Isopropylcyclohexane

Endpoint summary

Description of key information

Acute oral toxcitity study revealed LD50 of greater than 10000 mg/kg bw in rats for isopropylcyclohexane. Furthermore acute inhalation toxicity study was conducted in rats showing an LC50 of greater than 5.04 mg/l for isopropylcyclohexane. Dermal acute toxicity study is not available for this substance.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1983-02-21 to 1983-03-07

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1981

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Strain: Wistar (Bor: WISW (SPF TNO))
- Source: Winkelmann, Borchen (Germany)
- Weight at study initiation: females 122 g, males 139 g (mean) Environmental conditions:
- Feed: R 10 complete feed for rats (Ssniff, Soest; Germany)
- Water: tap water ad libitum
- Room temperature: 20°C (+/- 1°C)
- Humidity: 60% (+/- 5%)
- Air change: 15 times per hour
- Illumination: 12 hour light/dark rhythm

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

- undiluted application
- Single dose after 16 h of fasting
- Concentration: 10 ml/kg

Doses:

10 000 mg/kg bw (gavage),

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Post dose observation period: 14 days
EXAMINATIONS:
- body weight: before and on days 1, 7, 14 after treatment
- clinical signs: up to 6 hours after treatment, then daily
- gross pathology at the end of investigation

Statistics:

not neccessary

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 10 000 mg/kg bw

Mortality:

no mortality

Clinical signs:

other: About 45 minutes after adminstration the animals showed ruffeld fur, staggering, prone position, Straub's phenomenon, slight sedation and ataxia. Signs of toxicity had disappeared after 24 hours.

Gross pathology:

no findings

Other findings:

no further information

no further remarks

Conclusions:

In a determination of the acute oral toxicity on male and female rats it was found that the LD50 of the test item isopropylcyclohexane is greater than 10000 mg/kg body weight. Under the conditions of this study Isopropylcyclohexane is practically nontoxic after oral application in rats.

Executive summary:

The test item was given to rats by oral administration to obtain information on the toxicity, in particular lethality, of the test item.

Isopropylcyclohexane was administrated oral to 5 male and 5 female WISTAR rats. There was no mortality and no influence on the increase in body weight. About 45 minutes after adminstration the animals showed ruffeld fur, staggering, prone position, Straub's phenomenon, slight sedation and ataxia. Signs of toxicity has disappeared after 24 hours. Dissection at the end of the experiment showed no findings.

Under the conditions of this study the acute toxicity after oral application is greater than 10000 mg/kg bw. Therefore, isopropylcyclohexane is practically nontoxic after oral application in rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

10 000 mg/kg bw

Quality of whole database:

The study is a guideline study with Klimisch score 1 (reliable without restriction).

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2011-10-04 to 2011-11-21

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

2009

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Version / remarks:

2008

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Version / remarks:

1998

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Rattus norvegicus

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ORGANISMS: 
- Strain: Rattus norvegicus) / CD / Crl: CD(SD)
- Source: Charles River Laboratories, 97633 Sulzfeld, Germany
- Age: males: approx. 7 weeks, females: approx. 9 weeks
- Weight at study initiation: males: 241 - 245 g, females: 220 - 255 g
- Number of animals: 3 males and 3 females
- Fasting period before study: 16 hours
- Housing: groups of two or three
- Diet: ad libitum, ssniff R/m-H V 1534
- Water: ad libitum, tab water
- Acclimatisation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +/- 3 °C
- Humidity (%): 55 + / - 15 %
- Photoperiod (hrs dark / hrs light): 12 hours darkness, 12 hours artifical light

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: compressed filtered air

Mass median aerodynamic diameter (MMAD):

2.268 µm

Geometric standard deviation (GSD):

2.64

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Type of exposure: nose-only, using a dynamic inhalation apparatus, air changes >/= 12/h
- Method of holding animals in test chamber (volume 40 l): separatley in Pyrex tubes at the edge of the chamber in radial position
- Source of air: compressed filtered air
- Method of conditioning air: manometer and air-flow meter (ROTA Yokogawa), flow rates checked once per hour and corrected if necessary
- Oxygen content: 21 %, determined at beginning and end of exposure, Carbon dioxide concentration did not exceed 1 %
- Type or preparation of particles: The aerosol of the test item was obtained using a spray-jet. The spray-jet was fed with compressed air (5.0 bar)
from a compressor and with the test item using a TSE infusion pump. At the bottom of the exposure chamber, the air was sucked off at a lower rate than created by the spray-jet in order to produce a homogenous distribution and a positive pressure in the exposure chamber (inflow 900 L/h,
outflow 800 L/h).
- Analysis of the aerosol concentration: The actual aerosol concentration in the inhalation chamber was measured gravimetrically with an air sample
filter (Minisart SM 17598 0.45 µm) and pump (Vacuubrand, MZ 2C ) controlled by a rotameter. Dust samples were taken once every hour during the exposure
- Method of particle size distribution: An analysis of the particle size distribution was carried out twice during the exposure period using a cascade
impactor according to MAY . The impactor is a device that classifies particles present in a sample of air or gas into known size ranges. It does this by drawing the air sample through a cascade of progressively finer nozzles. The air jets from these nozzles impact on pre-weighed plane sampling
surfaces (slides). The aerosol from the exposure chamber was drawn through the cascade impactor for 5 minutes at a constant flow rate of 5 L/min. The slides were removed from the impactor and weighed on an analytical balance (SARTORIUS, type 1601 004, precision 0.1 mg). The mass median aerodynamic diameter (MMAD) was determined as 2.268 µm. The Geometric Standard Deviation (GSD) of the MMAD was calculated as 2.64.
- Temperature, humidity: T: 20.4 +/- 0.08°C, H: 60.9 % +/- 0.15 %, measured once every hour
TEST ATMOSPHERE
- Concentrations: 5.04 mg/l 
Air flow entrance (L/h): 900
Air flow exit (L/h): 800
Air change (changes per hour): 22.5

