Ethylcyclohexane

Endpoint summary

Description of key information

Acute oral toxicity:

An acute oral toxicity study was conducted in male and female rats administered a single limit dose of 2000 mg/kg of the test material by gavage. Discolored (light-brown) feces were noted from all animals on the day following dosing. No other abnormal clinical signs were observed during the 14-day observation period. No mortality was observed, and all animals gained weight normally. Treatment-related changes observed at necropsy were limited to minimal hyperkeratosis of the non-glandular gastric mucosa. for all males and three of five females. No other treatment-related changes or signs of organ toxicity were noted at necropsy. In the absence of significant gross organ lesions, other than the obvious signs of gastric irritation, no tissue was collected for histological examination. The acute oral LD50 for this test material was greater than 2000 mg/kg for male and female rats.

Acute dermal toxicity:

A limit dose of 2000 mg/kg was applied to the skin after the hair was removed with an electric clipper. An occlusive wrap was used to hold the test material against the skin for a period of 24 hours, and at the end of exposure, residual test material was washed off with running water.

No treatment-related abnormal clinical signs were evident at any time during the 14-day observation period. On the last day of the observation period, a small wound with a scab was noted on the shoulder of a single male (Rat 745). Since this animal had appeared clinically normal from the day of dosing to Day 13, this wound was not considered related to administration of the test material. No treatment-related changes or signs of organ toxicity were evident at necropsy. In the absence of significant gross organ lesions, no tissue was collected for histological examination. Based on weight gain and survival rate, there was no evidence of percutaneous absorption. The acute dermal LD50 for this test material was greater than 2000 mg/kg for both sexes.

Acute inhalation toxicity: Data from the read-across substance methylcyclohexane is available:

Health Council of the Netherlands:

When rats were exposed to vapour concentrations of 82,000-260,000 mg/m3 (ca. 20,000-62,000 ppm), mortality occurred within 13-70 minutes, animals showing anaesthesia, lethargy, ataxia, and terminal convulsion. Exposure to 11,000 mg/m3 (ca. 2600 ppm), for 6 hours, induced only minor symptoms (lethargy in 3 hours)

CDC:

In mice, a 2-hour LC50 of 41,500 mg/m3 (ca. 10,000 ppm) is reported. No detailed study description is given.

Publication Treon:

In this rabbit study, all the animals died at 59.9 mg/L within 70 min after exposure initiation. LC50 was considered as between 39.6 and 59.9 mg/L. Signs of toxicity at 59.9 mg/L (70 min exposure) included severe convulsions, rapid narcosis, labored breathing, salivation, and conjunctival congestion.

Since it was judged in the SIDS INITIAL ASSESSMENT PROFILE for the Methyl-Ethylcyclohexane Category that the read across from methyl- to ethylcyclohexane is plausible and can be proven by the similarity in structure and physicochemical properties, it is assumed that ethylcyclohexane will behave in a similar manner with respect to acute inhalation toxicity.

Based on the narcotic effects observed in the available studies for methylcyclohexane at high concentration classification of methylcyclohexane according to Regulation (EC) No 1272/2008 as STOT-SE 3 (narcotic effects) is fully justified.

Therefore ethylcyclohexane will be classified as STOT-SE 3 (narcotic effects) too.

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:

1992-01-20 - 1992-04-03

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Specific details on test material used for the study:

SRI1D or Lot I.D. Number: 7482-9A
Physical State and Appearance: Colorless liquid

Species:

rat

Strain:

other: CD(SD)BR VAF/Plus

Sex:

male/female

Details on test animals or test system and environmental conditions:

Housing:
All animals were individually housed in suspended, stainless-steel, mesh cages.
Environmental Conditions:
A photoperiod of 12 hours light from 6 a.m. to 6 p.m. Room temperature was maintained at
74-75*F. Relative humidity was maintained-at 45-47%.
Diet and Water:
ad libitum

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

A single dose of the test material was administered by gavage to animals that had been fasted
overnight.

Doses:

2000 mg compound/kg body weight

No. of animals per sex per dose:

5 males, 5 females

Control animals:

no

Details on study design:

Clinical Observations:
Animals were observed at least three times on the day of dosing (Day 0), and once each workday thereafter for the duration of the experiment (a total of 14 calendar days). Observation included, but was not limited to: examination of the hair, skin, eyes, motor activity, feces, and urine. Animals were checked for mortality on weekend days.

