2-phenylhexanenitrile

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 17 January 1995 and 31 January 1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-phenylhexanenitrile

EC Number:

423-460-8

EC Name:

2-phenylhexanenitrile

Cas Number:

3508-98-3

Molecular formula:

C12 H15 N

IUPAC Name:

2-phenylhexanenitrile

Test material form:

liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Equal numbers of healthy male and female CD rats of Sprague-Dawley origin (Hsd/Ola:SpragueDawley(CD)) were obtained from Harlan Olac Ltd., Bicester, Oxon, England.
They were in the weight range of 215 to 241 g and approximately seven to ten weeks of age prior to dosing (Day 1). All the rats were acclimatised to the experimental environment for a period of five days prior to the start of the study.
The rats were allocated without conscious bias to cages within the treatment groups. They were housed individually in metal cages with wire mesh floors in Building R14 Room 6.
A standard laboratory rodent diet (Biosure LAD 1) and drinking water were provided ad libitum.
Each batch of diet used for the study was analysed for certain nutrients, possible contaminants and microorganisms .
Results of routine physical and chemical examination of drinking water at source as conducted, usually weekly by the supplier, are made available to Huntingdon Research Centre Ltd. as quarterly summaries.
Animal room temperature was set to achieve a temperature of 22 ± 3°C. Relative humidity was not controlled but was anticipated to be in the range 30 - 70%. Permanent daily recordings of these parameters were made and these are archived with other Department raw data. Any slight deviation in temperature and humidity that may have occurred had no impact on the study in the opinion of the Study Director. Air exchange was maintained at 10 to 15 air changes per hour and lighting controlled by means of a time switch to provide 12 hours of artificial light (0700 - 1900 hours) in each 24-hour period.
Each animal was identified by cage number and ear punching. Each cage was identified by a coloured label displaying the dose level, study schedule number, animal mark and the initials of the Study Director and Home Office license.

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

A group of ten rats (five males and five females) was treated at 2.0 g/kg bodyweight. The test substance was applied by spreading it evenly over the prepared skin

Duration of exposure:

24 hours

Doses:

2.0 g/kg bodyweight.

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

TREATMENT PROCEDURE
A group of ten rats (five males and five females) was treated at 2.0 g/kg bodyweight. One day prior to treatment, hair was removed from the dorso-lumbar region of each rat with electric clippers exposing an area equivalent to approximately 10% of the total body surface. The test substance was applied by spreading it evenly over the prepared skin. The treated area (approximately 50 mm x 50 mm) was then promptly covered with gauze which was held in place with a non-irritative dressing encircled firmly around the trunk. At the end of the 24 hours exposure period, the dressings were carefully removed and the treated area of skin was washed with warm (30° to 40°C) water and blotted dry with absorbent paper. The day of dosing was designated Day 1.

Control animals
No control animals were included in this study.

OBSERVATIONS
- Mortality: Cages of rats were checked at least twice daily for any mortalities.
- Clinical signs: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1 (a period of six hours). On subsequent days animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only). This latter observation was at approximately 16: 30 hours on week days or 11: 30 hours on Saturdays and Sundays. The nature and severity of the clinical signs and time were recorded at each observation. All animals were observed for 14 days after dosing.
- Dermal responses: Local dermal irritation at the treatment site was assessed daily using the following numerical system:

Erythema and Eschar
- No erythema: 0
- Slight erythema: 1
- Well-defined erythema: 2
- Moderate to severe erythema: 3
- Severe erythema (beet redness) to slight eschar formation (injuries in depth): 4

Oedema Formation
- No oedema: 0
- Slight oedema: 1
- Well-defined oedema (edges of area well-defined by definite raising): 2
- Moderate oedema (raised approximately 1 millimetre): 3
- Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure): 4

- Bodyweight: Individual bodyweights were recorded on Days 1 (prior to dosing), 8 and 15. Individual weekly bodyweight changes were calculated.
- Macroscopic examination: All animals were killed on Day 15 by cervical dislocation and were subjected to a macroscopic examination which consisted of opening the abdominal and thoracic cavities. The macroscopIc appearance of all examined tissues was recorded.

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:

There were no deaths following a single dermal application of Salicynalva to a group of ten rats (five males and five females) at a dosage of 2.0 g/kg bodyweight.

Clinical signs:

other: There were no signs of systemic reaction to treatment.

Gross pathology:

No macroscopic abnormalities were observed for animals killed on Day 15.

Other findings:

With the exception of a residual black staining from the test substance on the treatment sites of some animals there were no other dermal changes observed in any animal throughout the dose period (scores of zero for erythema and oedema were recorded for all animals).

Applicant's summary and conclusion

Interpretation of results:

other: not harmful in accordance with EU CLP (EC no 1272/2008 and its amendments)

Conclusions:

The substance has an LD50 of > 2000 mg/kg bw in an OECD TG 402 test

Executive summary:

An OECD TG 402 study was performed to assess the acute dermal toxicity of Salicynalva to the rat. A group of ten rats (five males and five females) was given a single occlusive dermal application of the test substance, as supplied by the sponsor and administered at a dosage of 2.0 g/kg bodyweight, no vehicle was used. All animals were killed and examined macroscopically on Day 15, the end of the observation period. There were no deaths and no signs of systemic reaction to treatment. With the exception of a residual black staining from the test substance on the treatment sites of some animals, there were no other dermal changes observed in any animal throughout the dose period (scores of zero for erythema and oedema were recorded for all animals). Slightly low bodyweight gains were recorded for three males and three females on Day 8, with a similar trend noted for one male and two females on Day 15. In addition, two females showed a slight bodyweight loss on Day 8 and one female showed no bodyweight gain on Day 15. The remaining animals achieved anticipated bodyweight gains throughout the study. No abnormalities were recorded at the macroscopic examination on Day 15. The acute lethal dermal dose to rats of Salicynalva was found to be greater than 2000 mg/kg bodyweight.