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

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10 Okt 2016 - 30 Nov 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

2009

GLP compliance:

yes

Limit test:

no

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

Test material form:

liquid: viscous

Test animals

Species:

rat

Strain:

Wistar

Remarks:

RccHan:WIST

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Envigo RMS (UK) Limited, Oxon, UK
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 to 12 weeks old
- Weight at study initiation: 200 g to 350 g.
- Fasting period before study: no
- Housing: In groups of five by sex in solid-floor polypropylene cages with stainless steel lids, furnished with softwood flakes .
- Diet: ad libitum except during exposure
- Water: ad libitum except during exposure
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25 °C
- Humidity (%): 30 to 70%
- Air changes (per hr): at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours continuous light and 12 hours darkness

Administration / exposure

Route of administration:

inhalation: aerosol

Vehicle:

other: ethanol

No. of animals per sex per dose:

5 females and 5 males

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were observed for clinical signs at hourly intervals during exposure, immediately on removal from the restraining tubes at the end of exposure, 1 hour after termination of exposure and subsequently once daily for 14 days.
- Necropsy of survivors performed: yes
- Individual body weights were recorded on arrival, prior to treatment on the day of exposure (Day 0) and on Days 1, 3, 7 and 14.

Results and discussion

Preliminary study:

Prior to the inhalation phase of the study, the non-volatile component of the test item formulation was determined by adding a small, known amount of test item to glass fiber filters and recording their weights. The mean non-volatile component was found to be 52.16 % (n= l0).

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.04 mg/L air

Based on:

test mat.

Mortality:

No mortality occured.

Clinical signs:

other: see section 'Any other information on results'

Body weight:

- other body weight observations: Four male and four female animals exhibited body weight losses or no gain in body weight on Day 1 post-exposure. With the exception of two female animals which exhibited no gain in body weight from Days 1 to 3 post-exposure and a further female animal which exhibited body weight loss from Days 3 to 7 post-exposure, body weight gains were noted throughout the remainder of the recovery period.

Gross pathology:

No macroscopic abnormalities were detected amongst animals at necropsy.

Any other information on results incl. tables

Clinical signs: Hunched posture and pilo-erection and wet fur are considered to be associated with the restraint procedure, during exposure and for short periods on removal from the chamber following 4 hour inhalation studies. During exposure, all animals exhibited decreased respiratory rate. On removal from the chamber and one hour post-exposure, all animals exhibited decreased respiratory rate and ataxia. One day after exposure, significant observations noted in all animals included; hunched posture and pilo-erection. All animals recovered to appear normal on Day 2 post-exposure.

Applicant's summary and conclusion

Interpretation of results:

other: Not harmful

Remarks:

in accordance with EU CLP (EC no 1272/2008 and its amendments)

Conclusions:

The substance has an LC50 of > 5.04 mg/L in an OECD TG 403 test.

Executive summary:

The substance is tested in an acute toxicity inhalation test (OECD TG 403, GLP) on a group of five male and five female rats (nose only) exposed to an achieved aerosol atmosphere of a formulation of the test item with ethanol 50:50 w/w% for four hours at a dose of 5.04 mg/L (nominal 12.07 mg/L). The exposure was followed by a 14 -day observation period. No mortality occurred during the study, and no adverse clinical signs related to the test item were observed. Bodyweights were observed and remained normal. Macroscopy did not reveal any treatment related changes. The LC50 (4h) result in >5.04 mg/L.