COASOL 290 PLUS

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

September 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

1. HYPOTHESIS FOR THE CATEGORY APPROACH (ENDPOINT LEVEL)
The members of the category are all alcohol esters of dicarboxylic acids. All category members are manufactured by reacting an alcohol (methanol, butanol or isobutanol) with single dicarboxylic acids, succinic, glutaric or adipic acids or mixtures of these acids. The ester bonds are effectively metabolised by the body releasing the component alcohols and acids. The difference between members involves 3 parameters: 1) the alcohol used to esterify the acids, 2) the length of the acid molecule (4C, 5C or 6C) and 3) the presence of individual esters or mixtures thereof.

2. CATEGORY APPROACH JUSTIFICATION (ENDPOINT LEVEL
The toxicity profile of the members (ecotoxicity and human health toxicity and the environmental fate) is consistent. All have low acute toxicity potential, are not sensitising, are mildly irritating to eyes and upper respiratory tract (where vapour pressure allows exposure), are not genotoxic or clastogenic (in vivo) and have minimal systemic toxicity. Data are available predominantly for the methyl esters (individual and mixture), dibutyl adipate and diisobutyl esters (mixture). Within the category, read across is used to cover the higher tier human health toxicity studies predominantly.

See attached document with the justification for the category/read-across approach.

Cross-reference

Reason / purpose for cross-reference:

read-across source

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

Principles of method if other than guideline:

not applicable

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of bis(2-methylpropyl) pentanedioate, bis(2-methylpropyl) hexanedioate, bis(2-methylpropyl) butanedioate

IUPAC Name:

Reaction mass of bis(2-methylpropyl) pentanedioate, bis(2-methylpropyl) hexanedioate, bis(2-methylpropyl) butanedioate

Details on test material:

- Name of test material (as cited in study report): COASOL
- Physical state: Liquid
- Analytical purity: 100%
- Composition of test material, percentage of components: 22.9 %(w/w) Diisobutyl succinate; 56.4% (w/w) Diisobutyl glutarate; 19.1% (w/w) Diisobutyl adipate
- Purity test date: 07/Aug/2009
- Lot/batch No.: 50046869
- Expiration date of the lot/batch: 05/August/2010
- Stability under test conditions: stable
- Storage condition of test material: room temperature in the dark

Specific details on test material used for the study:

COASOL: DBE-IB

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Ltd.
- Age at study initiation: 8 - 12 weeks
- Fasting period before study: yes
- Housing: The animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes
- Diet (e.g. ad libitum): yes
- Water (e.g. ad libitum): yes
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30- 70 %
- Air changes (per hr): 15 changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours light/dark cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

All animals were dosed once only by gavage using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 females. Only females were used as they are typically more sensitive, and are the preferred choice when it is unknown if there is a sex difference in toxicity

Control animals:

no

Details on study design:

1 animal dosed first, then in the absence of toxicity at the dose of 2000 mg/kg bw/day 4 additional animals were dosed with 2000 mg/kg bw/day. Clinical observations were made at 0.5, 1, 2, and 4 hours following dosing and then once daily for the remaining 14 days. Individual bodyweights were recorded at day 0 and day 7. At the end of observation period animals were euthenized by cervical dislocation and subject to gross necropsy consisting of external examination and opening of the abdominal and thoracic cavities. Any macroscopic abnormalities were noted.

Statistics:

not applicable

Results and discussion

Preliminary study:

not applicable

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

There were no deaths

Clinical signs:

other: There were no clinical signs of toxicity

Gross pathology:

No abnormalities identified at necropsy

Other findings:

none

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:

not classified

Conclusions:

There were no deaths at the limit dose of 2000 mg/kg bw. Therefore this substance does not require classification for acute oral toxicity.

Executive summary:

An acute oral toxicity study in female rats was conducted according to OECD TG 420 and in accordance with the Principles of Good Laboratory Practice (GLP). One female animal dosed first, then in the absence of toxicity at the dose of 2000 mg/kg bw/day four additional animals were dosed with 2000 mg/kg bw/day. Clinical observations were made at 0.5, 1, 2, and 4 hours following dosing and then once daily for the remaining 14 days. Individual bodyweights were recorded at day 0 and day 7. At the end of observation period animals were euthenized by cervical dislocation and subject to gross necropsy consisting of external examination and opening of the abdominal and thoracic cavities. Any macroscopic abnormalities were noted. There were no deaths and no clinical signs of toxicity, based on which the the substance does not require classification for acute oral toxicity.