Body Weight Determinations:
Body weights were collected on the day of dosing (Day 0), Day 7, and Day 14 of the study.

Necrosy:
All animals were necropsied at the completion of the 14-day observation period.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

none

Clinical signs:

other: Discolored (light-brown) feces were noted from all animals on the day following dosing.

Gross pathology:

Minimal hyperkeratosis of the non-glandular gastric mucosa. for all males and three of five females.

Summary Table

DOSE (mg/kg)	NUMBER OF RATS DOSED (M,F)	NUMBER OF DEATHS <M,F)	TIME OF DEATH	WEIGHT GAIN* (M,F)
				I WEEK	2WEEKS
2000	5,5	0,0	—	5 +,5 +	5 +,5 +

*+ =Number of animals gaining weight -=Number of animals losing weight

Interpretation of results:

GHS criteria not met

Conclusions:

The test material was a gastric irritant as evidenced by hyperkeratosis of the non-glandular gastric mucosa. The acute oral LD50 for this test material was greater than 2000 mg/kg for male and female rats.

Executive summary:

An acute oral toxicity study was conducted in male and female rats administered a single limit dose of 2000 mg/kg of the test material by gavage. Discolored (light-brown) feces were noted from all animals on the day following dosing. No other abnormal clinical signs were observed during the 14-day observation period. No mortality was observed, and all animals

gained weight normally. Treatment-related changes observed at necropsy were limited to minimal hyperkeratosis of the non-glandular gastric mucosa for all males and three of five females. No other treatment-related changes or signs of organ toxicity were noted at necropsy. In the absence of significant gross organ lesions, other than the obvious signs of

gastric irritation, no tissue was collected for histological examination.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The reported study is Guideline and GLP compliant.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1943

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

Determination of the minimum lethal concentration after repeated inhalation exposure

GLP compliance:

not specified

Test type:

other: minimum lethal concentration

Limit test:

no

Specific details on test material used for the study:

Purity: 97%

Species:

rabbit

Strain:

not specified

Sex:

not specified

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

exposure chamber:
higher concentrations: 223 l metal cage
long-term inhalation at lower concentrations: battery of nine insulated plywood cages, capacity 600 l.
temperature: 23.9 ± 1.7 °C
humidity: <45%
air flow rate: 350 to 800 liters/minute
vapour generator: Bosch fuel injection pump

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

6 h

Remarks on duration:

6 hours per day

Concentrations:

0.948, 1.46,4.57 mg/l: 300 hours
11.35 mg/l: 90 hours
21.90 mg/l: 120 hours
28.75, 39.55 mg/l: 60 hours
59.9 mg/L: 1 1/5 hours

No. of animals per sex per dose:

4

Control animals:

yes

Key result

Sex:

not specified

Dose descriptor:

LC100

Effect level:

59.9 mg/L air

Based on:

test mat.

Exp. duration:

70 min

Key result

Sex:

not specified

Dose descriptor:

other: mortality

Effect level:

28.75 - < 39.55 mg/L air

Based on:

test mat.

Exp. duration:

6 h

Key result

Sex:

not specified

Dose descriptor:

other: minimum narcotic concentration

Effect level:

21.9 mg/L air

Based on:

test mat.

Exp. duration:

6 h

Mortality:

0.948 - 21.90 mg/L: none
28.75 and 39.55 mg/L: mortality in 1/4 and 4/4 animals, respectively, after 2 weeks of exposure.
59.9 mg/L: mortality in 4/4 within 70 min after exposure initiation

Clinical signs:

other: 0.948 - 11.35 mg/L: no effects 21.90 mg/L: slight lethargy. 28.75 mg/L: lethargy and impaired coordination of legs 39.55 mg/L: convulsions, light narcosis, laboured breathing, salivation, conjunctival congestion 59.55 mg/L: severe convulsions, rapid narco

Body weight:

Animals exposed to non-lethal concentrations gained weight. Mean group body weight gains were:
0.948 mg/L: 752 g (after 10 weeks)
4.57 mg/L: 956g (after 10 weeks)
11.35 mg/L: 328 g (after 3 weeks)
21.90 mg/L: 201 g (after 4 weeks)

Animals exposed to lethal concentrations lost weight. Mean group body weight gains were:
28.75 mg/L: -39 g (after 2 weeks)
39.55 mg/L: -390 g (after 2 weeks)

Gross pathology:

Histopathology: After a 3-week exposure to 11.35 mg/L barely demonstrable evidence of cellular liver and kidney injury was reported.
Potential target organs: CNS at high concentrations

Interpretation of results:

other: STOT-SE 3 H336 May cause drowsiness and dizziness

Conclusions:

In this rabbit study, all the animals died at 59.9 mg/L within 70 min after exposure initiation. LC50 was considered as between 39.6 and 59.9 mg/L. Signs of toxicity at 59.9 mg/L (70 min exposure) included severe convulsions, rapid narcosis, labored breathing, salivation, and conjunctival congestion.

