2-ethylhexyl 3,5,5-trimethylhexanoate

Endpoint summary

Description of key information

LD50 (oral, rat) = 5000 mg/kg

LD50 (dermal): >2000 mg/kg (assumed)
LC50 (inhalative): not tested

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2016-11-29 to -2017-02-22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: ORIENTBIO INC., Republic of Korea
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 weeks old
- Weight at study initiation: 184.1-201.0 g
- Fasting period before study: Not given
- Housing: Stainless wire mesh cage, 260W×350D×210H (mm), one animal/cage (during the study)
- Diet (e.g. ad libitum): Pelleted rodent chow, (Teklad Certified Irradiated Global 18% Protein Rodent Diet 2918C)
- Water (e.g. ad libitum): Public tap water in Cheongju-si was filtered and irradiated by ultraviolet light and provided ad libitum.
- Acclimation period: Yes. For 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Measurement value: 21.0-24.8°C; permissible range: 19.0-25.0°C
- Humidity (%): Measurement value: 47.9-62.9%; permissible range: 30.0-70.0%
- Air changes (per hr): 10-15 clean, fresh, filtered air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

IN-LIFE DATES: From 2016-12-9 To: 2017-02-22

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 2000 mg/kg
- Amount of vehicle (if gavage): 5mL/kg bodyweight
- Lot/batch no. (if required): 10700018
- Purity: 99.8

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Due to the low expected toxicity of the test substance, 2,000 mg/kg was selected as the starting dose for this study based on the information supplied by the sponsor.

Doses:

2000 mg/kg

No. of animals per sex per dose:

6 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 30 min, 1, 2, 4, 6 hours after dosing
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology

Statistics:

Statistical analysis was not performed. Mean scores and values were determined.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

>= 5 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths of animals at 2,000 mg/kg throughout the study.

Clinical signs:

other: No abnormalities of clinical signs were observed in any animal at 2,000 mg/kg throughout the study.

Gross pathology:

No grossly visible findings were observed in any animal at 2,000 mg/kg.

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Based on the result of the acute oral toxicity study in Sprague-Dawley rats (LD 50 cut off >=5000 mg/kg b.w., the test substance was considered Unclassified according to the GHS classification.

Executive summary:

The purpose of this study was to assess the potential toxicity of the test substance following a single oral dose administration to female Sprague-Dawley rats and to classify the test substance under the category of GHS classification.

Two dose groups of three females were utilized as follows:

Groups 1 and 2 (Steps 1 and 2): 2,000 mg/kg of the test substance

Steps 1-2: A dose of 2,000 mg/kg was administered to group 1 (Step 1) and then, as there was no mortality, a second dose of 2,000 mg/kg was administered to group 2 (Step 2).

All animals were monitored for clinical signs and body weight changes during the 14-day observation period, after which time they were subjected to a gross necropsy.

There were no mortalities in any animals following administration of 2,000 mg/kg and no test substance-related effects on clinical signs, body weight data or necropsy findings.

Based on the result of the acute oral toxicity study in Sprague-Dawley rats, the test substance, was not classified according to the GHS classification.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

Key study was of good quality, hence was assigned 1 (reliable without restriction) and was carried out under GLP.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

other:

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

In studies with a structurally similar analog, dermal penetration was 7-8%. This analogue substance is a slightly smaller molecule (molecular weight 256.4) which would be predicted to have higher dermal penetration potential than the larger test substance. Assuming a maximum dermal penetration factor for the test substance of 8%, the systemic exposure after dermal application of 1000 mg/kg/day (limit dose) would be 80 mg/kg/day. This projected exposure is near the NOEL from the repeat-dose oral study and less than the LOEL observed in that study. Thus, it is unlikely a dermal study with Dragoxat 89 would yield effects useful for assessing risk by this route. (For futher discussion, please refer to the attached document (Justification for Classification (STOT RE: oral) in IUCLID section 13 (STOT RE justification).

The low vapor pressure of Dragoxat 89, 0.094 Pa at 25 C precludes significant exposure to Dragoxat 89 vapor by inhalation. In addition, this material is not intended for use in spray applications. Thus, exposure to humans by inhalation is unlikely.

Human information: No human information is available.

Justification for selection of acute toxicity – oral endpoint
Valid guideline study performed as limit test with 2000 mg/kg bw dose without any mortality.

Justification for selection of acute toxicity – inhalative endpoint
As no adverse effects are observed this study is waived as described above

Justification for selection of acute toxicity – dermal endpoint
As no adverse effects are observed this study is waived as described above

Justification for classification or non-classification

Based on the findings and rationale the substance is not subject to classification for acute oral toxicity according to CLP (Regulation EC No 1272/2008). Data on acute inhalative and dermal toxicity are not available and not required and the substance is not classified for acute inhalative and dermal toxicity.

Given the results from the acute oral toxicity study and the dose range finding study (14 days exposure), despite slight mortality in the OECD 422 study, no classification appears necessary for specific target organ toxicity, single exposure according to CLP (Regulation EC No 1272/2008).