Reaction mass of diisobutyl adipate and diisobutyl glutarate and diisobutyl succinate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

key study

Study period:

January 09 to March 26, 1987

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.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of dimethyl esters of adipic, glutaric and succinic acids

IUPAC Name:

Reaction mass of dimethyl esters of adipic, glutaric and succinic acids

Details on test material:

- Name of test material (as cited in study report): RP/DE
- Physical state: colorless liquid

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, F-76410 Saint Aubin les Elbeuf, France;
- Weight at study initiation: males: 266 ± 2 g, females: 247 ±10 g;
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6 days;


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 60 ± 20
- Photoperiod (hrs dark / hrs light): 12/12;

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 5 x 7 cm²; shaved backs and flanks
- % coverage: < 10%;
- Type of wrap if used: gauze


REMOVAL OF TEST SUBSTANCE
- Washing (if done): not specified;
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): not specified;
- Concentration (if solution): 2000 mg/kg bw;

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw;

No. of animals per sex per dose:

5 males;
5 females;

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations: at least once daily; weighting: at days 1 (pre-administration), 5, 8, and 15
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occured.

Clinical signs:

other: No clinical signs of toxicity were detected.

Gross pathology:

No signs of gross pathology have been detected

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

Under the conditions of the current study, the test article DBE showed no signs of toxicity in female and male rats over a period of 14 days when applied dermally once at 2000 mg/kg bw. The LD50 can therefore be concluded to be greater than 2000 mg/kg bw. Based on this Result DBE is not classified according to Annex VI of the Directive 67/548/CEE and according to EU Regulation 1272/2008 (CLP).

Executive summary:

DBE has been tested in an acute dermal toxicity study using Crj: CD(SD) rats, according to OECD guideline n° 402 and EU guideline n° B.3 in compliance with Good Laboratory Practice. The test item was applied once under semiocclusive conditions to the shaved backs and flanks of the animals at a dose level of 2000 mg/kg for 24 h (5 males + 5 females per dose, 5 x 7 cm²). Clinical signs, mortality and body weight gain were checked for a period of up to 14 days after the single administration of DBE. All animals were subjected to necropsy. No mortality was recorded in both groups during the study. Body weight gain of the treated animals was not affected by treatment. At necropsy, no abnormalities were observed in any animal. As the LD50 is higher than 2000 mg/kg, DBE is not classified according to Annex VI of the Directive 67/548/CEE and according to EU Regulation 1272/2008 (CLP).