Executive summary:

In this rabbit study, all the animals died at 59.9 mg/L within 70 min after exposure initiation. LC50 was considered as between 39.6 and 59.9 mg/L. Signs of toxicity at 59.9 mg/L (70 min exposure) included severe convulsions, rapid narcosis, labored breathing, salivation, and conjunctival congestion.

In this study, mortality after single and repeated exposure occurred only at high to very high concentrations of methylcyclohexane, which are above the currently valid LC50 ranges used for classification. Therefore, the study results do not fulfil the classification criteria for acute toxicity by inhalation. Based on the narcotic effects consistently observed at high concentrations in this and further studies (Weight of Evidence), methylcyclohexane fulfils the classification criteria for Specific target organ toxicity-single exposure (STOT-SE) Category 3 (narcotic effects).

Reference 2

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2005

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

abstract

Qualifier:

no guideline followed

Principles of method if other than guideline:

Acute inhalation toxicity study in mice

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Species:

mouse

Strain:

not specified

Sex:

not specified

Route of administration:

inhalation: vapour

Type of inhalation exposure:

not specified

Vehicle:

not specified

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

2 h

Control animals:

not specified

Sex:

not specified

Dose descriptor:

LC50

Effect level:

10 172 ppm

Based on:

test mat.

Exp. duration:

2 h

Sex:

not specified

Dose descriptor:

LC50

Effect level:

41.5 mg/L air

Based on:

test mat.

Exp. duration:

2 h

Interpretation of results:

GHS criteria not met

Conclusions:

In mice, a 2-hour LC50 of 41,500 mg/m3 (ca. 10,000 ppm) is reported. No detailed study description is given.

Executive summary:

In mice, a 2-hour LC50 of 41,500 mg/m3 (ca. 10,000 ppm) is reported. No detailed study description is given.

Reference 3

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2005

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: only short abstract

Justification for type of information:

Read across justification:
For justification of read across rationale see SIDS INITIAL ASSESSMENT PROFILE: Methyl/Ethylcyclohexane Category: available at:
webnet.oecd.org/HPV/UI/handler.axd?id=05fc63c8-e637-45aa-b3ff-6c19545e6c76
Citation from OECD SIDS:
"Category rationale (citation):
The methyl-ethylcyclohexane category consists of two chemicals which are methylcyclohexane and ethylcyclohexane. Both of the chemicals have a cyclohexane-ring as a basic molecular structure, and either a methyl functional group (-CH3) or an ethyl functional group (-CH2-CH3) is directly connected to this ring. Both chemicals are liquid at standard temperature and pressure. Based on the close similarity of molecular structures, all physical-chemical properties are similar.
There are a number of unifying considerations, which justify the inclusion of these two chemicals within the same category. These include:
1. Similarity of molecular structure and functional group:
These chemicals have a similar structure which is a direct connection of either methyl functional group (-CH3) or an ethyl functional group (-CH2-CH3) to the cyclohexane ring.
2. Similarity of physical-chemical properties:
All physical-chemical properties, especially water solubility, vapour pressure and log Kow are similar.
3. Similarity in health effects:
Toxicokinetic properties are similar.
Target organs of repeated dose toxicity are the liver and kidney for both chemicals.
Both chemicals show negative results of genotoxicity.
4. Similarity of environmental fate and distribution:
Both chemicals show the same or similar tendency in their environmental distribution, and biodegradation, which leads to the same behavior for these chemicals in the real environment.
5. Similarity of eco-toxicity:
Aquatic toxicity to fish (acute), daphnid (acute) and algae (acute and chronic) for both chemicals are very similar.
Analogue rationale:
Skin sensitization data of cyclohexane (CAS: 110-82-7) were used for the read across approach based on the similarity of structure. Cyclohexane is a basic molecular structure of methyl and ethylcyclohexenes."

