Decanoic acid, ester with 2,2-bis(hydroxymethyl)-1,3-propanediol 2-ethylhexanoate octanoate

Endpoint summary

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:

6th March 2014-24th April, 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: ORIENTBIO INC., Korea
- Females (if applicable) nulliparous and non-pregnant: unknown
- Age at study initiation: 8 to 9 weeks old
- Weight at study initiation: 181.8 to 218.4 g
- Fasting period before study: Animals were fasted overnight, approximately 16 hours prior to dosing.
- Housing:Stainless wire mesh cage, 260W×350D×210H (mm)
- Diet (e.g. ad libitum): The feed was placed in feeders and provided ad libitum.
- Water (e.g. ad libitum):Public tap water in Cheongju-si was filtered and irradiated by ultraviolet light and provided ad libitum.
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.0 to 23.5°C
- Humidity (%): 44.5 to 62.0%
- Air changes (per hr): 10 to 15 clean, fresh, filtered air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

IN-LIFE DATES: From: Day 1 To: Day 14

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): The required amount of the test substance was weighed using an electronic balance (CP323S, Sartorius, Germany) and placed in a bottle. A small amount of vehicle, corn oil, was added and mixed using a vortex mixer until dissolved. The vehicle was gradually added to yield the desired concentrations (60 and 400 mg/mL). All preparations were conducted just prior to use.
- Justification for choice of vehicle:
- Lot/batch no. (if required): MKBP7039V


MAXIMUM DOSE VOLUME APPLIED: 5ml/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The starting dose level for this study was selected at 300 mg/kg because there is no available toxicity information on the test substance.

Doses:

300mg/kg and 2000mg/kg

No. of animals per sex per dose:

3 animals per dose.

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were observed for mortality, general condition and clinical signs (time, onset, severity and recovery) at 30 minutes after dosing and at 1, 2, 4 and 6 hours after dosing on Day 0 and once daily thereafter for 14 days (Days 1 to 14). The body weights were recorded prior to dosing (Day 0), on Days 1, 3 and 7 and on the day of necropsy, Day 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:Since no gross findings were evident at the necropsy, histopathological examinations were not performed.

Statistics:

Statistical analysis was not performed.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals dosed at 300 and 2,000 mg/kg survived the duration of the study. There were no effects on the mortality.

Clinical signs:

other: No clinical abnormalities were evident in any animals dosed at 300 and 2,000 mg/kg.

Gross pathology:

No grossly visible evidence of morphologic abnormalities was evident in any animals dosed at 300 and 2,000 mg/kg.

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

Based on the result of the acute oral toxicity study in Sprague-Dawley rats, the test substance, ADEKA PROVER H-32, was classified to be Category 5 or Unclassified according to the GHS classification.

Executive summary:

The purpose of this study was to assess the potential toxicity and to classify the test substance, ADEKA PROVER H-32, under the category of GHS classification following a single oral administration to female Sprague-Dawley rats.

Three dose groups of three females per group were utilized as follows:

Groups 1 and 2 (Steps 1 and 2): 300 mg/kg of the test substance

Groups 3 and 4 (Steps 3 and 4): 2,000 mg/kg of the test substance

Step 1: 300 mg/kg was administered. Then, there was no mortality (Step 1), and a second dose of 300 mg/kg was administered (Step 2).

Step 3: There was no mortality (Steps 1 and 2), and a third dose of 2,000 mg/kg was administered. Then, there was no mortality (Step 3) and a fourth dose of 2,000 mg/kg was administered (Step 4).

All animals were monitored for clinical signs and body weight changes during the 14-day observation period. They were subjected to gross necropsy at the end of the observation period.

There were no deaths of animals dosed at 300 and 2,000 mg/kg. No acute toxic effects were evident in clinical signs, body weight data or necropsy findings in any animals dosed at 300 and 2,000 mg/kg.

Based on the result of the acute oral toxicity study in Sprague-Dawley rats, the test substance, ADEKA PROVER H-32, was classified to be Category 5 or Unclassified according to the GHS classification.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

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

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
Low-volatility test chemicals are defined as having vapor pressures <1 x 10-5 kPa (7.5 x 10-5 mmHg) for indoor uses, and <1 x 10-4 kPa (7.5 x 10-4 mmHg) for outdoor uses at 20-30º C (Whalan et al., 1998). For H-32 the Vapour pressure result is very low 6.8 x 10-13 KPa therefore confirms low volatility. IIt has been confirmed that dermal exposure is the most likely route of exposure during industrial use. Aerosol formation is unlikely as all processes occur in a closed system. H-32 acts a grease/lubricant therefore under these conditions inhalation is unlikely.

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

other justification

Justification for data waiving:

the study need not be conducted because (i) inhalation of the substance is likely and (ii) skin contact in production and/or use is not likely and (iii) the physicochemical and toxicological properties suggest no potential for a significant rate of absorption

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING

Dermal toxicity is unlikely to result in a more severe classification than the corresponding oral hazard, therefore we can read across from the acute oral GHS classification and use the same classification for acute dermal toxicity.

Currently we can confirm that

• Acute oral toxicity is not classified.
• The 14 day repeat oral dose study shows no systemic effects.
• 28 day repeat dose NOAEL 1000mg/kg/day.
• High molecular weight confirms low permeability through the skin (greater than 500 MW)
• Partition coefficient value (Log Pow >6.5) also indicates low permeability through the skin

Based on the information listed above we can confirm dermal toxicity is unlikely and endpoint is considered as non hazardous.

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The substance is not classified for Acute toxicity as the oral LD50 is greater than 2000mg.

The Acute dermal was also waived and confirmed as non hazardous due to all physicochemical properties confirming low permeability though the skin.

The acute inhalation study was also waived as vapour pressure indicates low volatilty therefore the inhalation route is an unlikely route of exposure. Inhalation has also been confirmed as unlikely route of exposure during use as all processes occur in a closed environment.