Nitrapyrin

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

15 November 1985 to 25 February 1986

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted to sound scientific principles with a sufficient level of detail to assess the quality of the submitted data.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

no

Remarks:

The report states that it was conducted with the intent of GLP

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Nitrapyrin

EC Number:

217-682-2

EC Name:

Nitrapyrin

Cas Number:

1929-82-4

Molecular formula:

C6H3Cl4N

IUPAC Name:

2-chloro-6-(trichloromethyl)pyridine

Test material form:

other: solid (unspecified)

Details on test material:

- Appearance: white solid

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2.5 - 2.8 kg
- Fasting period before study: no
- Housing: animals were housed individually
- Diet: 4 ounces of feed were provided daily
- Water: tap water, ad libitum
- Acclimation period: at least 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2 °C
- Humidity (%): 40 - 60 %
- Air changes (per hr): approximately 10 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours of darkness / 12 hours of light

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Approximately 24 hours prior to application of the test material, the dorsal and ventral areas of the rabbits were clipped free of hair.
- Type of wrap if used: The test material was applied to the back of each animal and held in contact with the skin with a porous gauze dressing and non-irritating tape. A heavy-gauge plastic cuff was next placed over the trunk of the animal and secured with rubber bands. Five mL of water were injected under the plastic cuff to enhance skin contact. The plastic cuff was then covered by a cloth bandage, which was taped securely to the adjacent hair.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Following a 24-hour exposure period, the cuffs were removed and observations were made for any reaction at the site of application. The skin was washed with mild soap and water, rinsed thoroughly and dried with a soft disposable towel. The rabbits were then fitted with a plastic collar to prevent them from ingesting any residue of the material which may have remained on them after washing. The collars were removed approximately 48 hours later.

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 animals per sex

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed closely on the day of treatment and then each working day for the next two weeks. Routine monitoring on weekends was limited to animal husbandry procedures required to ensure the availability of food and water. Observations included but were not limited to changes in respiration, demeanour, onset of lethargy, or unconsciousness. All clinical observations were recorded. The rabbits were weighed prior to treatment (Day 0), and at 1, 7 and 14 days post-treatment.
- Necropsy of survivors performed: yes.
All animals were submitted for a complete necropsy examination by a veterinary pathologist. Rabbits submitted at necropsy were anesthetised with CO2 and euthanatised. The eyes were examined in situ with a microscope slide and fluorescent illumination.

Statistics:

Means and standard deviations were calculated and used to describe animal body weight changes. No statistical outliers were identified (Grubbs, 1969).

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None of the animals died during the study.

Clinical signs:

other: Following treatment, lethargy and an apparent decrease in appetite were observed in all rabbits. Rapid shallow respiration was also observed in approximately half of the animals.

Gross pathology:

Gross pathologic observations for male and female rabbits revealed that all rabbits were within normal limits with the exception of one male (unilateral adhesions in the eyes) and one female (increased spleen size) which had observations that were considered nonspecific and not related to treatment.

Other findings:

Slight erythema was observed on the application sites of eight rabbits, two rabbits showed moderate erythema.

Applicant's summary and conclusion

Interpretation of results:

not classified

Conclusions:

Under the conditions of the study the acute dermal LD50 of the test material was determined to be in excess of 2000 mg/kg bw when administered to New Zealand White rabbits.

Executive summary:

The acute dermal toxicity of the test material was investigated in a study which was conducted following a method which was similar to that of the standardised guideline OECD 402.

During the study, a group of 5 male and 5 female New Zealand White rabbits were dermally treated with 2000 mg/kg test material moistened with water. Animals were exposed to test material in an occlusive fashion for a period of 24 hours.

All rabbits survived the two-week observation period. Following treatment, lethargy and an apparent decrease in appetite were observed in all rabbits, rapid shallow respiration was also observed in approximately half of the animals. Twenty-four hours post-treatment, slight to moderate erythema was observed on the skin at the site of application. A slight decrease in weight was observed in most rabbits following treatment. At the end of the two week study however, the majority of rabbits had gained weight. Gross necropsy revealed all rabbits within normal limits with the exception of one male and one female which had observations that were considered nonspecific and not related to treatment.

Under the conditions of the study the acute dermal LD50 of the test material was determined to be in excess of 2000 mg/kg bw when administered to New Zealand White rabbits.