmen

Bodyweight. 

There was no meaningful effect on body weight gain in surviving animal

Necropsy. 

Test material-related findings observed at necropsy were limited to those animals dying during the study and pertained to coloration changes and the contents of the gastrointestinal tract

Conclusion. 

The acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight.