[No public or meaningful name is available]

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From July 18, 2008 to August 20, 2008

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N-methyl-1-(trans-4-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)cyclohexyl)methanesulfonamide

Cas Number:

1208319-26-9

Molecular formula:

C15H23N5O2S

IUPAC Name:

N-methyl-1-(trans-4-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)cyclohexyl)methanesulfonamide

Specific details on test material used for the study:

Test material name in the study: PF-03394197-11
Lot Number: PF-01/115802/138A

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Rationale for alternative/additional species to rat (if applicable)
- Source: Charles River, Portage, Michigan
- Females (if applicable) nulliparous and non-pregnant: [yes/no]
- Rationale for use of males (if applicable)
- Age at study initiation: Approximately 7 weeks
- Weight at study initiation: Male: 220 to 225 g Female: 167 to 176 g
- Fasting period before study:
- Housing: Individual, stainless steel suspended wire mesh-type cages
- Historical data:
- Diet (e.g. ad libitum): Block Lab Diet® Certified Rodent Diet #5002, PMI Nutrition International, Inc. Ad libitum.
- Water (e.g. ad libitum): Automatic watering system, Ad libitum.
- Acclimation period: 7 days
- Microbiological status when known
- Method of randomisation in assigning animals to test and control groups

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 (±3) °C
- Humidity (%): 30 to 70%
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): Fluorescent lighting was provided for approximately 12 hours per day. The dark cycle was interrupted intermittently due to study-related activities.

Administration / exposure

Type of coverage:

occlusive

Vehicle:

other: Mineral oil

Details on dermal exposure:

TEST SITE
- Area of exposure: back of each animal
- % coverage: no less than 10% of the body surface area
- Type of wrap if used: the area was wrapped with gauze and secured with a non-irritating tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the wrappings were removed and the residual test article was removed using tepid tap water.
- Time after start of exposure: 24 hours

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The test animals were observed for clinical signs approximately 0.5, 2, and 4 hours after dosing on Day 1. Thereafter, the animals were observed for clinical signs once daily for 14 days. Observations included, but were not limited to, evaluation of the skin, fur, eyes, ears, nose, oral cavity, thorax, abdomen, external genitalia, limbs and feet, respiratory and circulatory effects, autonomic effects such as salivation, nervous system effects including tremors, convulsions, reactivity to handling, and bizarre behavior. Individual body weights were obtained on the day of arrival, just prior to test article administration (Day 1) and
weekly thereafter.
- Necropsy of survivors performed: Complete necropsy examinations were performed under procedures approved by a veterinary pathologist on all animals euthanized at scheduled necropsies. Euthanasia was by carbon dioxide inhalation followed by exsanguination from the abdominal vena cava. The animals were examined carefully for external abnormalities including palpable masses. The skin was reflected from a ventral midline incision, and any subcutaneous masses were identified and correlated with antemortem findings. The abdominal, thoracic, and cranial cavities were examined for abnormalities, and the organs were removed, examined, and the tissues and carcasses were discarded.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals survived to the scheduled necropsy on Day 15.

Clinical signs:

There were no treatment-related clinical findings. There were clinical findings that may have
been due to the wrapping and the use of Elizabethan collars that included red or brown
material around the eyes and nose and brown skin discoloration of the thoracic region and
sparseness of hair in the abdominal region which were observed very occasionally.

Body weight:

There were no treatment-related changes in body weight gains. The body weight gain of one
female animal (number 3006) was slightly lower than expected; however the body weight
gains of the remaining animals over the two week study period were considered normal.

Gross pathology:

No test article-related macroscopic observations were made in male or female rats.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal LD50 of the test item was greater than 2000 mg/kg in male and female rats.

Executive summary:

The acute dermal study is performed according to OECD Guideline 402 under GLP. The dermal LD50 of the test item was greater than 2000 mg/kg in male and female rats.