1-Propanol, 2-methyl-3-[(1,7,7-trimethylbicyclo[2.2.1]hept-2-yl)oxy]-

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The experimental phase of the study was undertaken between 4 March and 18 March 1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

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:

-

EC Number:

416-210-4

EC Name:

-

Cas Number:

128119-70-0

Molecular formula:

C14H26O2

IUPAC Name:

2-methyl-3-({1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl}oxy)propan-1-ol

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 a reputable supplier.
- They were in the weight range of 220 to 283 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 fourteen days prior to the start of the study.
- The rats were allocated without conscious bias to cages within the treatment group. They were housed individually in metal cages with wire mesh floors in Building R 14 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 micro-organisms.
- 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).
- The mean daily minimum and maximum temperatures of the animal room were 20°C and 22°C respectively and the mean daily relative humidity value was 49% R.H. Air exchange was maintained at 10 to 15 air changes per hour and lighting was controlled by means of a time switch to provide 12 hours of artificial light (0700 - 1900 hours) in each 24 hours period.

Administration / exposure

Type of coverage:

semiocclusive

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. One day prior to treatment hair was removed from the dorso-Iumbar 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.

Duration of exposure:

24 hours

Doses:

2.05 ml/kg (specific gravity 0.975)

No. of animals per sex per dose:

A group of ten rats (five males and five females)

Control animals:

no

Details on study design:

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 seven hours). On subsequent days animals were observed once in the morning and again at the end of the experimental day. This latter observation was at approximately 16.30 hours on week daysor 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 formation: No erythema: 0; Slight erythema: 1; Well-defined erythema: 2; Moderate erythema: 3; Severe erythema (beet redness) to slight: 4; eschar formation (injuries in depth): 5
- 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& 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 folIowing a single dermal application of Bornafix at 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:

DERMAL RESPONSES
Slight erythema with no oedema was observed at the sites of application of the test substance for all rats on Day 2 and in females only on Days 3 and 4.

There were no other dermal changes and irritation had resolved by either Day 3 (males) or Day 5 (females). for full details please see table 1

Any other information on results incl. tables

Table 1 Dermal reactions observed after application of Bornafix

Dose g/kg	Sex	Animal number & ear mark	E = Erythema O = Oedema	Day
				2	3	4	5 To 15
2	M A L E	1 RP	E	1	0	0	0
			O	0	0	0	0
		2 LP	E	1	0	0	0
			O	0	0	0	0
		3 RLP	E	1	0	0	0
			O	0	0	0	0
		4 RIRO	E	1	0	0	0
			O	0	0	0	0
		5 LILO	E	1	0	0	0
			O	0	0	0	0
	F E M A I L	6 RP	E	1	1	1	0
			O	0	0	0	0
		7 LP	E	1	1	1	0
			O	0	0	0	0
		8 RPLP	E	1	1	1	0
			O	0	0	0	0
		9 RIRO	E	1	1	1	0
			O	0	0	0	0
		10 LILO	E	1	1	1	0
			O	0	0	0	0

Table 2 Individual bodyweights (g) of rats dosed dermally with Bornafix

Sex	Dose g/kg	Animal number & ear mark	Bodyweight (g) at
			Day 1	Day 8	Day 15
M A L E	2.0	1 RP	269	314	370
		2 LP	261	293	332
		3 RPLP	264	298	354
		4 RIRO	283	315	367
		5 LILO	277	309	360
F E M A I L	2.0	6 RP	236	242	251
		7 LP	241	255	272
		8 RPLP	245	255	261
		9 RIRO	220	230	244
		10 LILO	252	263	290

Table 3 Individual bodyweight changes (g) of rats dosed dermally with Bornafix

Sex	Dose g/kg	Animal number & ear mark	Bodyweight gains (g) at
			Week 1	Week 2
M A L E	2.0	1 RP	45	56
		2 LP	32	39
		3 RPLP	34	56
		4 RIRO	32	52
		5 LILO	32	51
F E M A I L	2.0	6 RP	6	9
		7 LP	14	17
		8 RPLP	10	6
		9 RIRO	10	14
		10 LILO	11	27

Applicant's summary and conclusion

Interpretation of results:

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

Conclusions:

In an acute dermal toxicity test in male and female rats, an LD50 of > 2000 mg/kg bw was determined.

Executive summary:

A study according to OECD 402 was performed to assess the acute dermal toxicity of Bornafix to the rat. A group of ten rats (five males and five females) was given a single occlusive dermal application of the test substance, at a dose level of 2.0 g/kg bodyweight. 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. Slight erythema with no oedema was observed at the sites of application of the test substance for all rats on Day 2 and in females only on Days 3 and 4. There were no other dermal changes and irritation had resolved by either Day 3 (males) or Day 5 (females). Slightly low bodyweight gains were recorded for four males and four females on Day 8 and in one male and two females on Day 15; the remaining rats achieved anticipated gains on Day 15. All other rats 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 Bornafix was found to be greater than 2.0 g/kg bodyweight.