Qualifier:

no guideline followed

Principles of method if other than guideline:

Acute inhalation toxicity study in rats

GLP compliance:

no

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

not specified

Route of administration:

inhalation: vapour

Type of inhalation exposure:

not specified

Vehicle:

not specified

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

6 h

Concentrations:

82-260 mg/l

No. of animals per sex per dose:

not specified

Control animals:

not specified

Sex:

not specified

Dose descriptor:

LC100

Effect level:

>= 82 - <= 260 mg/L air

Based on:

test mat.

Remarks on result:

other: mortality occurred within 13-70 min

Sex:

not specified

Dose descriptor:

LC0

Effect level:

11 mg/L air

Exp. duration:

6 h

Mortality:

11 mg/L: no mortality occurred
82-260 mg/L: mortality occurred within 13-70 minutes

Clinical signs:

other: 11 mg/L: only minor symptoms (lethargy in 3 hours) 82-260 mg/L: anaesthesia, lethargy, ataxia, and terminal convulsion

Interpretation of results:

other: STOT-SE 3 H336 May cause drowsiness and dizziness

Conclusions:

When rats were exposed to vapour concentrations of 82,000-260,000 mg/m3 (ca. 20,000-62,000 ppm), mortality occurred within 13-70 minutes, animals showing anaesthesia, lethargy, ataxia, and terminal convulsion. Exposure to 11,000 mg/m3 (ca. 2600 ppm), for 6 hours, induced only minor symptoms (lethargy in 3 hours)

Based on the narcotic effects observed in this study at high concentration classification of methylcyclohexane according to Regulation (EC) No 1272/2008 as STOT-SE 3 (narcotic effects) is fully justified.

Reference 4

Endpoint:

acute toxicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Study period:

2005

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: only short summary

Justification for type of information:

Justification for Read Across from methycyclohexane:

The methyl-ethylcyclohexane category was category has been agreed by OECD member countries and was evaluated and justified in the OECD SIDS INITIAL ASSESSMENT PROFILE (available at: http://webnet.oecd.org/HPV/UI/handler.axd?id=05fc63c8-e637-45aa-b3ff-6c19545e6c76).
Citation from "SIDS INITIAL ASSESSMENT PROFILE-Methyl/Ethylcyclohexane Category":

"Category rationale (citation):
The methyl-ethylcyclohexane category consists of two chemicals which are methylcyclohexane and ethylcyclohexane. Both of the chemicals have a cyclohexane-ring as a basic molecular structure, and either a methyl functional group (-CH3) or an ethyl functional group (-CH2-CH3) is directly connected to this ring. Both chemicals are liquid at standard temperature and pressure. Based on the close similarity of molecular structures, all physical-chemical properties are similar.
There are a number of unifying considerations, which justify the inclusion of these two chemicals within the same category. These include:
1. Similarity of molecular structure and functional group:
These chemicals have a similar structure which is a direct connection of either methyl functional group (-CH3) or an ethyl functional group (-CH2-CH3) to the cyclohexane ring.
2. Similarity of physical-chemical properties:
All physiccal-chemical properties, especially water solubility, vapour pressure and log Kow are similar.
3. Similarity in health effects:
Toxicokinetic properties are similar.
Target organs of repeated dose toxicity are the liver and kidney for both chemicals.
Both chemicals show negative results of genotoxicity.
4. Similarity of environmental fate and distribution:
Both chemicals show the same or similar tendency in their environmental distribution, and biodegradation, which leads to the same behavior for these chemicals in the real environment.
5. Similarity of eco-toxicity:
Aquatic toxicity to fish (acute), daphnid (acute) and algae (acute and chronic) for both chemicals are very similar"

Reason / purpose for cross-reference:

read-across source

Qualifier:

no guideline followed

GLP compliance:

no

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

not specified

Route of administration:

inhalation: vapour

Type of inhalation exposure:

not specified

Vehicle:

not specified

Duration of exposure:

6 h

Sex:

not specified

Dose descriptor:

LC0

Effect level:

11 mg/L air

Based on:

test mat.

Exp. duration:

6 h

Sex:

not specified

Dose descriptor:

LC100

Effect level:

>= 82 - <= 260 mg/L air

Based on:

test mat.

