1-ethynylcyclohexanol

Endpoint summary

Description of key information

The LD50 values derived from the key studies were: LD50 (oral, rat) 600 mg/kg bw and LD50 (dermal, rat) 1000 mg/kg bw.

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:

1962

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable publication which meets basic scientific principles.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

not specified

Principles of method if other than guideline:

Method: other: Smyth/Carpenter

GLP compliance:

no

Remarks:

prior to GLP

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Carworth-Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Colony of the Mellon Institute of Industrial Research (Pittsburgh, Pennsylvania, USA) (in-house breeding)
- Age at study initiation: 4-5 weeks old
- Weight at study initiation: 90 to 120 g
- Fasting period before study: no
- Diet: Rockland rat diet complete

Route of administration:

oral: gavage

Vehicle:

other: water, corn oil or 1 % Tergitol Penetrant 7

Details on oral exposure:

(Dose volume: 1 to 10 mL/rat, oral gavage)

Doses:

Logarithmic series of dose levels

No. of animals per sex per dose:

5 animals

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days

Statistics:

The most probable LD50 was estimated by the methods of Thompson (1947) and Weil (1952).

Sex:

male

Dose descriptor:

LD50

Effect level:

600 mg/kg bw

Remarks on result:

other: reported as 0.60 mL/kg bw

Sex:

male

Dose descriptor:

LD50

Effect level:

>= 0.43 - <= 0.84 mL/kg bw

Mortality:

Death occurred within 14 days, no detailed information provided.

Clinical signs:

other: No information provided

Gross pathology:

No information provided

single oral gavage, deaths within 14 days. Limits of +/- 1.96 standard deviation using the method of Thompson: 430 - 840 mg/kg bw. Original LD50 given as 0.6 mL/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

600 mg/kg bw

Quality of whole database:

Acceptable publication.

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:

1962

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable publication which meets basic scientific principles.

Principles of method if other than guideline:

Method: other: Smyth/Carpenter

GLP compliance:

no

Remarks:

prior to GLP

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

Name of the test material: 1-Ethynylcyclohexanol

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

INHALATION EXPOSURE AND TEST ATMOSPHERE
Concentrated vapor inhalation consisted of subjecting animals to a flowing stream of vapor-ladened air prepared by various styles of proportioning pumps. The vapor-air mixture was generated by passing 2.5 Liters/minute of dried air at room temperature through a fritted glass disc immersed to a depth of at least one inch in approximately 50 mL of the test chemical contained in a gas-washing bottle.

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

8 h

Concentrations:

Logarithmic series of vapor concentrations

No. of animals per sex per dose:

6 animals (male or female)

Control animals:

no

Details on study design:

INHALATION EXPOSURE TIMES
Rats were rapidly introduced by means of a drawer-type cage designed to minimize vapor loss. Inhalation of metered vapor concentrations were conducted were usually of four hours' duration unless slight toxicity enforces an eight-hour period (maximum period). For inhalation periods of ten, five and two minutes in duration, a static technique is used whereby 50 to 100 grams of material, spread over a shallow tray 200 square inches in area, is placed in a 120-Liter sealed chamber for at least 24 hours. This method was also employed for mixtures of liquids and for solids. Nominal concentrations were not analytically verified. They were in an essentially logarithmic series with a factor of two with a ratio of two extending from one-fourth to eight hours.

OBSERVATIONS
The period which permitted all rats to survive the two-week observation period was noticed. The concentration yielding fractional mortality was noticed. Where no fractional mortality was observed, usually both the concentration yielding no mortality and that yielding complete mortality were indicated.

Dose descriptor:

LC0

Based on:

test mat.

Exp. duration:

8 h

Remarks on result:

other: saturated atmosphere

Mortality:

No mortality was observed.

Clinical signs:

other: No information provided

Body weight:

No information provided

Gross pathology:

No information provided

No mortality was observed when 6 rats were exposed for 8 hours to an atmosphere that had been saturated at room temperature with the volatile part of the compound.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

Acceptable publication.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1962

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable publication which meets basic scientific principles.

