Tall Oil Fatty Acids, compounds with 2-(2-aminoethoxy) ethanol

Endpoint summary

Description of key information

The acute oral toxicity of the test item was assessed in accordance with OECD Guideline 420.  The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was considered to be greater than 2000 mg/kg body weight.  As such, the test item does not meet the criteria for classification. Furthermore, the acute dermal toxicity of the test item was assessed in accordance with OECD Guideline 402.  The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was considered to be greater than 2000 mg/kg body weight.  Therefore, the test item does not meet the criteria for classification.  

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:

26 May 2015 to 13 November 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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:

ANIMALS and ANIMAL HUSBANDRY
- Female Wistar rats were supplied by Envigo RMS (UK Limited, Oxon, UK.)
- The animals were randomly allocated to cages on receipt.
- Females were nulliparous and non-pregnant.
- After an acclimatisation period of at least 5 days the animals were selected at random and given a unique number within the study by indelible ink-marking on the tail and the number was written on a cage card.
- At the start of the study the animals were 8 to 12 weeks of age.
- Body weight did not exceed ± 20 % of the body weight of the initially dosed animal.
- Animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
- With the exception of an overnight fast immediately before dosing, and for approximately 3 to 4 hours after dosing, free access to mains drinking water and food (2014C Teklad Global Rodent diet supplied by Envigo RMS (UK) Limited, Oxon, UK) was allowed throughout the study.
- Diet, drinking water and bedding were routinely analysed and were considered not to contain any contaminants that would reasonably be expected to affect purpose or integrity of the study.
- Temperature and relative humidity were set to achieve limits of 19 to 25 °C and 30 to 70 % respectively.
- Rate of air exchange was at least 15 changes per hour.
- Lighting was controlled by a time switch to give 12 hours continuous light (06:00 to 18:00) and 12 hours darkness.
- Animals were provided with environmental enrichment items considered not to contain any contaminant at a level that might affect the purpose or integrity of the study.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

TEST ITEM FORMULATION and EXPERIMENTAL PREPARATION
- The test item was used as supplied.
- Specific gravity was determined to be 0.975 and used to calculate the appropriate dose volume for the required dose level.

Doses:

- Dose level: 2000 mg/kg bw
- Dose volume: 2.06 mL/kg

No. of animals per sex per dose:

- Single female animal followed, in the absence of toxicity, by an additional group of four female animals.

Control animals:

no

Details on study design:

- All animals were dosed once by gavage using a metal cannula attached to a graduated syringe.
- The volume administered to each animal was calculated according to the fasted body weight at the time of dosing.
- Treatment of animals was sequential.
- Sufficient time was allowed between each dose level to confirm the survival of the previously dosed animals.
- Clinical observations were made 0.5, 1, 2 and 4 hours after dosing and then daily for 14 days.
- Morbidity and mortality checks were made twice daily.
- Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Animals were killed by cervical dislocation at the end of the observation period.
- All animals were subjected to gross necropsy consisting of external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded but no tissues were retained.

Statistics:

The test item was evaluated according to Annex 3 of the OECD Guidelines for Testing of Chemicals No 420 "Acute Oral Toxicity - Fixed Dose Method (adopted 17 December 2001) as shown in the flow chart in Appendix 2 (attached):
- Number of animals that died during the study (or that were killed for humane reasons).
- Determination of the nature, severity, onset and duration of toxic effects (evident toxicity refers to the toxic effects of sufficient severity that administration of the next higher dose level could result in development of severe signs of toxicity and probable mortality).
- Effects on body weights and abnormalities noted at necropsy were also identified.
- Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test item was made.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

- No animal deaths took place during the study.

Clinical signs:

- No signs of systemic toxicity were noted during the observation period (see Table 1, attached).

Body weight:

- Individual body weights and body weight changes are given in Table 2 (attached).
- All animals showed expected gains in body weight over the observation period.

Gross pathology:

- Individual necropsy findings are given in Table 3 (attached).
- No abnormalities were noted at necropsy.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral toxicity of the test item was assessed in accordance with OECD Guideline 420. The acute oral median lethal dose (LD50) of the test item in the femal Wistar strain rat was considered to be greater than 2000 mg/kg body weight. As such, the test item does not meet the criteria for classification.

Executive summary:

GUIDELINE

The study was designed to be compatible with OECD Guideline for Testing of Chemicals No 420 "Acute Oral Toxicity - Fixed Dose Method" (2001) and Method B1 bis Acute Toxicity (Oral) of Commission Regulation (EC) No 440/2008.

METHOD

Following a sighting test at a dose level of 2000 mg/kg, an additional four fasted female animals were given a single oral dose of the test item at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

RESULTS

Mortality: There were no deaths.

Clinical observations: There were no signs of systemic toxicity.

Body weight: All animals showed expected gains in body weight.

Necropsy: No abnormalities were noted at necropsy.

