butyl 4-hydroxycyclohexanecarboxylate

Endpoint summary

Description of key information

No test for acute oral toxicity is available for 4 -hydroxycyclohexanecarboxylic acid butyl ester. However, an oral LD50 value of 3962 mg/kg bw in the rat is available for a structurally similar compound. (Q)SAR analysis revealed that the target compound as well as the source compound will result in the same metabolite after absorption.

In addition 2 further structurally very similar compounds have been tested with LD50 values of more than 3000 mg/kg bw/day.

Therefore, based on this read-across, it can be concluded that the oral LD50 value of 4 -hydroxycyclohexanecarboxylic acid butyl ester is in the range of 3962 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

key study

Study period:

1980

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:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
[Please provide information for all of the points below. Indicate if further information is included as attachment to the same record, or elsewhere in the dataset (insert links in 'Cross-reference' table)]

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The read-across approach is justified because of common functional groups (cyclohexane ring system, carboxylic acid ester function). Moreover it can be assumed, that all substances result in the same metabolite.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
[Provide here, if relevant, additional information to that included in the Test material section of the source and target records]
Data on acute oral toxicity are available for: Ethyl cyclohexane carboxylate

3. ANALOGUE APPROACH JUSTIFICATION
see attached justification under section 13

4. DATA MATRIX
see attached justification under section 13

Reason / purpose for cross-reference:

read-across source

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

no information on necropsy provided

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: FDLR strain

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Waverly, New York
- Age at study initiation: not specified
- Weight at study initiation: 40 to 60 g
- Fasting period before study: overnight
- Diet: ad libitum
- Water: ad libitum

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

not specified

Doses:

not specified

No. of animals per sex per dose:

5 (five)

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily for 14 days
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs

Statistics:

yes, but not specified

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3 962 mg/kg bw

Based on:

test mat.

95% CL:

> 3 002 - < 5 230

Mortality:

yes

Clinical signs:

not provided

Body weight:

not provided

Gross pathology:

not performed

Interpretation of results:

other: not classified

Conclusions:

No acute oral toxicity test was performed with 4-hydroxycyclohexanecarboxylic acid butyl ester. However, a structurally close homologue was investigated for acute oral toxicity in the rat and a LD50 value of 3962 mg/kg bw was established.
The oral LD50 value of 4-hydroxycyclohexanecarboxylic acid butyl ester in the rat is considered to exceed the limit dose of 2000 mg/kg bw, based on experimental data with the very similar compound.

Executive summary:

No acute oral toxicity test was performed with 4-hydroxycyclohexanecarboxylic acid butyl ester. However, a structurally close homologue was investigated for acute oral toxicity in the rat and a LD50 value of 3962 mg/kg bw was established. The oral LD50 value of 4-hydroxycyclohexanecarboxylic acid butyl esterin the rat is considered to exceed the limit dose of 2000 mg/kg bw, based on experimental data with the very similar compound.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

key study

Study period:

1980

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:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
[Please provide information for all of the points below. Indicate if further information is included as attachment to the same record, or elsewhere in the dataset (insert links in 'Cross-reference' table)]

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The read-across approach is justified because of common functional groups (cyclohexane ring system, carboxylic acid ester function). Moreover it can be assumed, that all substances result in the same metabolite.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
[Provide here, if relevant, additional information to that included in the Test material section of the source and target records]
Data on acute oral toxicity are available for: Ethyl cyclohexane carboxylate

3. ANALOGUE APPROACH JUSTIFICATION
see attached justification under section 13

4. DATA MATRIX
see attached justification under section 13

Reason / purpose for cross-reference:

read-across source

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

no information on necropsy provided

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: FDLR strain

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Waverly, New York
- Age at study initiation: not specified
- Weight at study initiation: 40 to 60 g
- Fasting period before study: overnight
- Diet: ad libitum
- Water: ad libitum

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

not specified

Doses:

not specified

No. of animals per sex per dose:

5 (five)

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily for 14 days
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs

Statistics:

yes, but not specified

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3 881 mg/kg bw

Based on:

test mat.

95% CL:

> 3 261 - < 4 618

Mortality:

yes

Clinical signs:

not provided

Body weight:

not provided

Gross pathology:

not performed

Interpretation of results:

other: not classified

Conclusions:

No acute oral toxicity test was performed with 4-hydroxycyclohexanecarboxylic acid butyl ester. However, a structurally close homologue was investigated for acute oral toxicity in the rat and a LD50 value of 3881 mg/kg bw was established.
The oral LD50 value of 4-hydroxycyclohexanecarboxylic acid butyl ester in the rat is considered to exceed the limit dose of 2000 mg/kg bw, based on experimental data with the very similar compound.

Executive summary:

No acute oral toxicity test was performed with 4-hydroxycyclohexanecarboxylic acid butyl ester. However, a structurally close homologue was investigated for acute oral toxicity in the rat and a LD50 value of 3881 mg/kg bw was established. The oral LD50 value of 4-hydroxycyclohexanecarboxylic acid butyl ester in the rat is considered to exceed the limit dose of 2000 mg/kg bw, based on experimental data with the very similar compound.

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

key study

Study period:

1980

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:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
[Please provide information for all of the points below. Indicate if further information is included as attachment to the same record, or elsewhere in the dataset (insert links in 'Cross-reference' table)]

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The read-across approach is justified because of common functional groups (cyclohexane ring system, carboxylic acid ester function). Moreover it can be assumed, that all substances result in the same metabolite.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
[Provide here, if relevant, additional information to that included in the Test material section of the source and target records]
Data on acute oral toxicity are available for: Ethyl cyclohexane carboxylate

3. ANALOGUE APPROACH JUSTIFICATION
see attached justification under section 13

4. DATA MATRIX
see attached justification under section 13

Reason / purpose for cross-reference:

read-across source

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

no information on necropsy provided

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: FDLR strain

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Waverly, New York
- Age at study initiation: not specified
- Weight at study initiation: 40 to 60 g
- Fasting period before study: overnight
- Diet: ad libitum
- Water: ad libitum

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

not specified

Doses:

not specified

No. of animals per sex per dose:

5 (five)

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily for 14 days
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs

Statistics:

yes, but not specified

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3 265 mg/kg bw

Based on:

test mat.

95% CL:

> 2 791 - < 3 820

Mortality:

yes

Clinical signs:

not provided

Body weight:

not provided

Gross pathology:

not performed

Interpretation of results:

other: not classified

Conclusions:

No acute oral toxicity test was performed with 4-hydroxycyclohexanecarboxylic acid butyl ester. However, a structurally close homologue was investigated for acute oral toxicity in the rat and a LD50 value of 3265 mg/kg bw was established.
The oral LD50 value of 4-hydroxycyclohexanecarboxylic acid butyl ester in the rat is considered to exceed the limit dose of 2000 mg/kg bw, based on experimental data with the very similar compound.

Executive summary:

No acute oral toxicity test was performed with 4-hydroxycyclohexanecarboxylic acid butyl ester. However, a structurally close homologue was investigated for acute oral toxicity in the rat and a LD50 value of 3265 mg/kg bw was established. The oral LD50 value of 4-hydroxycyclohexanecarboxylic acid butyl ester in the rat is considered to exceed the limit dose of 2000 mg/kg bw, based on experimental data with the very similar compound.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 962 mg/kg bw

Quality of whole database:

The study is sufficiently described and well documented. A justification for the analogue approach is provided.

Justification for classification or non-classification

Based on a read-across approach, the substance must not be classified with regard to acute oral toxicity.