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Gravimetric determination of aerosol concentrations with an air sample filter. Dust samples were taken once every hour during the exposure.

Duration of exposure:

4 h

Concentrations:

gravimetric aerosol concentration of 5.04±0.11 mg Isopropylcyclohexane/L air was measured at the animals’ nose.

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

EXAMINATIONS: 
- Post dose observation period: 14 days
- body weights: before,  7 and 14 days after treatment   
- mortality: once per hour during, and once after treatment on day of  exposure;  thereafter twice daily
- clinical signs: during and following exposure, observations were made and recorded systematicallye,  at least twice daily until all symptoms
subsided, thereafter each working day
- Necropsy: all animals (macroscopic) when found dead or at terminal  sacrifice. In addition, the weight of the lungs was determined.

Statistics:

not necessary

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.04 mg/L air

Based on:

act. ingr.

Exp. duration:

4 h

Mortality:

No animal died prematurely.

Clinical signs:

other: slight ataxia, slightly reduced muscle tone and slight dyspnoea immediately until 60 minutes or 3 hours after end of exposure

Body weight:

All animals gained the expected body weight.

Gross pathology:

None findings

Other findings:

no other findings

The mean actual exposure concentration, MMAD and GSD of Isopropylcyclohexane were as follows:

nominal concentration	gravimetric concentration (actual)	mass median aerodynamic diameter (MMAD)	geometric standard deviation (GSD)
[µL/L air]	[mg/L air]	[µm]
11.11	5.04	2.268	2.64

Conclusions:

Under the present test conditions, LC50-value for CD rats following inhalation of Isopropylcyclohexane for 4 hours was determined as follows
(actual concentration): LC50: exceeding 5.04 mg Isopropylcyclohexane/L air.

Executive summary:

The aim of the present experiment was to obtain information on the acute toxicity and LC₅₀, following a single 4-hour inhalation exposure in an acute inhalation study in rats.

Rats were exposed to isopropylcyclohexane at a concentration of 5.04±0.11 mg isopropylcyclohexane/L air for 4 hours by inhalation using a dynamic nose-only exposure chamber. The aerosol was generated with the aid of a spray-jet.

In the inhalation chamber, close to the animals' noses, the generated aerosol particulates had a mass median aerodynamic diameter (MMAD) of 2.268 µm as deter­mined with a cascade impactor. The Geometric Standard Deviation (GSD) of the MMAD was calculated as 2.64.

Under the present test conditions, a 4-hour inhalation of 5.04 mg isopropylcyclohexane/L air revealed slight ataxia, slightly reduced muscle tone and slight dyspnoea immediately until 60 minutes or 3 hours after end of exposure. No animal died prematurely. No pathological findings were noted at necropsy. All animals gained the expected body weight.

LC₅₀:     >5.04 mg/L air for both sexes combined

According to the EC Regulation 1272/2008 and subsequent regulationson classification, labelling and packaging of substances and mixtures, isopropylcyclohexane does not require classification for acute inhalation toxicity. 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

5 040 mg/m³ air

Quality of whole database:

The study is a guideline study with Klimisch score 1 (reliable without restriction)

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity study revealed LD50 of greater than 10000 mg/kg bw in rats for isopropylcyclohexane. There was no mortality observed. About 45 minutes after adminstration the animals showed ruffeld fur, staggering, prone position, Straub's phenomenon, slight sedation and ataxia. Signs of toxicity had disappeared after 24 hours.

Furthermore acute inhalation toxicity study was conducted in rats showing an LC50 of greater than 5.04 mg/L for isopropylcyclohexane.

4-hour inhalation revealed slight ataxia, slightly reduced muscle tone and slight dyspnoea immediately until 60 minutes or 3 hours after end of exposure. No animal died prematurely. No pathological findings were noted at necropsy.

Dermal acute toxicity study is not available for this substance

Justification for selection of acute toxicity – oral endpoint
Only one study available.

Justification for selection of acute toxicity – inhalation endpoint
Only one study available.

Justification for selection of acute toxicity – dermal endpoint
Acute dermal toxicity study not needed because inhalation exposure is expected to be the relevant route of exposure

Justification for classification or non-classification

Based on the results of the oral and inhalation acute studies in rats and according to the EC Regulation 1272/2008 and subsequent regulations on classification, labelling and packaging of substances and mixtures, isopropylcyclohexane does not require to be classified.