Resin acids and Rosin acids, esters with glycerol and diethylene glycol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2021

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2021

Report date:

2021

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

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:

Resin acids and Rosin acids, esters with glycerol and diethylene glycol

EC Number:

288-327-7

EC Name:

Resin acids and Rosin acids, esters with glycerol and diethylene glycol

Cas Number:

85711-66-6

Molecular formula:

UVCB substance

IUPAC Name:

esterification product of (1R,4aR,4bR,10aR)-1,4a-dimethyl-7-(propan-2-yl)-1,2,3,4,4a,4b,5,6,10,10a-decahydrophenanthrene-1-carboxylic acid; (1R,4aR,4bS,10aR)-1,4a-dimethyl-7-(propan-2-ylidene)-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenanthrene-1-carboxylic acid; (1R,4aS,10aR)-1,4a-dimethyl-7-(propan-2-yl)-1,2,3,4,4a,5,6,9,10,10a-decahydrophenanthrene-1-carboxylic acid; (1R,4aS,10aR)-1,4a-dimethyl-7-(propan-2-yl)-1,2,3,4,4a,9,10,10a-octahydrophenanthrene-1-carboxylic acid and 2,2'-oxydiethanol and propane-1,2,3-triol

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source (i.e. manufacturer or supplier) and lot/batch number of test material: 3M, Lot K02007

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature, store protected from light, Test article is not oxygen-sensitive.
- Stability and homogeneity of the test material in the vehicle/solvent under test conditions (e.g. in the exposure medium) and during storage: no data.
- Stability in the medium, i.e. sensitivity of the test material to hydrolysis and/or photolysis: no data.
- Solubility and stability of the test material in the solvent/vehicle and the exposure medium: no data.
- Reactivity of the test material with the incubation material used (e.g. plastic ware): no data.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing (e.g. warming, grinding): The test article was formulated to 25% (w/v) with distilled water and mixed via vortex.
- Preliminary purification step (if any): no data.
- Final concentration of a dissolved solid, stock liquid or gel: 25% (w/v)
- Final preparation of a solid (e.g. stock crystals ground to fine powder using a mortar and pestle): no data.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River
- Females (if applicable) nulliparous and non-pregnant:yes
- Rationale for use of males (if applicable) : n/a
- Age at study initiation: Animals will be 8 to 12 weeks at the commencement of each dosing.
- Weight at study initiation: The initial weight of each animal will not exceed 20% of the mean of the previously dosed animals of the same sex.
- Fasting period before study: Fresh, Certified Rodent Lab Diet® No. 5002 (or similar) will be available ad libitum during acclimation and the study except for 16 to 20 hours prior to test article administration
- Housing: Animals will be group-housed by dose group in suspended wire-bottom cages that conform to the size recommendations in the Guide for the Care and Use of Laboratory
Animals (National Research Council).
- Historical data: Historical control data is stored by the contract laboratory for statistical comparisons.
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 5, 50, 300, 2000 or 5000 mg/kg body weight.
- Amount of vehicle (if gavage): no data
- Justification for choice of vehicle:no data
- Lot/batch no. (if required): no data
- Purity: no data.

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg

DOSAGE PREPARATION (if unusual):

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:Initially, a single dose was administered orally by syringe and dosing needle at a dose level of 2000 mg/kg
to three female rats. Since two out of three rats died, an additional six female rats were dosed at a level of 300 mg/kg.

Doses:

300 and 2,000 mg/kg bw

No. of animals per sex per dose:

3 animals were dosed at 2,000 mg/kg bw and 6 at 300 mg/kg bw.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals will be observed at least at the following intervals: 15 (± 5) minutes, one, two, and four hours post-dosing, and once daily thereafter for 14 days. All animals will be observed twice daily for mortality on Day 1 through Day 14.
- Necropsy of survivors performed: yes
- Clinical signs including body weight : yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:Observations will include, but not be limited to, evaluation of skin and fur, eyes and
mucous membranes, respiratory and circulatory effects, autonomic effects such as
salivation, central nervous system effects including tremors and convulsions, changes
in the level of activity, gait and posture, reactivity to handling or sensory stimuli, altered
strength, and stereotypies or bizarre behavior (e.g., self-mutilation, walking
backwards).

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Dose Level: 2000 mg/kg- two female rats died by dat 4 and one female rat survived following a single 2000 mg/kg oral dose.
Dose Level: 300 mg/kg- all six female rats survived following a single 300 mg/kg oral dose.

Clinical signs:

other: Chromorhinorrhea, wetness and red staining of the anogenital and nose/mouth area, piloerection, and hunched posture were observed.

Gross pathology:

In 2000 mg/kg group- the gross necropsy revealed red staining of the nose/mouth area, red areas on the adrenal glands, and abnormalities of the gastrointestinal tract.
In 300 mg/kg group- the gross necropsy revealed no observable abnormalities.

Other findings:

None.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Based on the results of the study, the oral LD50 of the rosin acid derivative was greater than 300 mg/kg but less than 2,000 mg/kg.

Executive summary:

The acute oral toxicity of Rosin Acid Derivative (Lot:K02007) was tested in Sprague Dawley rats. The study was conducted according to GLP. The test method was conducted based on the OECD Guideline no. 423. The test article was formulated to 25% (w/v) with distilled water and mixed via vortex. The food for each rat was removed from each cage 16-20 hours prior to dosing and each animal was then weighed. The test article was administered orally once on study Day 1 by a syringe and a dosing needle on an mg/kg basis. Animals were observed at least at the following intervals: 15 (± 5) minutes, one, two-, and four-hours post-dosing, and once daily thereafter for 14 days. All animals will be observed twice daily for mortality on Day 1 through Day 14. Surviving animals were euthanized using CO2 and were examined for gross pathology following study termination. Three female rats were initially dosed with 2000 mg/kg test material where two female rats died by Day 4 and one female rat survived the 14-day recovery period. In this group, prior to death, abnormal physical signs of toxicity including chromorhinorrhea, wetness and red staining of the anogenital and nose/mouth area, piloerection, and hunched posture were observed. Terminal body weight loss was observed following the unscheduled deaths. The gross necropsy revealed red staining of the nose/mouth area, red areas on the adrenal glands, and abnormalities of the gastrointestinal tract. The animal that survived the single 2000 mg/kg oral dose gained weight from pretest to study termination and the gross necropsy revealed red areas on the adrenal glands. Subsequently, six female rats were dosed with 300 mg/kg test material. All six female rats survived through the 14-day recovery period. In this group, all six animals gained weight from pretest to study termination. Body weight loss was observed among two animals from Day 7 to Day 14. The gross necropsy revealed no observable abnormalities. Based on the results of the study, the oral LD50 of the rosin acid derivative was greater than 300 mg/kg but less than 2,000 mg/kg.