Remarks on result:

other: mortality occurred within 13-70 min

Interpretation of results:

other: STOT-SE 3, H336

Conclusions:

When rats were exposed to vapour concentrations of 82,000-260,000 mg/m3 (ca. 20,000-62,000 ppm), mortality occurred within 13-70 minutes, animals showing anaesthesia, lethargy, ataxia, and terminal convulsion. Exposure to 11,000 mg/m3 (ca. 2600 ppm), for 6 hours, induced only minor symptoms (lethargy in 3 hours).

Based on the narcotic effects observed in this study at high concentration classification of methylcyclohexane according to Regulation (EC) No 1272/2008 as STOT-SE 3 (narcotic effects) is fully justified.
Since it was judged in the SIDS INITIAL ASSESSMENT PROFILE for the Methyl-Ethylcyclohexane Category that the read across from methyl- to ethylcyclohexane is plausible and can be proven by the similarity in structure and physicochemical properties, it is assumed that ethylcyclohexane will behave in a similar manner with respect to acute inhalation toxicity. Therefore ethylcyclohexane will be classified as STOT-SE 3 (narcotic effects) too.

Executive summary:

When rats were exposed to vapour concentrations of 82,000-260,000 mg/m3 (ca. 20,000-62,000 ppm), mortality occurred within 13-70 minutes, animals showing anaesthesia, lethargy, ataxia, and terminal convulsion. Exposure to 11,000 mg/m3 (ca. 2600 ppm), for 6 hours, induced only minor symptoms (lethargy in 3 hours).

Based on the narcotic effects observed in this study at high concentration classification of methylcyclohexane according to Regulation (EC) No 1272/2008 as STOT-SE 3 (narcotic effects) is fully justified.

Since it was judged in the SIDS INITIAL ASSESSMENT PROFILE for the Methyl-Ethylcyclohexane Category that the read across from methyl- to ethylcyclohexane is plausible and can be proven by the similarity in structure and physicochemical properties, it is assumed that ethylcyclohexane will behave in a similar manner with respect to acute inhalation toxicity. Therefore ethylcyclohexane will be classified as STOT-SE 3 (narcotic effects) too.

Reference 5

Endpoint:

acute toxicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

abstract

Justification for type of information:

Justification for Read Across from methycyclohexane:

The methyl-ethylcyclohexane category has been agreed by OECD member countries and was evaluated and justified in the OECD SIDS INITIAL ASSESSMENT PROFILE (available at: http://webnet.oecd.org/HPV/UI/handler.axd?id=05fc63c8-e637-45aa-b3ff-6c19545e6c76).
Citation from "SIDS INITIAL ASSESSMENT PROFILE-Methyl･Ethylcyclohexane Category":

"Category rationale(citation):
The methyl-ethylcyclohexane category consists of two chemicals which are methylcyclohexane and ethylcyclohexane. Both of the chemicals have a cyclohexane-ring as a basic molecular structure, and either a methyl functional group (-CH3) or an ethyl functional group (-CH2-CH3) is directly connected to this ring. Both chemicals are liquid at standard temperature and pressure. Based on the close similarity of molecular structures, all physical-chemical properties are similar.
There are a number of unifying considerations, which justify the inclusion of these two chemicals within the same category. These include:
1. Similarity of molecular structure and functional group:
These chemicals have a similar structure which is a direct connection of either methyl functional group (-CH3) or an ethyl functional group (-CH2-CH3) to the cyclohexane ring.
2. Similarity of physical-chemical properties:
All physiccal-chemical properties, especially water solubility, vapour pressure and log Kow are similar.
3. Similarity in health effects:
Toxicokinetic properties are similar.
Target organs of repeated dose toxicity are the liver and kidney for both chemicals.
Both chemicals show negative results of genotoxicity.
4. Similarity of environmental fate and distribution:
Both chemicals show the same or similar tendency in their environmental distribution, and biodegradation, which leads to the same behavior for these chemicals in the real environment.
5. Similarity of eco-toxicity:
Aquatic toxicity to fish (acute), daphnid (acute) and algae (acute and chronic) for both chemicals are very similar"

Reason / purpose for cross-reference:

read-across source

Qualifier:

no guideline followed

Principles of method if other than guideline:

Acute inhalation toxicity study in mice

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Species:

mouse

Strain:

not specified

Sex:

not specified

Route of administration:

inhalation: vapour

Type of inhalation exposure:

not specified

Vehicle:

not specified

Duration of exposure:

2 h

Sex:

not specified

Dose descriptor:

LC50

Effect level:

10 172 ppm

Based on:

test mat.

