N-(2-ethylhexyl)-8,9,10-trinorborn-5-ene-2,3-dicarboximide

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17 November 2004 to 22 Mar 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

August 1998

Deviations:

not specified

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

24 February, 1987

Deviations:

not specified

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N-(2-ethylhexyl)-8,9,10-trinorborn-5-ene-2,3-dicarboximide

EC Number:

204-029-1

EC Name:

N-(2-ethylhexyl)-8,9,10-trinorborn-5-ene-2,3-dicarboximide

Cas Number:

113-48-4

Molecular formula:

C17H25NO2

IUPAC Name:

N-(2-ethylhexyl)-8,9,10-trinorborn-5-ene-2,3-dicarboximide

impurity 1

Reference substance name:

(E)-1,4-Bis(2-ethylhexylamino)-2-butene-1,4-dione

Molecular formula:

C20H38N2O2

IUPAC Name:

(E)-1,4-Bis(2-ethylhexylamino)-2-butene-1,4-dione

impurity 2

Reference substance name:

1-(2-ethylhexyl)-1H-pyrrole-2,5-dione

Molecular formula:

C12H19NO2

IUPAC Name:

1-(2-ethylhexyl)-1H-pyrrole-2,5-dione

Test material form:

liquid

Details on test material:

Purity and characterisation analysis conducted on the following sample; Supplier: McLaughlin Gormley King ; Batch Number: AB9500

Specific details on test material used for the study:

MGK 264
Lot No.: AA-7093
Purity: 95.2% MGK 264 (From CofA)

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Description, Identification and Housing
Adult, Hsd: Sprague Dawley® SD® rats were received from Harlan Sprague Dawley, Inc., Indianapolis. IN. Upon receipt, metal ear tags displaying unique identification numbers were used to individually identify the animals. Cage cards displaying at least the study number, animal number and sex were affixed to each cage. The animals were housed individually in suspended stainless steel cages. All housing and care were based on the standards recommended by the Guide for the Care and Use of Laboratory Animals.
Environment, food and water
The animal room temperature and relative humidity ranges were 64-71°F (18-22°C) and 40-61 %. respectively. Environmental control equipment was monitored and adjusted as necessary to minimize fluctuations in the animal room environment. Light timers were set to maintain a 12-hour Iightll2-hour dark cycle and room ventilation was set to produce 10-15 air changes/hour. The animal room temperature and relative humidity were recorded a minimum of once daily. Food and Water provided ad libitum.

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

On the day following clipping of the fur from the dorsal trunk (day 0), the test article was administered dermally to approximately 10% of the body surface area. The four comers of this area were delineated in the clipped area with an indelible marker. The test article was then spread evenly over the delineated test area and held in contact with the skin with an appropriately sized 4-ply porous gauze dressing backed with a plastic wrap which was placed over the gauze dressing (occlusive binding). Removal and ingestion of the test article was prevented by placing an elastic wrap over the trunk and test area. The elastic wrap was further secured with a tape harness on the cranial end of the trunk and then secured with adhesive tape around the trunk at the caudal end.

Duration of exposure:

After an approximate 24-hour exposure period, the binding materials were removed and the corners of the test site were re-delineated using a marker. Residual test article was removed using gauze moistened with deionized water followed by dry gauze.

Doses:

5000 mg/kg

No. of animals per sex per dose:

5 males and 5 females per dose.

Control animals:

no

Details on study design:

The single-dose dermal toxicity of MGK® 264 was evaluated in Sprague Dawley rats. A limit test was performed in which one group of five male and five female rats received a single dermal administration of the test article at a dose of 5000 mg/kg body weight. Following dosing, the limit test rats were observed daily and weighed weekly. A gross necropsy examination was performed on all animals at the time of scheduled euthanasia (day 14).

Statistics:

Data from the limit test were analyzed and an LD50 value estimated as follows:

< 50% Mortality: LD50 was estimated as greater than the administered dose.
= 50% Mortality: LD50 was estimated as equal to the administered dose.
> 50% Mortality: LD50 was estimated as less than the administered dose.

Body weight means and standard deviations were calculated separately for males and females.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

other: LD50 found to be greater than 5000 mg/kg

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality occurred during the limit test.

Mortality:

No mortality occurred during the limit test.

Clinical signs:

Clinical abnormalities observed during the study included transient incidences of dark material around the facial area and ocular discharge. Dermal irritation was noted at the site of test article application.

Body weight:

Body weight gain was noted for all animals during the test period.

Gross pathology:

No gross internal findings were observed at necropsy on study day 14.

Applicant's summary and conclusion

Interpretation of results:

other: No symbol and risk phrases are required according to EEC labelling regulations. (EC 1272/2008)

Conclusions:

The acute dermal lethal dose (LD50) of the test material, in male and female Sprague-Dawley rats was found to be greater than 2000 mg/kg bodyweight. No symbol and risk phrases are required according to EEC labelling regulations. (EC 1272/2008)

Executive summary:

The single-dose dermal toxicity of MGK® 264 was evaluated in Sprague Dawley rats. A limit test was performed in which one group of five male and five female rats received a single dermal administration of the test article at a dose of 5000 mg/kg body weight. Following dosing, the limit test rats were observed daily and weighed weekly. A gross necropsy examination was performed on all animals at the time of scheduled euthanasia (day 14).

No mortality occurred during the limit test.

The acute dermal lethal dose (LD50) of the test material, in male and female Sprague-Dawley rats was found to be greater than 2000 mg/kg bodyweight. No symbol and risk phrases are required according to EEC labelling regulations. (EC 1272/2008)