1-(5,6,7,8-tetrahydro-3,5,5,6,8,8-hexamethyl-2-naphthyl)ethan-1-one

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

7 June 1977 - 12 August 1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: This study was conducted prior to GLP and OECD guidelines, but was according to acceptable procedures at that time.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1977

Report date:

1977

Materials and methods

Principles of method if other than guideline:

Sprague-Dawley rats were administered AHTN in absolute ethanol (or undiluted) by dermal application to the shaved skin, and were observed for mortality and clinical effects immediately after the dosing at 1, 4, and 24 hours, and also once daily thereafter for a total of 7 days.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1-(5,6,7,8-tetrahydro-3,5,5,6,8,8-hexamethyl-2-naphthyl)ethan-1-one

EC Number:

216-133-4

EC Name:

1-(5,6,7,8-tetrahydro-3,5,5,6,8,8-hexamethyl-2-naphthyl)ethan-1-one

Cas Number:

1506-02-1

Molecular formula:

C18H26O

IUPAC Name:

1-(5,6,7,8-tetrahydro-3,5,5,6,8,8-hexamethyl-2-naphthyl)ethan-1-one

Details on test material:

Fixolide

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

Initial body weight ranged from 108 to 197 grams, and the animals were fasted overnight prior to dosing.

Administration / exposure

Type of coverage:

not specified

Vehicle:

ethanol

Details on dermal exposure:

AHTN was administered by gentle inunction to the shaved skin of 5 groups of five female rats

Duration of exposure:

single administration of dose

Doses:

0.5 to 10 g/kg

No. of animals per sex per dose:

5 (5 groups of 5 animals)

Control animals:

no

Statistics:

Mortality data was analyzed statistically, utilising the tables of Horn, H.J., Biometrics 12, 311, 1956.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

7 940 mg/kg bw

95% CL:

4 890 - 12 900

Remarks on result:

other: Assuming all dead at 21500 mg/kg.

Any other information on results incl. tables

Major necropsy findings: animals found dead exhibited the effects expected at their respecive stages of autolysis; all other animals exhibited no remarkable necroscopy findings.

Table 1: Mortality data and toxic effects of Fixolide tested on acute dermal toxicity on rats.

Dose	Concentration	Time of death
g/kg bw	% in ethanol	Immediate	1-24 h.	24-48h.
0.464	10	0/5	0/5	0/5
1.000	10	0/5	0/5	1/5
2.150	10	0/5	0/5	0/5
4.640	20	0/5	0/5	1/5
10.000	40	0/5	0/5	3/5

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

LD 50 AHTN = 7940 mg/kg, which is larger than the upper limit for classification dermal toxicity (i.e. 2000 mg/kg).

Executive summary:

Groups of 5 female rats were fasted overnight prior to the experiment, and the test material in absolute ethanol was applied to the shaved skin of the animals. Observations for mortality and clinical effects were conducted immediately after the dosing at 1, 4, and 24 hours, and also once daily thereafter for a total of 7 days. Gross necropsy was conducted on all animals (those that died or were sacrificed at the end of the study). The LD50 value was 7.94 g/kg. Animals found dead exhibited the effects expected at their respective stages of autolysis; all other animals exhibited no remarkable necropsy findings.