1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylindeno[5,6-c]pyran

Acute Toxicity: other routes

Administrative data

Endpoint:

acute toxicity: other routes

Type of information:

experimental study

Adequacy of study:

other information

Study period:

From 7 JUNE 1977 to 12 AUG 1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: This study was carried out prior to GLP and OECD guidelines but was conducted according to acceptable procedures at the time.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1977

Materials and methods

Test guideline

Qualifier:

no guideline available

Guideline:

other: The followed procedure is similar to OECD 401/402, however the application is done by intraperitoneal injection

Deviations:

not specified

Principles of method if other than guideline:

Groups of five female rats (Charles River Sprague Dawley - weighing 106-155 g) were dosed with Galaxolide 50 (65% HHCB in DEP) by intraperitoneal injection at different doses and observed for 7 days. This study was conducted prior to GLP and OECD guidelines but was conducted according to acceptable procedure at the time.

GLP compliance:

not specified

Remarks:

This study was prior to GLP and OECD guidelines but was conducted according to acceptable procedures at the time.

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylindeno[5,6-c]pyran

EC Number:

214-946-9

EC Name:

1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylindeno[5,6-c]pyran

Cas Number:

1222-05-5

Molecular formula:

C18H26O

IUPAC Name:

4,6,6,7,8,8-hexamethyl-1H,3H,4H,6H,7H,8H-indeno[5,6-c]pyran

Details on test material:

- Name of test material (as cited int he study report): Galaxolide 50
- Date received: 7/15/77
- Physical state: A clear liquid
- Lot/Batch No.: SG-087-2030
- Purity: Assumed 50% active

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

Initial bodyweight 106-155 g

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

unchanged (no vehicle)

Doses:

0.1, 0.215, 1.0 and 4.64 g/kg bw Galaxolide 50, equivalent to 0.065, 0.14, 0.65 and 3.0 g/kg bw HHCB.

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: Immediately after dosing at one, four and 24 hrs and once daily thereafter for at total 7 days.
- Necropsy of survivors performed: yes

Statistics:

Mortality data was analyzed statistically, utilizing the tables of Horn, HJ. Biometrics 12, 311, 1956.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

3 160 mg/kg bw

Remarks on result:

other: The LD50 was 1.58 g/kg BW expressed as HHCB equivalents

Mortality:

4/5 animals treated at the high dose (4.64 g/kg bw Galaxolide 50) were found dead at 24h. The remaining animal treated with this dose was found dead the next day. There were no deaths at the dose of 1.0 g/kg bw.

Clinical signs:

At 1.0 g/kg bw Galaxolide 50, 3 animals were observed to be in a depressed condition within two hours of dosing but returned to normal at 24h. Lethargy and depression were observed in 4/5 animals at 4.64 g/kg bw Galaxolide within 2 hrs. The remaining animal was prostate at 24 hr.

Gross pathology:

Animals found dead exhibited the effects expected at their respective stages of autolysis; all other animals exhibited no remarkable necropsy findings.

Any other information on results incl. tables

Table 1: mortality data       

		Time of death	Time of death	Time of death
Dose (g/kg)	Concentration (%)	Immediate	1 -24 hrs	2 -7 days
0.1	100	0/5	0/5	0/5
0.215	100	0/5	0/5	0/5
1	100	0/5	0/5	0/5
4.64	100	0/5	4/5	4/5

Applicant's summary and conclusion

Conclusions:

The acute intraperitioneal toxicity of HHCB is low. There is no need to classify HHCB for acute toxicity.

Executive summary:

Groups of five female rats (Charles River Sprague Dawley – weighing 106-155 g) were dosed with Galaxolide 50 (65% HHCB in DEP) by intraperitoneal injection at doses of 0.1, 0.215, 1.0 or 4.64 g/kg bw, (equivalent to 0.065, 0.14, 0.65 or 3.0 g/kg bw HHCB) and observed for 7 days. At 1.0 g/kg, 3 animals were observed to be in a depressed condition within two hr of dosing but returned to normal at 24 hr. There were no deaths at this dose. Lethargy and depression were observed in 4/5 animals at the high dose within 2 hr and all were found dead at 24 hr. The remaining animal was prostate at 24 hr and found dead the next day. Based on these observations an IP LD₅₀of 3.16 g/kg bw (equivalent to 2.1 g/kg bw HHCB) was calculated. This study was conducted prior to GLP and OECD guidelines but was conducted according to acceptable procedure at the time.