1-[(4-chlorophenyl)methyl]-1-cyclopentyl-3-phenylurea

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1988-08-02 to 1988-12-19

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EPA OPP 81-2 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1100 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 3

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

The most important deviations from the guideline was that an occlusive dressing instead of a porous gauze dressing was used. As the use of an occlusive dressing would increase effects, this deviation does not influence the conclusions of the study.

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1-[(4-chlorophenyl)methyl]-1-cyclopentyl-3-phenylurea

EC Number:

266-096-3

EC Name:

1-[(4-chlorophenyl)methyl]-1-cyclopentyl-3-phenylurea

Cas Number:

66063-05-6

Molecular formula:

C19H21ClN2O

IUPAC Name:

1-[(4-chlorophenyl)methyl]-1-cyclopentyl-3-phenylurea

Specific details on test material used for the study:

Physical Appearance: White powder

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 19 weeks.
- Weight at study initiation: 2.99 to 3.79 kg.
- Housing: individually in stainless steel cages with flat rod floors suspended over pelletized wood bedding or Alfa-cobs.
- Diet: ad libitum.
- Water: municipal, ad libitum.
- Acclimation period: at least six days.
- Method of randomisation in assigning animals to test and control groups: Rabbits were assigned to cages using a list of computer-generated random numbers. Animals were assigned to dose groups from consecutively numbered cages

ENVIRONMENTAL CONDITIONS
- Temperature: 18 to 24°C
- Humidity: 40 to 70%
- Photoperiod: 12-hour light/dark cycle.

Administration / exposure

Type of coverage:

occlusive

Vehicle:

water

Remarks:

The test material was moistened with municipal tap water

Details on dermal exposure:

TEST SITE
- Area of exposure: The back of each rabbit.
- coverage: 240 cm2 shaved area of the back.
- Type of wrap if used: The exposed area was covered with a square of gauze secured with hypoallergenic tape. The gauze was covered with a square of plastic secured with tape and adhesive bandage. A plastic collar was placed on the rabbits to prevent removal of the test material.

REMOVAL OF TEST SUBSTANCE
- The collar, tape, plastic and gauze were removed approximately 24 hours after treatment and the back was wiped using a paper towel dampened with tap water to remove all visible residue.
- Time after start of exposure: 24 hours.

TEST MATERIAL
- The test material was moistened with municipal tap water.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5/sex/group

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days.

- Frequency of observations and weighing: Clinical observations: twice daily on weekdays and once daily on weekends. Animals were weighed on the day of treatment and on days 7 and 14 after treatment. Terminal body weights were obtained on all animals. The body weight range on the day animals were treated was 2.99 to 3.42 kg for males and 3.27 to 3.79 kg for females.

- Necropsy of survivors performed: All animals were subjected to a gross pathologic examination. All rabbits which died during the study were necropsied as soon as possible. Survivors were sacrificed on day 14 after treatment.

- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other:

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No treatment-related deaths occurred at the dermal limit dose (2000 mg/kg bw), therefore, LD50 estimates were not determined. One male was found dead on day 2. This animal appeared to have died from a terminal Pasteurella multocida infection, as indicated by the lesions observed at necropsy. Further evidence that this animal did not die from the treatment include the absence of toxic signs in all animals and the absence of deaths and toxic signs in rats and mice administered this dose by the dermal route.

Clinical signs:

other: Lacrimation

Body weight:

other body weight observations

Remarks:

Body weight increased an average 0.11 kg from days 0-7 and from days 7-14

Gross pathology:

Lesions observed at gross necropsy were limited to lesions in the animal that was found dead on day 2.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal LD50 of pencycuron was found to be greater than 2000 mg/kg bw for rabbits, irrespective of sex. Pencycuron does not require classification for acute inhalation toxicity in any CLP category on the basis of this study.

Executive summary:

The acute dermal toxicity of pencycuron was tested using the dermal limit dose (2000 mg/kg bw) in young adult male and female New Zealand White rabbits (5/sex). There was no treatment-related mortality or clinical signs. Bodyweights were unaffected by treatment. The dermal LD₅₀ was >2000 mg/kg bw for males and females. Pencycuron does not require classification for acute inhalation toxicity in any CLP category on the basis of this study.