Fatty acids, C16-18 (even numbered), reaction products with tetraethylenepentamine, acetates (salts)

Endpoint summary

Description of key information

Acute oral toxicity: LD50 > 2000 mg/kg bw, OECD Guideline 423, GLP 
Acute dermal toxicity: LD50 > 2000 mg/kg bw, OECD guideline 402, GLP
Acute inhalation toxicity: not necessary due to exposure considerations

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-JAN-2005 - 18-FEB-2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(29 April 2004)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(17 December 2001)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

- Name of test material: Fatty acids, C16-18, reaction products with tetraethylenepentamine, acetates (salts)

Species:

rat

Strain:

other: HanBrl: Wist (SPF)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd, Laboratory Animal Services, CH-4414 Fullinsdorf / Switzerland
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 12 wk
- Fasting period before study: yes; approximately 17 to 18 hours
- Housing: groups of three in Makrolon type-4 cages
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 92/04 (Provimi Kliba AG, CH-4303 Kaiseraugst/Switzerland), ad libitum
- Water (e.g. ad libitum): Community tap water from Fullinsdorf, ad libitum
- Acclimation period: 7 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3°C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

(deionised, purified)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.2 g/mL

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg body weight

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality / Viability: Daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15.
Body weights: On test days 1 (prior to administration), 8 and 15.
Clinical signs: Daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1. Once daily during days 2-15.
- Necropsy of survivors performed: yes

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr.

Mortality:

No deaths occurred during the study.

Clinical signs:

other: No clinical signs were observed during the course of the study.

Body weight:

other body weight observations

Remarks:

The body weight of the animals was within the range commonly recorded for this strain and age.

Gross pathology:

No macroscopic findings were recorded at necropsy.

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 of 16-18FA-TEPA-compound in female rats was >2000 mg/kg bw.

Executive summary:

In an acute oral toxicity study according to OECD guideline 423 (17 December 2001) and EU method B.1 tris (29 April 2004), two groups, each of three female HanBrl: WIST (SPF) rats, were treated with 16-18FA-TEPA-compound by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was diluted in vehicle (purified water) at a concentration of 0.2 g/mL and administered at a volume dosage of 10 mL/kg.
The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs at approximately 30 minutes, 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Mortality/viability was recorded at approximately 30 minutes, 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15.
Body weights were recorded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.
All animals survived until the end of the study period.
No clinical signs were observed during the course of the study.
The body weight of the animals was within the range commonly recorded for this strain and age.
No macroscopic findings were recorded at necropsy.

Oral LD50 Females > 2000 mg/kg bw

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

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:

05-JAN-2005 - 26-JAN-2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(31 July 1992)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

(24 February 1987)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

- Name of test material: Fatty acids, C16-18, reaction products with tetraethylenepentamine, acetates (salts)

Species:

rat

Strain:

other: HanBrl: WIST (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd, Laboratory Animal Services, CH-4414 Fillinsdorf / Switzerland
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: Males: 8 weeks, Females: 12 weeks
- Housing: During acclimatization in groups of five per sex in Makrolon type-4 cages with standard softwood bedding. Individually in Makrolon type-3 cages with standard softwood bedding during treatment and observation.
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 42/04 (Provimi Kliba AG, CH-4303 Kaiseraugst/ Switzerland) ad /ibitum.
- Water (e.g. ad libitum): Community tap water from Fillinsdorf ad libitum.
- Acclimation period: 7 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 + 3°C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

water

Remarks:

(deionised, purified)

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Mortality / Viability: Daily during the acclimatization period, at approximately 1, 2, 3 and 5hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15.
- Body weights: On test days 1 (prior to administration), 8 and 15.
- Clinical signs: Daily during acclimatization and at approximately 1, 2, 3 and 5 hours after administration on test day 1. Once daily during days 2-15. All abnormalities were recorded.
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr.

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal LD50 in rats (male/female) of C16-18FA-TEPA-compound was > 2000 mg/kg bw.

Executive summary:

In an acute dermal toxicity study according to OECD guideline 402 (24 February 1987) and EU method B.3 (31 July 1992), groups of young adult HanBrl: WIST rats (5/sex) were dermally exposed to C16 -18FA-TEPA-compound in purified water for 24 hours to approx. 10% body surface area at a limit dose of 2000 mg/kg bw. Animals then were observed for 14 days. The test substance was applied as solution of 0.33 g/mL.

No deaths occurred during the study. The only clinical signs noted were slight general erythema in five males and four females on day 2 which persisted up to day 3, 5, 7 and 8 in the male and up to day 4, 5 and 8 in the female animals and slight swelling on day 2 in one female. The body weight was within the range commonly recorded for this strain and age. No macroscopic abnormalities were observed at necropsy.

 

Dermal LD50 male/female > 2000 mg/kg bw

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Acute toxicity studies with 1618FA-TEPA-compound are available for the oral and dermal route as well as for the source substance used for read-across (partially unsaturated IQAC, DMS quaternised) for higher tier endpoints.

