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Toxicological information

Acute Toxicity: dermal

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Administrative data

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.

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 798.1100 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

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:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system 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

Administration / exposure

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.

Results and discussion

Preliminary study:
Not applicable
Effect levels
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.

Applicant's summary and conclusion

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