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Description of key information

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. The estimated dermal LD50 for male and female rabbits was determined to be greater than 2,000 mg/kg. 

 

The LC50 of NBPT was >2.2 mg/L when male and female Crl:CD(SD) albino rats were exposed to a dust aerosol as a single 4 hour nose-only exposure.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
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.
Qualifier:
according to
Guideline:
EPA OTS 798.1175 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
no
Species:
rat
Strain:
other: Cr1:CD®(SD)BR
Sex:
male/female
Details on test animals 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
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.
Preliminary study:
Not applicable.
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
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.

Endpoint conclusion
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Study initiation: 22 Jan 2015, experimental completion: 17 Feb 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
fixed concentration procedure
Limit test:
yes
Species:
rat
Strain:
other: Crl:CD(SD)
Sex:
male/female
Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
air
Mass median aerodynamic diameter (MMAD):
3.3 µm
Geometric standard deviation (GSD):
2.62
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
>= 4 h
Remarks on duration:
Exposure was paused and the system cleaned after approximately 1, 2 & 3 hours due to test material blocking the delivery apparatus. Cleaning time was 11 minutes, resulting in an exposure period of 4 h 11 min.
Concentrations:
2.2 mg/l
No. of animals per sex per dose:
5/sex/dose
Control animals:
no
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 2.2 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
None
Clinical signs:
other: Increased respiration for 1 male and 2 females, 1 - 2 hours post exposure. Vocalisation upon handling for 1 female. White material around the nose immediately following exposure was attributed to the test substance; red material around eyes and nose. Yel
Body weight:
Males lost 3-7 grams and 4 females lost 1-14 grams. All animals surpassed initial bodyweight by study day 14 and were considered normal.
Gross pathology:
1 male had misshapen spleen.

There were no other findings.
Interpretation of results:
GHS criteria not met
Conclusions:
The LC50 of NBPT was >2.2 mg/L when male and female Crl:CD(SD) albino rats were exposed to a dust aerosol as a single 4 hour nose-only exposure.
Executive summary:

The LC50 of NBPT was >2.2 mg/L when male and female Crl:CD(SD) albino rats were exposed to a dust aerosol as a single 4 hour nose-only exposure.

Endpoint conclusion
Dose descriptor:
LC50
Value:
2 200 mg/m³

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Between 12 August and 11 November 1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.
Qualifier:
according to
Guideline:
EPA OTS 798.1100 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
Test Animals:
Animals:
Hra:(NZW)SPF strain

Rationale: Historically, the New Zealand White albino rabbit has been the animal of choice because of the large amount of background information on this species.

- Source: from HRP, Inc., Kalamazoo, Michigan

- Age at study initiation:
Adult albino rabbits
- Weight at study initiation:
2,409 to 2,775 g
- Fasting period before study: Not stated
- Housing:
animals were individually housed in screen-bottom stainless steel cage
- Diet:
a measured amount of Laboratory Rabbit Diet HF #5326, PMI Feeds,
- Water:
water ad libitum
- Acclimation period:
at least 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C):
19° to 23°C
- Humidity (%):
relative humidity of 50% ±20%
- Air changes (per hr):
Not stated
- Photoperiod (hrs dark / hrs light):
12-hour light/12-hour dark lighting cycle

IN-LIFE DATES: From: To:
In-life Start Date: 17 August 1994
In-life Termination Date: 31 August 1994

Type of coverage:
occlusive
Vehicle:
other: Each dose was thoroughly moistened with distilled water before application
Details on dermal exposure:
TEST SITE
- Area of exposure:
- % coverage:
not less than 10% of the total body surface

- Type of wrap if used:
The area of application was covered with a 10-cm x 10-cm gauze patch secured with paper tape and overwrapped with Saran Wrap® and Elastoplast® tape to provide an occlusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done):
the test sites were washed using tap water and disposable paper towels.