Exp. duration:

2 h

Sex:

not specified

Dose descriptor:

LC50

Effect level:

41.5 mg/L air

Based on:

test mat.

Exp. duration:

2 h

Interpretation of results:

GHS criteria not met

Conclusions:

In mice, a 2-hour LC50 of 41,500 mg/m3 (ca. 10,000 ppm) is reported. No detailed study description is given.
Since it was judged in the SIDS INITIAL ASSESSMENT PROFILE for the Methyl-Ethylcyclohexane Category that the read across from methyl- to ethylcyclohexane is plausible and can be proven by the similarity in structure and physicochemical properties, it is assumed that ethylcyclohexane will behave in a similar manner with respect to acute inhalation toxicity.

Executive summary:

In mice, a 2-hour LC50 of 41,500 mg/m3 (ca. 10,000 ppm) is reported. No detailed study description is given.

Since it was judged in the SIDS INITIAL ASSESSMENT PROFILE for the Methyl-Ethylcyclohexane Category that the read across from methyl- to ethylcyclohexane is plausible and can be proven by the similarity in structure and physicochemical properties, it is assumed that ethylcyclohexane will behave in a similar manner with respect to acute inhalation toxicity.

Reference 6

Endpoint:

acute toxicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Study period:

1943

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Justification for Read Across from methycyclohexane:

The methyl-ethylcyclohexane category has been agreed by OECD member countries and was evaluated and justified in the OECD SIDS INITIAL ASSESSMENT PROFILE (available at: http://webnet.oecd.org/HPV/UI/handler.axd?id=05fc63c8-e637-45aa-b3ff-6c19545e6c76).
Citation from "SIDS INITIAL ASSESSMENT PROFILE-Methyl･Ethylcyclohexane Category":

"Category rationale
The methyl-ethylcyclohexane category consists of two chemicals which are methylcyclohexane and ethylcyclohexane. Both of the chemicals have a cyclohexane-ring as a basic molecular structure, and either a methyl functional group (-CH3) or an ethyl functional group (-CH2-CH3) is directly connected to this ring. Both chemicals are liquid at standard temperature and pressure. Based on the close similarity of molecular structures, all physical-chemical properties are similar.
There are a number of unifying considerations, which justify the inclusion of these two chemicals within the same category. These include:
1. Similarity of molecular structure and functional group
These chemicals have a similar structure which is a direct connection of either methyl functional group (-CH3) or an ethyl functional group (-CH2-CH3) to the cyclohexane ring.
2. Similarity of physical-chemical properties
All physiccal-chemical properties, especially water solubility, vapour pressure and log Kow are similar.
3. Similarity in health effects
Toxicokinetic properties are similar.
Target organs of repeated dose toxicity are the liver and kidney for both chemicals.
Both chemicals show negative results of genotoxicity.
4. Similarity of environmental fate and distribution
Both chemicals show the same or similar tendency in their environmental distribution, and biodegradation, which leads to the same behavior for these chemicals in the real environment.
5. Similarity of eco-toxicity
Aquatic toxicity to fish (acute), daphnid (acute) and algae (acute and chronic) for both chemicals are very similar"

Reason / purpose for cross-reference:

read-across source

Qualifier:

no guideline followed

Principles of method if other than guideline:

Determination of the minimum lethal concentration after repeated inhalation exposure

GLP compliance:

not specified

Test type:

other: minimum lethal concentration

Limit test:

no

Key result

Sex:

not specified

Dose descriptor:

LC100

Effect level:

59.9 mg/L air

Based on:

test mat.

Exp. duration:

70 min

Key result

Sex:

not specified

Dose descriptor:

other: mortality

Effect level:

28.75 - 39.55 mg/L air

Based on:

test mat.

Exp. duration:

6 h

Key result

Sex:

not specified

Dose descriptor:

other: minimum narcotic concentration

Effect level:

21.9 mg/L air

Based on:

test mat.

Exp. duration:

6 h

Interpretation of results:

other: STOT-SE 3 H336 May cause drowsiness and dizziness

Conclusions:

In this rabbit study, all the animals died at 59.9 mg/L within 70 min after exposure initiation. LC50 was considered as between 39.6 and 59.9 mg/L. Signs of toxicity at 59.9 mg/L (70 min exposure) included severe convulsions, rapid narcosis, labored breathing, salivation, and conjunctival congestion.