CONCLUSION

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was considered to be greater than 2000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

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

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

09 September 2015 to 30 September 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

ANIMALS AND ANIMAL HUSBANDRY
- Five male and five femal Wistar (RccHan: WIST) strain rats were supplied by Envigo RMS (UK) Limited, Oxon, UK.
- The animals were randomly allocated to cages on receipt.
- Female animals were nulliparous and non-pregnant.
- After an acclimatisation period of at least 5 days, animals were selected at random and given a number unique within the study by indelible ink-marking on the tail and recording of the number on a cage card.
- Animals weighed at least 200 g and were 8 to 12 weeks of age at the start of the study.
- The weight variation did not exceed ± 20 % of the mean weight for each sex.
- Animals were housed in suspended solid-floor polypropylene cages furnished with woodflakes.
- The initial two animals were housed individually throughout the study.
- The further group of eight animals (four male and four female) were housed individually during the 24 hour exposure period and in groups of four, by sex, for the remainder of the study.
- Free access to mains drinking water and food (2014C Teklad Global Rodent diet supplied by Envigo RMS (UK) Limited, Oxon, UK) was allowed throughout the study.
- The diet, drinking water and bedding were routinely analysed and were considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.
- Temperature and relative humidity were set to achieve limits of 19 to 25 °C and 30 to 70 % respectively.
- The rate of air exchange was at least fifteen changes per hour.
- Lighting was controlled by a time switch to give 12 hours continuous light (06:00 to 18:00) and 12 hours darkness.
- Animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

PROCEDURE
- On the day before treatment, the back and flanks of each animal were clipped free of hair.
- One male and one female rat were initially treated with the test item at a dose level of 2000 mg/kg.
- The calculated volume (2.06 mL/kg; specific gravity 0.975) of test item, as received, was applied as evenly as possible to an area of shorn skin (approximately 10 % of the total body surface area) using a graduated syringe.
- A piece of surgical guaze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage.
- The animals were caged individually throughout the study.
- Shortly after dosing the dressings were examined to ensure they were securely in place.
- After the 24 hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with arachis oil to remove any residual test item.
- As no mortalities were noted, a further group of animals (four males and four females) were similarly treated with test item at a dose level of 2000 mg/kg bw .
- After the 24 hour contact period, the bandages were carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with arachis oil BP to remove any residual test item.
- The fanimals were returned to group housing for the remainder of the test period.
- Animals were observed for deaths or overt signs of toxicity 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days.
- After removal of the dressings and subsequently once daily for 14 days, the test sites were examined for evidence of primary irritation and scored according to the scheme attached.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

TEST FORMULATION AND EXPERIMENTAL PREPARATION
- The test item was weighed out according to each animal's individual body weight and applied undiluted as supplied.
- The absorption of the test item was not determined.

Statistics:

- Data evaluations included the relationsip, if any, between exposure of the animal to the test item and the incidence and severity of all abnormalities including behavioural and clinical observations, gross lesions, body weight changes, mortality and other toxicological effects.
- Using the mortality data obtained, and estimate of the acture dermal median lethal dose (LD50) of the test item was made.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No animal deaths took place.

Clinical signs:

No signs of systemic toxicity were observed.

Body weight:

- Individual body weights and body weight changes are shown in Table 4 (attached).
- Animals showed expected gains in body weight over the observation period except for one female, which showed no gain in body weight during the first week with expected gain in body weight during the second week.

Gross pathology:

- Individual necropsy findings are given in Table 5 (attached).
- No abnormalities were noted at necropsy.

Other findings:

DERMAL REACTIONS
- Individual dermal reactions are shown in Tables 2 and 3 (attached).
- There were no signs of dermal irritation at the test site of the initial treated male.
- Very slight erythema, with or without very slight edema, was noted at the test sites of four males and all females. Small superficial scabs and/or crust formation were noted at the test sites of six animals. There were no signs of dermal irritation noted at the test site of the initial treated male.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal toxicity of the test item was assessed in accordance with OECD Guideline 402. The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was considered to be greater than 2000 mg/kg body weight. Therefore, the test item does not meet the criteria for classification.

Executive summary:

GUIDELINE

OECD Guidelines for the Testing of Chemicals No 402 "Acute Dermal Toxicity" (adopted 24 February 1987) and Method B3 Acute Toxicity (Dermal) of Commission Regulation (EC) No 440/2008.

METHOD

Initially, two animals (one male and one female) were given a single, 24 hour, semi-occluded dermal application of the test item to intact skin at a dose level of 2000 mg/kg bw. Based on the results of the initial test, a further group of eight animals (four males and four females) were treated similarly. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

RESULTS

Mortality: No animal deaths took place during the study.

Clinical observations: No signs of systemic toxicity were observed.

Dermal irritation: Very slight erythema, with or without very slight edema, was noted at the test sites of four males and all females. Small superficial scabs and/or crust formation were noted at the test sites of six animals. There were no signs of dermal irritation noted at the test site of the initial treated male.

Body weight: Animals showed expected gains in body weight over the observation period except for one female, which showed no gain in body weight during the first week with expected gain in body weight during the second week.

Necropsy: No abnormalities were noted at necropsy.

CONCLUSION

The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was considered to be greater than 2000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

No additional data.

Justification for classification or non-classification

No adverse effect was observed during investigation of acute toxicity via the oral or dermal routes in the Wistar rat and, based on determined vapour pressure of the substance, exposure via the inhalation route is not considered to be of significance to humans. As such, classification in accordance with the CLP Regulation is not required.