Reaction mass of pentyl ester butanoic acid and 2-methylbutyl ester butanoic acid

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Cross-reference

Reason / purpose for cross-reference:

read-across: supporting information

Reference

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

weight of evidence

Justification for type of information:

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The target substance(s) will breakdown in the body into chemical groups the same as or substantially similar to the source substances. The source substance and target substances have the same or similar molecular weights, low to moderate water solubility, low partition coefficient, and are in the physical form of a liquid. The source and target substances meet Lipinski’s rule of five, indicating that the substances are likely to be similarly orally active. The potential for acute oral toxicity is therefore likely to be the same in both source and target substances.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Both the source substances and the target substance are esters, with one source and target substance being the same substance (Pentyl butyrate) and another source substance a structural isomer (a branched instead of straight chain). Both target substances have the same molecular weight and are structural isomers (one branched and one straight-chain). The other source substance has one extra methyl group on the opposite chain.
Butanoic acid would be a common breakdown product for both target substances and two of the source substances. Pentanol will be a breakdown product of the pentyl butyrate (source and target) and 3-methyl butanol or 2-methyl butanol (isomers) will be the breakdown products of the other two source substances and the target substance respectfully.
Both the source and target substances have similar physico-chemical properties (see appended full justification). A summary of the relevant properties for oral toxicity is shown below.
• All substances are liquids at room temperature with boiling points of >180 and <200 °C
• All substances have a low to moderate solubility in water (0.05-0.18 g/L)
• All substances have similar partition coefficients (Log Pow approximately 4)
Both the source and target substances pass Lipinski’s rule of five with no violations.

3. ANALOGUE APPROACH JUSTIFICATION
Due to the similarities of the source and target substance with regards to physico-chemical properties, Lipinski’s rule of 5, and the fact that the target substance is expected to breakdown into structurally similar molecules in the body, the target substance is expected to behave in a substantially similar manner in vivo.
The target substance is therefore predicted to fail to induce acute oral toxicity in an acute oral toxicity study when conducted in the rat. By extension, the target substance is considered not to fulfil the criteria for acute oral toxicity under the Classification, Labelling, and Packaging (CLP) regulation (1272/2008).

4. DATA MATRIX
See appended full justification document.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Interpretation of results:

GHS criteria not met

Data source

Reference

Reference Type:

review article or handbook

Title:

Unnamed

Year:

1964

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

No information on the method is provided in the review article.

GLP compliance:

not specified

Remarks:

No information on GLP compliance is povided in the review article.

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Pentyl butyrate

EC Number:

208-739-2

EC Name:

Pentyl butyrate

Cas Number:

540-18-1

Molecular formula:

C9H18O2

IUPAC Name:

pentyl butyrate

Test material form:

liquid

Specific details on test material used for the study:

Liquid

Test animals

Species:

rat

Strain:

Osborne-Mendel

Remarks:

Not specified in review article.

Sex:

male/female

Details on test animals or test system and environmental conditions:

fasted for 18 hours prior to treatment. Animals had access to water and food after dosing

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Close observation for 2 weeks post dose unless no toxic signs observed, then only one week.

No. of animals per sex per dose:

5

Control animals:

not specified

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

12 210 mg/kg bw

Based on:

test mat.

95% CL:

> 10 260 - < 14 560

Clinical signs:

other: Depression rough fur, wet posterior

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Executive summary:

The LD50 in the male/female rat was determined to be 12,210 mg/kg bw