- Time after start of exposure:
24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):
0.05 g/cm2

- Concentration (if solution): Not applicable
- Constant volume or concentration used: yes
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): Not applicable
- Concentration (if solution): Not applicable
- Lot/batch no. (if required): not applicable
Duration of exposure:
24 hours
Doses:
2000 mg /kg body weight
No. of animals per sex per dose:
5 per sex per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration:
14 days

- Frequency of observations and weighing:
Clinical observations and mortality checks 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 were determined before test material application (Day 0), at Day 7, and at termination of the experimental phase (Day 14).

The initial dermal irritation reading was made approximately 30 minutes after removal’of the test material according to the Draize technique (recorded as the Day 1 score). Subsequent readings of dermal irritation were made on Days 3, 7, 10, and 14.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
Statistics:
No statistical analysis was performed.
Preliminary study:
Not applicable
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 95% confidence limits not reported.
Mortality:
No mortality was observed during the study.


Clinical signs:
All animals appeared normal with the exception of 4 animals which exhibited soft stool on Days I and/or 2. All animals returned to a normal appearance by Day 3 after treatment.
Body weight:
All animals showed expected gains in bodyweight over the study period.
Gross pathology:
There were 10 rabbits (five males, and five females) euthanized and necropsied at the termination of the study. There were no visible lesions in any of the animals.
Other findings:
None.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material, N-(n-butyl) thiophosphoric triamide (NBPT), was evaluated for its acute dermal toxicity potential in male and female rabbits when administered as a single topical application at a level of 2,000 mg/kg of body weight. The estimated dermal LD50 for male and female rabbits was determined to be greater than 2,000 mg/kg

Executive summary:

The study was conducted in accordance with the EPA Guidelines, EPA OTS 798.1100 (Acute Dermal Toxicity)

The objective of this study was to assess the systemic toxicity and relative skin irritancy of a test material when applied to the skin of dult albino rabbits of the Hra:(NZW)SPF strain procured from HRP, Inc., Kalamazoo, Michigan. The test material, N-(n-butyl) thiophosphoric triamide (NBPT), was evaluated for its acute dermal toxicity potential in male and female rabbits when administered as a single topical application at a level of 2,000 mg/kg of body weight. The estimated dermal LD50 for male and female rabbits was determined to be greater than 2,000 mg/kg. All animals appeared normal with the exception of 4 animals which exhibited soft stool on Days 1 and/or 2. All animals returned to a normal appearance by Day 3 after treatment.

Mortality. There were no deaths.

Clinical Observations. There were no signs of systemic toxicity.

Dermal Irritation.  The test material produced slight to severe dermal irritation.

Bodyweight. All animals exhibited body weight gain throughout the stud

Necropsy.  The gross necropsy at termination revealed no visible lesions.

Conclusion.  The test material, N-(n-butyl) thiophosphoric triamide (NBPT), was evaluated for its acute dermal toxicity potential in male and female rabbits when administered as a single topical application at a level of 2,000 mg/kg of body weight. The estimated dermal LD50 for male and female rabbits was determined to be greater than 2,000 mg/kg

Endpoint conclusion
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Acute Oral Toxicity 

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).

 

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.

Acute Inhalation Toxicity

The LC50 of NBPT was >2.2 mg/L when male and female Crl:CD(SD) albino rats were exposed to a dust aerosol as a single 4 hour nose-only exposure.

There was no mortality.

Acute Dermal Toxicity

The study was conducted in accordance with the EPA Guidelines, EPA OTS 798.1100 (Acute Dermal Toxicity)

The objective of this study was to assess the systemic toxicity and relative skin irritancy of a test material when applied to the skin of dult albino rabbits of the Hra:(NZW)SPF strain procured from HRP, Inc., Kalamazoo, Michigan. The test material, N-(n-butyl) thiophosphoric triamide (NBPT), was evaluated for its acute dermal toxicity potential in male and female rabbits when administered as a single topical application at a level of 2,000 mg/kg of body weight. The estimated dermal LD50 for male and female rabbits was determined to be greater than 2,000 mg/kg. All animals appeared normal with the exception of 4 animals which exhibited soft stool on Days 1 and/or 2. All animals returned to a normal appearance by Day 3 after treatment.

The estimated dermal LD50 for male and female rabbits was determined to be greater than 2,000 mg/kg

Justification for classification or non-classification

The test material is considered non-classified with regards to Acute toxicity.