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

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

9 August 1985 - 23 August 1985

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in accordance with GLP requirements and OECD 401 method.

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

The variation in volume of dosing; that recommendation was not part of that guideline.

GLP compliance:

yes

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:

244-240-6

EC Name:

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

Cas Number:

21145-77-7

Molecular formula:

C18H26O

IUPAC Name:

1-(3,5,5,6,8,8-hexamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)ethan-1-one

Details on test material:

- Name of test material (as cited in study report): AHTN (Tonalid)
- Substance type: pure active substance
- Physical state:pure active substance dissolved in isopropyl myristate

Test animals

Species:

rat

Strain:

other: Cpb:Wu;Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Young adult, SPF—bred albino rats (Cpb:Wu;Wistar random) were used. They were obtained from the Central Institute for the Breeding of Laboratory Animals TNO, Zeist, the Netherlands. The body weights of the males varied from 245 to 283 g, those of the females from 162 to 187 g. The rats were kept under the environmental conditions of the Institute’s animal house for 1 week prior to the test.
Species: albino ratis, male: weight 245-283 g and female: weight 162-187 g.Test conditions: temperature: 22 =/-2 degreesCelsius. Relative humidity; 40-60 % 12 hours light/12 hours dark. Food: cereal-based diet.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: isopropyl myristate (IPM)

Doses:

17.5% Tonalid in IPM. Dose: 4.00, 4.80, 5.76, 6.91, 8.29 ml/kg body weight euivalent to 700, 840, 1008, 1209, 1451 g/kg body weight.

No. of animals per sex per dose:

10 (5 male and 5 female)

Control animals:

no

Statistics:

The LD5O was calculated according to the method of Weil, C.W., Biometrics 8 (1952) 249-263

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

920 mg/kg bw

95% CL:

> 795 - < 1 066

Mortality:

Deaths occurred between 6 hours and 8 days after dosing.

Clinical signs:

other: Within a few hours after dosing the rats showed sluggishness and piloerection. - Later on haematuria was observed until 2 days after treatment. After a few days, moreover, encrustations around eyes and nostrils, and signs of’ emaciation were observed. The

Gross pathology:

Macroscopic examination at autopsy of the rats that died in the first few post—treatment days revealed blood—stained urine in the bladder of all rats. In the rats that died thereafter and in those that survived the observation period no treatment—related gross alterations were found.

Any other information on results incl. tables

Table 1 Body weight and mortality rate in rats after a single oral dose administration in rats

	Bodyweights on day (g)						Mortality
Dose	Males			Females			Males	Females
mg/kg bw	0 days	7 days	14 days	0 days	7 days	14 days
700	268	280	315	172	171	191	1/5	0/5
840	254	212	273	170	157	170	4/5	0/5
1008	266	235	287	178	150	196	3/5	4/5
1209	257	250	304	174	152	175	4/5	3/5
1451	260	-	-	173	-	-	5/5	5/5

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

After treatment, the rats showed sluggishness, piloerection, haematuria, encrustations around eyes and nostrils & signs of emaciation. Deaths occurred between 6 hours and 8 days after treatment. The oral LD50 of Tonalid was found to be 920 mg per kg body weight with 795 and 1066 as the 95% confidence limits.

Executive summary:

Groups of five male and five female young adult albino rats were administered by gavage 4.00, 4.80, 5.76, 6.91 or 8.29 ml/kg bw of a 17.5% (w/v) solution of AHTN (Tonalid®; purity =98%; equivalent to doses of 700, 840, 1008, 1209 and 1451 mg/kg bw AHTN) in isopropyl myristate and observed for 14 days. Within a few hours, signs of sluggishness and piloerection were seen. Later on haematuria, encrustrations around eyes and nostrils and signs of emaciation were observed. Death occurred between 6 hours and 8 days of dosing at which time survivors recovered gradually looking healthy at the end of the observation period. Macroscopic examination at autopsy of the rats that died in the first few days revealed blood stained urine in the bladder. No other treatment-related gross alterations were seen in these or other animals. An LD50 of 920 mg/kg bw was calculated.

 

Source: EU Risk Asssessment Report AHTN, Luxembourg, Office for Official Publications of the European Communities, ECB (May 2008)