Executive summary:

In this rabbit study, all the animals died at 59.9 mg/L within 70 min after exposure initiation. LC50 was considered as between 39.6 and 59.9 mg/L. Signs of toxicity at 59.9 mg/L (70 min exposure) included severe convulsions, rapid narcosis, labored breathing, salivation, and conjunctival congestion.

In this study, mortality after single and repeated exposure occurred only at high to very high concentrations of methylcyclohexane, which are above the currently valid LC50 ranges used for classification. Therefore, the study results do not fulfil the classification criteria for acute toxicity by inhalation. Based on the narcotic effects consistently observed at high concentrations in this and further studies (Weight of Evidence), methylcyclohexane fulfils the classification criteria for Specific target organ toxicity-single exposure (STOT-SE) Category 3 (narcotic effects).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

39 600 mg/m³ air

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:

1992-01-28 - 1992-04-07

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Specific details on test material used for the study:

SRLD or Lot I.D. Number: 7482-9A
Physical State and Appearance: Colorless liquid

Species:

rat

Strain:

other: CD(SD)BR VAF/PlusT

Sex:

male/female

Details on test animals or test system and environmental conditions:

Body Weight Range at Dosing (grams): Males = 230 - 254 Females =190 - 202
Housing:
All animals were individually housed in suspended, stainless-steel, mesh cages.
Environmental Conditions:
A photoperiod of 12 hours light from 6 a.m. to 6 p.m. Room temperature was maintained at
71-75*F. Relative humidity was maintained at 45-48%.
Diet and-Water:
ad libitum

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

The hair was removed from an area of the dorsal skin with an electric clipper. A single dose of the material was placed in contact with the skin using a fiber pad and an occlusive wrap to hold the test material in place for 24 hours. At the end of the exposure period, the test material was removed with running water.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 of each sex per dose group

Control animals:

no

Details on study design:

Clinical Observations:
Animals were observed during the exposure period (Day 0) and once each workday thereafter for the duration of the experiment (a total of 14 calendar days). Observation included, but was not limited to: examination of the hair, skin, eyes, motor activity, feces, and urine. Animals were checked for mortality on weekend days.

Body Weight Determinations:
Body weights were collected on the day of dosing and one and two weeks after dosing.
Necropsy:
All animals were necropsied at the completion of the 14-day observation period.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

none

Clinical signs:

other: No treatment-related abnormal clinical signs were evident at any time during the 14-day observation period.

Gross pathology:

No treatment-related changes or signs of organ toxicity were evident at necropsy. In the absence of significant gross organ lesions, no tissue was
collected for histological examination.

Summary Table

DOSE (mg/kg)	NUMBER OF RATS DOSED (M,F)	NUMBER OF DEATHS (M,F)	TIME OF DEATH	WEIGHT GAIN* (M,F)
				1WEEK	2WEEKS
2000	5,5	0,0	--------	5 +, 5+	5 +, 5+

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal LD50 for this test material was greater than 2000 mg/kg for both sexes.

Executive summary:

A limit dose of 2000 mg/kg was applied to the skin after the hair was removed with an electric clipper. An occlusive wrap was used to hold the test material against the skin for a period of 24 hours, and at the end of exposure, residual test material was washed off with running water.

No treatment-related abnormal clinical signs were evident at any time during the 14-day observation period. On the last day of the observation period, a small wound with a scab was noted on the shoulder of a single male (Rat 745). Since this animal had appeared clinically normal from the day of dosing to Day 13, this wound was not considered related to administration of the test material. No treatment-related changes or signs of organ toxicity were evident at necropsy. In the absence of significant gross organ lesions, no tissue was collected for histological examination. Based on weight gain and survival rate, there was no evidence of percutaneous absorption. The acute dermal LD50 for this test material was greater than 2000 mg/kg for both sexes.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The reported study is guideline and GLP compleant.

Justification for classification or non-classification

Acute oral toxicity:

The respective criteria are not met. Therefore ethylcyclohexane has not to be classified for acute oral toxicity.

Acute dermal toxicity:

The respective criteria are not met. Therefore ethylcyclohexane has not to be classified for acute dermal toxicity.

Acute inhalation toxicity:

Based on the narcotic effects observed in the available studies for methylcyclohexane at high concentrations classification of methylcyclohexane according to Regulation (EC) No 1272/2008 as STOT-SE 3 (narcotic effects) is fully justified.

By applying the read-across approach ethylcyclohexane will be classified as STOT-SE 3 (narcotic effects) too.