[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:

24th January 2012 to 10th April 212

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

This study was designed to comply with the standards set forth in 49 CFR 173.132(b)(2)

GLP compliance:

yes

Test type:

fixed dose procedure

Test material

Test material information

Constituent 1

Reference substance name:

{1-(ETHYLSULFONYL)-3-[4-(4,4,5,5-TETRAMETHYL-1,3,2-DIOXABOROLAN-2-YL)-1H-PYRAZOL-1-YL]AZETIDIN-3-YL}ACETONITRILE

Cas Number:

191987-50-5

Molecular formula:

C16H25BN4O4S

IUPAC Name:

{1-(ETHYLSULFONYL)-3-[4-(4,4,5,5-TETRAMETHYL-1,3,2-DIOXABOROLAN-2-YL)-1H-PYRAZOL-1-YL]AZETIDIN-3-YL}ACETONITRILE

Test material form:

solid: particulate/powder

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

Animals were received on 25 Jan 2012. Following an acclimation period of at least one week, three healthy male and three healthy, non- pregnant and nulliparous female New Zealand White rabbits were assigned to the treatment group without conscious bias.
The animals were born on 13 Aug 2011 & 20 Aug 2011. The pretest body weight range was 2.5 - 3.0 kg for males and 2.4 - 2.7 kg for females. The animals were identified by cage notation and a uniquely numbered metal eartag and individually housed in suspended stainless wire bottom cages. Absorbent paper bedding was placed beneath the cages and changed at least three times per week. Fresh PMI Rabbit Chow (Diet #5321) was provided daily. Water was available ad libitum. The animal room, reserved exclusively for rabbits on acute tests, was temperature controlled, had a 12 hour light/dark cycle, and was kept clean and vermin free.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Details on dermal exposure:

Site Preparation
Prior to application of the test article, the dorsal trunk of the animal was clipped. The area began at the shoulders and extended to the hip bone and half way down the flank of each side of the animal.
Dosing
A single dose of the test article was moistened with 3.0 ml of distilled water to form a paste and applied to the prepared site under a 10 x 15 cm porous gauze patch at a dose level of 1000 mg/kg. The dose was based on the dry weight of the test article. Gentle pressure was applied to the gauze to aid in the distribution of the test substance over the prepared site. The torso was covered with a piece of porous dressing (semi-occlusive) large enough to cover the dose site with at least 5 cm square to spare on all sides of the gauze patch. Porous, non-irritating tape was used to encircle the trunk of the animal. The test article remained in contact with the skin for 24 hours at which time the wrappings were removed. Residual test article was removed by gently washing with distilled water.

Duration of exposure:

24 hours

Doses:

One - 1000mg/kg

No. of animals per sex per dose:

3

Control animals:

not required

Details on study design:

Type and Frequency of Observations
In vivo - The test sites were scored for dermal irritation at 24 hours post-dose and on Days 7 and 14 using the numerical Draize scoring code.

The animals were observed 1 and 2 hours post-dose and once daily for 14 days for mortality, toxicity and pharmacological effects. Body weights were recorded pretest, Day 7 and at termination.

Post Mortem - All animals were humanely sacrificed using CO2 following study termination and were examined for gross pathology.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 1 000 mg/kg bw

Based on:

test mat.

Mortality:

All six rabbits survived the 1000 mg/kg dermal application.

Clinical signs:

Erythema and edema were absent at 24 hour post-dose, Day 7 and at study termination.
One female animal briefly had diarrhea and few feces, otherwise no abnormal physical signs were observed.

Body weight:

Four out of six animals experienced body weight gain by Day 14; one female animal's weight
remained the same, another female animal lost weight by Day 7 and gained by Day 14.

Gross pathology:

The gross necropsies of all animals revealed no observable abnormalities.

Applicant's summary and conclusion

Conclusions:

The LD50 of Compound 3030577, is greater than 1000 mg/kg of body weight in rabbits. The test article is not a poisonous material as defined in 49 CFR 173.132 (a)(1)(ii). Therefore, no Packing Group Assignment is required. The GHS Classification is Not classified. 

Executive summary:

Objective: To determine by dermal exposure if a substance is a poisonous material and, if so, to assign the substance to the applicable packing group category as defined in 49 CFR 173.132 (a)(1)(ii) and 173.133(a)(1). This study was designed to comply with the standards set forth in 49 CFR 173.132(b)(2). The test article is assigned to a toxic category based on the mortality results and significant clinical signs of toxicity up to the Category 4 value tested according to Globally Harmonized System of Classification and Labeling of Chemicals (GHS). 

Method Synopsis: Three healthy male and three healthy female New Zealand White rabbits were dosed dermally with Compound 3030577 at 1000 mg/kg of body weight. The test article was kept in contact with the skin for 24 hours. Dermal responses were recorded 24 hours postdose and on Days 7 and 14. Animals were observed for mortality, toxicity and pharmacological effects at 1 and 2 hours postdose and once daily for 14 days. Body weights were recorded pretest, Day 7 and at death or termination in the survivors. All animals were examined for gross pathology.

Summary: All six rabbits survived the 1000 mg/kg dermal application. One female animal briefly had diarrhea and few feces, otherwise no abnormal physical signs were observed. Erythema and edema were absent at 24 hour postdose, Day 7 and at study termination. Four out of six animals experienced body weight gain by Day 14; one female animal's weight remained the same, another female animal lost weight by Day 7 and gained by Day 14. The gross necropsies of all animals revealed no observable abnormalities.

Conclusion: The LD50 of Compound 3030577, is greater than 1000 mg/kg of body weight in rabbits. The test article is not a poisonous material as defined in 49 CFR 173.132 (a)(1)(ii). Therefore, no Packing Group Assignment is required. The GHS Classification is Not classified.