 

Acute oral toxicity

In an acute oral toxicity study according to OECD guideline 423 (17 December 2001) and EU method B.1 tris (29 April 2004), 6 fasted,12 weeks old female HanBrl: Wist rats were given a single oral dose of 1618FA-TEPA-compound in purified water at alimit dose of 2000 mg/kg bw and observed for 14 days.The test substance was applied as solution of 0.2 g/mL.

No deaths occurred during the study. No clinical signs were observed. The body weight was within the range commonly recorded for this strain and age. No macroscopic findings were recorded at necropsy. Oral LD50 Females > 2000 mg/kg bw

 

The source substance was of similarly low toxicity: In an acute oral toxicity study test performed according to the OECD Guideline 423, 2001, 6 female 11 weeks old HanRcc:WIST (SPF) rats were given a single oral dose of partially unsaturated IQAC,DMS quaternised (100 % a.i.) in corn oil at doses of 2000 mg/kg bw and observed for 14 days.

All animals survived until the end of the study period. No clinical signs were observed during the course of the study. The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were recorded at necropsy.

Oral LD50 females > 2000 mg/kg bw

 

Acute inhalation toxicity

Given that inhalation is not a relevant route of exposure, testing by the inhalation route is not necessary according to REACH Regulation Annex VIII 8.5.2 Column 2. Inhalation is not a relevant route of exposure to C1618FA-TEPA-compound. This applies to both workers and the general population and is due to the physicochemical properties of the substance and the nature of the products where it is used. C1618FA-TEPA-compound is solid at room temperature, and the substance is manufactured and marketed as flakes. Generation of inhalable particles such as dust or aerosols is not to be expected.

Vaporisation needs not to be considered due to the substance’s low vapour pressure (<0.001 Pa at 20°C).

The generation of aerosols is excluded by technical means or product design. The substance is not used in spray applications. The most likely route of human exposure for workers and consumers is the dermal route. Results of laboratory animal studies show a low acute toxicity after oral and dermal exposure. Therefore the acute intrinsic toxic activity of C1618FA-TEPA-compound is considered to be low. The occurrence of a systemic toxicity relevant to humans after inhalation is unlikely and therefore the conduct of an acute inhalation toxicity study is unjustified.

 

Acute dermal toxicity

In an acute dermal toxicity study according to OECD guideline 402 (24 February 1987) and EU method B.3 (31 July 1992), groups of young adult HanBrl: WIST rats (5/sex) were dermally exposed to C16 -18FA-TEPA-compound in purified water for 24 hours to approx. 10% body surface area at a limit dose of 2000 mg/kg bw. Animals then were observed for 14 days. The test substance was applied as solution of 0.33 g/mL.

No deaths occurred during the study. The only clinical signs noted were slight general erythema in five males and four females on day 2 which persisted up to day 3, 5, 7 and 8 in the male and up to day 4, 5 and 8 in the female animals and slight swelling on day 2 in one female. The body weight was within the range commonly recorded for this strain and age. No macroscopic abnormalities were observed at necropsy.

Dermal LD50 male/female > 2000 mg/kg bw

 

The source substance was of similarly low toxicity: In an acute dermal toxicity study according to OECD guideline 402, 1987 and EU method B.3, 1992, 5 male and 5 female young adult HanRcc: WIST(SPF) rats were dermally exposed to the partially unsaturated IQAC, DMS quaternised suspended in corn oil for 24 hours under a semi-occlusive dressing to approx. 10 % of body surface area at doses of 2000 or 200 mg/kg bw. Low dose group animals then were observed for 14 days. The high dose animals were euthanized due to severe local effects after ten days. No symptoms of systemic toxicity were observed. The local skin reactions affected the study and prevented the full assessment of the LD50. However, even though the 14 day observation period could not be completed the onset of systemic toxicity should have been apparent on day 10.

No mortality occurred in this test. No clinical signs or gross pathological findings were observed. No weight gain or slight (< 1 %) weight loss was observed in three females of the high dose group (2000 mg/kg bw) and a slight (0.7 % during the first week) but reversible weight loss in one female of the low dose group (200 mg/kg bw). The minor body weight loss or absence of body weight gain in a few number of females is generally well associated to the female animals which are more sensitive or body weight-affected than the males after dermal exposure. Therefore, the affected body weight suggested a relationship to the type of application and sex of animals rather than any local (the local findings were comparable in both sexes) or systemic toxicity of the test item.

Dermal LD50 males > 2000 mg/kg bw

Dermal LD50 females > 2000 mg/kg bw

Dermal LD50 combined > 2000 mg/kg bw

 

Based on the available information, the acute toxicity of C16 -18FA-TEPA-compound is low. There are no data gaps in acute toxicity. Even though there is no information on acute toxicity in humans, there is no reason to believe that the low acute toxicity observed in experimental animals would not be relevant for human health.

Justification for classification or non-classification

The oral and dermal LD50 of C16 18FA-TEPA-compound were assessed to be > 2000 mg/kg bw. According to GHS Regulation EC No 1272/2008 no classification and labelling for acute toxicity is necessary.