Tall oil, compd. with ethanolamine

Endpoint summary

Description of key information

ACUTE TOXICITY: ORAL
- LD50 >2000 mg/kg bodyweight to female Wistar strain rats
ACUTE TOXICITY: DERMAL
- LD50 of crude tall oil >2000 mg/kg bw in male and female Sprague-Dawley rats
- LD50 of ethanolamine in the New Zealand White rabbit was 2.46 mL/kg in males and 2.83 mL/kg in females

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:

20 August 2012 to 12 September 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain: RccHan:WIST
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: The animal dosed first weighed 162 g. The bodyweight variation did not exceed ± 20 % of the initially dosed animal.
- Fasting period before study: Yes. The animals were fasted overnight prior to dosing and for approximately 3 to 4 hours post-dosing.
- 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): ad libitum.
- Water (e.g. ad libitum): ad libitum access to mains tap water.
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25 °C
- Humidity (%): 30 to 70 %
- Air changes (per hr): At least 15 changes per hour.
- Photoperiod (hrs dark / hrs light): The lighting was controlled by a time switch to give twelve hours continuous light (0600 to 1800) and twelve hours darkness.

IN-LIFE DATES: From: 20 August 2012 To: 12 September 2012

Route of administration:

oral: gavage

Vehicle:

DMSO

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Justification for choice of vehicle: The test material did not dissolve in distilled water or arachis oil BP.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 female animals per dose

Control animals:

no

Details on study design:

Following a sighting test with a single animal being treated at a dose level of 2000 mg/kg bodyweight, an additional four fasted animals were dosed at the same level.

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days. Morbidity and mortality checks were made twice daily. Individual bodyweights were recorded on day 0 (the day of dosing) and on days 7 and 14.
- Necropsy of survivors performed: Yes; all animals were subjected to gross necropsy. Animals were killed by cervical dislocation. An external examination was performed and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded.

Preliminary study:

There was no mortality in the sighting test and no clinical observations noted.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

No signs of systemic toxicity were observed.

Body weight:

All animals showed the expected gains in bodyweight over the observation period.

Gross pathology:

No abnormalities were noted at necropsy.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the acute oral LD50 was >2000 mg/kg bodyweight in female Wistar strain rats and the test material requires no classification in accordance with EU criteria.

Executive summary:

The acute oral toxicity potential of the test material to female Wistar strain rats was assessed in accordance with the standardised guidelines OECD 420 and EU Method B.1 bis under GLP conditions.

Following a sighting test in a single animal at a dose level of 2000 mg/kg, the test material was administered by gavage at the same dose level to an additional four animals. The animals were observed for 14 days.

There was no mortality and no clinical signs were observed. All animals showed the expected gains in bodyweight throughout the observation period.

Under the conditions of this study, the acute oral LD50 was >2000 mg/kg bodyweight and the test material requires no classification in accordance with EU criteria.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The key study was conducted under GLP conditions in accordance with the standardised guidelines OECD 420 and EU Method B.1 bis. It was assigned a reliability score of 1 in accordance with the criteria detailed by Klimisch (1997).

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The key study on the read across material crude tall oil was conducted under GLP conditions in accordance with the standardised guidelines OECD 402 and EU Method B.3. It was assigned a reliability score of 2 in accordance with the criteria detailed by Klimisch (1997).

The second key study on the read across substance ethanolamine was carried out in a procedure equivalent to the standardised OECD 402 guideline. It was assigned a reliability score of 2 in accordance with the criteria detailed by Klimisch (1997).

Additional information

Acute Toxicity: Oral

The acute oral toxicity potential of the test material to female Wistar strain rats was assessed in accordance with the standardised guidelines OECD 420 and EU Method B.1bis under GLP conditions.

Following a sighting test in a single animal at a dose level of 2000 mg/kg, the test material was administered by gavage at the same dose level to an additional four animals. The animals were observed for 14 days.

There was no mortality and no clinical signs were observed. All animals showed the expected gains in bodyweight throughout the observation period.

Under the conditions of this study, the acute oral LD50 was >2000 mg/kg bodyweight and the test material requires no classification in accordance with EU criteria.

 

Acute Toxicity: Inhalation

In accordance with the Column 2 adaptation of Annex VIII of Regulation (EC) 1907/2006 (REACH), it is considered justified to omit the acute toxicity by the inhalation route study (required under point 8.5.2) as testing by this route is inappropriate. Exposure via the inhalation route is not relevant due to the substance being an immobile paste with a low vapour pressure; therefore the acute oral and acute dermal studies are deemed more appropriate to address acute toxicity exposure.

 

Acute Toxicity: Dermal

This endpoint was addressed using a read across approach to structural analogues of the registered substance. Two key studies are provided, one on tall oil and one on ethanolamine. In this respect it is considered that the data submitted provides an adequate reflection of the test material.

 

The potential of the read across material crude tall oil to cause acute toxic effects when administered by the dermal route was investigated in accordance with the standardised guidelines OECD 402 and EU Method B.3 under GLP conditions.

The test material was administered once dermally on the dorsal thoracal region of 5 male and 5 female Sprague Dawley rats at a limit dose of 2000 mg/kg bw.

A cellulose patch with the individually weighed amount of the test material on the surface was applied to the test site and held in place by fixing marginally with non irritating tape. This was covered by a semi-occlusive dressing and left in place for 24 hours.

There was no mortality and no local or systemic effects related to administration of the test material. All animals appeared normal at necropsy.

Under the conditions of this study the LD50 was found to be >2000 mg/kg bw in male and female rats and therefore requires no classification in accordance with EU criteria.

 

In the second key study, the acute dermal toxicity of the read across substance ethanolamine was investigated in a procedure equivalent to the standardised OECD 402 guideline.

New Zealand White rabbits were subjected to 24 hours of occlusive contact with the test material (1.0, 2.0, or 4.0 mL/kg, 5 animals per sex per dose). After the contact period, excess fluid was removed to diminish ingestion. Observations for toxicity and skin reactions were made at one hour, 7 days, and 14 days after the contact period. Animal weights were recorded at 0 days (before dose), 7 days and 14 days (just prior to termination). LD50 values and the estimated LD50 slopes were calculated by the moving average method (Thompson, 1947; Weil, 1983) and are based on a 14 day observation period. At death or termination, each animal was subjected to a gross pathologic evaluation.

Nine of the animals in the 4.0 mL/kg dosing group died; 2 animals in the 2.0 mL/kg dosing group died and no mortality was seen on the 1.0 mL/kg dosing group.

Clinical observations included erythema, edema, necrosis, ecchymosis, desquamation, ulceration, alopecia, scabs, sluggishness, abdominal distension and emaciation.

The LD50 value for males was 2.46 mL/kg (2504 mg/kg) with a 95 % confidence level of 1.79 to 3.39 mL/kg (1822 to 3451 mg/kg). The LD50 value for females was 2.83 mL/kg (2881 mg/kg) with a 95 % confidence level of 1.61 to 4.98 mL/kg (1639 to 5070 mg/kg). Under the conditions of this study the test material requires no classification in accordance with EU criteria.

Justification for selection of acute toxicity – oral endpoint
Only one study available.

Justification for selection of acute toxicity – inhalation endpoint
A data waiver has been submitted to address this endpoint.

Justification for selection of acute toxicity – dermal endpoint
This endpoint was addressed using a read across approach to structural analogues of the registered substance and so no single study was selected. Two key studies are provided, one on tall oil and one on ethanolamine. In this respect it is considered that the data submitted provides an adequate reflection of the test material.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation 1272/2008, the test material does not require classification for acute toxicity.