Principles of method if other than guideline:

Method: other: Smyth/Carpenter

GLP compliance:

no

Remarks:

prior to GLP

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: young adult (based on body weight)
- Weight at study initiation: 2.5 - 3.5 kg

Type of coverage:

occlusive

Vehicle:

not specified

Details on dermal exposure:

Penetration of rabbit skin was estimated by the one-day cuff method of Draize and associates. The fur was closely clipped over the entire trunk, and the dose retained beneath an impervious plastic film.

Duration of exposure:

24 hours

Doses:

up to 20 mL/kg bw

No. of animals per sex per dose:

4 animals

Control animals:

not specified

Details on study design:

After 24 hours contact the film was removed. Mortality was considered complete after 14 additional days.
- Duration of observation period following administration: 14 days

Statistics:

The most probable LD50 was estimated by the methods of Thompson (1947) and Weil (1952).

Sex:

male

Dose descriptor:

LD50

Effect level:

1 000 mg/kg bw

Remarks on result:

other: reported as 1.00 mL/kg bw

Sex:

male

Dose descriptor:

LD50

Effect level:

>= 0.68 - <= 1.48 mL/kg bw

Mortality:

Death occurred within 14 days, no detailed information provided.

Clinical signs:

other: No information provided

Gross pathology:

No information provided

24 h exposure time, deaths within 14 days. Limits of +/- 1.96 standard deviation using the method of Thompson: 680 - 1480 mg/kg bw. Original LD50 given as 1.0 mL/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 000 mg/kg bw

Quality of whole database:

Acceptable publication.

Additional information

Acute toxicity: oral
In a single dose study (Smyth et al., 1962), acute oral toxicity of 1-Ethinylcyclohexanol was estimated by oral gavage in 5 male Carworth-Wistar rats per dose level using a logarithmic series of doses. 1-Ethinylcyclohexanol was diluted with a vehicle when necessary (to bring the dose volume to 1 to 10 mL per rat). 14 days after dosing, mortality was considered as complete. Oral administration of 1-Ethinylcyclohexanol to female rats resulted in a LD50 value of 600 mg/kg bw. This study is classified as acceptable (key study).

Additionally, in a reliable study published by U.S. EPA (1992) a LD50 value of 1150 mg/kg bw was listed. Furthermore, in a single dose study (BASF, 1952) a LD50 value >300 mg/kg bw was determined. Both studies are classified as acceptable (supporting studies).

 

Acute toxicity: inhalation

In an acute inhalation toxicity study based on a concentrated vapor inhalation method (Smyth et al., 1962), six albino rats were exposed to logarithmic series of vapor concentrations of 1-Ethynylcyclohexanol for periods up to 8 hours and observed for 14 days. An 8 hours exposure to a flowing stream of vapor-loadened air with the test substance resulted in no mortality. Thus, inhalation of a concentrated vapor of 1-Ethynylcyclohexanol did not pose an acute risk to animal’s health. This acute inhalation toxicity study is classified as acceptable (key study).

 

Acute toxicity: dermal

In an acute dermal toxicity study (Smyth et al., 1962), four male rabbits were exposed to 1-Ethynylcyclohexanol. The test material was applied in a single dose to the clipped skin of the entire trunk beneath an impervious plastic film. After 24 hour exposure the film was removed, and mortality was considered complete after 14 additional days of observation. Death occurred within the observation period. Limits of ±1.96 standard deviation using the method of Thompson were 0.68 – 1.48 mL/kg bw. The LD50 determined in this study was 1.0 mL/kg bw (corresponding to ~1000 mg/kg bw). This study is classified as acceptable. It satisfies the guideline requirement for an acute dermal study according OECD 402 in principle (key study).

Justification for selection of acute toxicity – oral endpoint
The key study was selected.

Justification for selection of acute toxicity – inhalation endpoint
The key study was selected.

Justification for selection of acute toxicity – dermal endpoint
The key study was selected.

Justification for classification or non-classification

Based on the results of the oral acute toxicity study, 1-Ethynylcyclohexanol is classified as Xn, R22 (harmful if swallowed) according to the criteria of EU Directive 67/548/EEC and as Cat. 4, H302 (harmful if swallowed) according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No 1272/2008.

 

Based on the results of the dermal acute toxicity study, 1-Ethynylcyclohexanol is classified as Xn, R21 (harmful in contact with skin) according to the criteria of EU Directive 67/548/EEC and as Cat. 3, H311 (toxic in contact with skin) according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No 1272/2008.