Fatty acids, C18 (even numbered) and C18 unsatd., reaction products with triethanolamine, di-Me sulfate quaternized

Endpoint summary

Description of key information

Oral LD50 (rat, m/f) > 4480 mg a.i./kg bw (EU Method B.1, oral: gavage); RL1; GLP; read-across: partially unsaturated TEA-Esterquat
Dermal LD50 (rat, m/f) > 2000 mg a.i./kg bw (OECD TG 402); RL1; GLP; read-across: partially unsaturated TEA-Esterquat

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have similar (eco)toxicological properties because
• they share structural similarities with common functional groups: One quaternised ethanolamine moiety, one to three, mainly two ester groups with a typical UVCB distribution with long-chain fatty acids of natural origin. The molecular structure is almost identical.
• they are manufactured from similar resp. identical precursors (triethanolamine, long-chain fatty acids, dimethyl sulphate) under similar conditions. Therefore common breakdown products via physical and biological processes, which result in structurally similar chemicals are evident
• A constant pattern in the changing of the potency of the properties across the TEA-Esterquats by chain-length and the grade of esterification is not observed, because the fatty acid chain-length distribution is too narrow and similar and the distribution of mono-, di-, and tri-esters is identical. Some variation caused by variation in C=C double bonds may occur and will be discussed at the relevant endpoint.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
See general justification for read-across attached to chapter 13 of this IUCLID file.

3. ANALOGUE APPROACH JUSTIFICATION
See general justification for read-across attached to chapter 13 of this IUCLID file.

4. DATA MATRIX
See general justification for read-across attached to chapter 13 of this IUCLID file.

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across source

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 4 480 mg/kg bw

Based on:

act. ingr.

Mortality:

No deaths occurred at the dose levels of 2000 and 5000 mg/kg during the observation period.

Clinical signs:

other: No clinical signs were observed in the animals treated at the dose level of 2000 mg/kg bw. Hypokinesia was noted only in the treated males at the dose level of 5000 mg/kg bw, 30 minutes and one hour after treatment, then in all the animals after 2 and 4 h

Gross pathology:

Due to the absence of macroscopic lesions, no organ samples were taken and no histological examination was performed.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 480 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:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have similar (eco)toxicological properties because
• they share structural similarities with common functional groups: One quaternised ethanolamine moiety, one to three, mainly two ester groups with a typical UVCB distribution with long-chain fatty acids of natural origin. The molecular structure is almost identical.
• they are manufactured from similar resp. identical precursors (triethanolamine, long-chain fatty acids, dimethyl sulphate) under similar conditions. Therefore common breakdown products via physical and biological processes, which result in structurally similar chemicals are evident
• A constant pattern in the changing of the potency of the properties across the TEA-Esterquats by chain-length and the grade of esterification is not observed, because the fatty acid chain-length distribution is too narrow and similar and the distribution of mono-, di-, and tri-esters is identical. Some variation caused by variation in C=C double bonds may occur and will be discussed at the relevant endpoint.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
See general justification for read-across attached to chapter 13 of this IUCLID file.

3. ANALOGUE APPROACH JUSTIFICATION
See general justification for read-across attached to chapter 13 of this IUCLID file.

4. DATA MATRIX
See general justification for read-across attached to chapter 13 of this IUCLID file.

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across source

Species:

rat

Strain:

other: CD, Crl. CD

Sex:

male/female

Type of coverage:

occlusive

Vehicle:

water

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 male and 5 female

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Observations were performed before and immediately, 5, 15, 30 and 60 min, as well as 3, 6 and 24 hrs
after administration, thereafter at least once daily.
Individual body weights were recorded before administration of the test substance and thereafter in weekly intervals up to the end of the study.
During the follow-up period, changes of skin and fur, eyes and mucous membranes, respiratory and circulatory function, autonomic and central
nervous system and somatomotor activity as well as behavior pattern were observed at least once a day until all symptoms subsided, thereafter
each working day. Attention was also paid to possible tremors, convulsions, salivation, diarrhea, lethargy, sleep and coma.
- Necropsy of survivors performed: All surviving animals were sacrificed, dissected and inspected macroscopically. All gross pathological changes
were recorded. No histopathology was carried out as no macroscopic findings were noted at necropsy.

other: skin irritation was scored according to the Draize scheme.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr.

Mortality:

no animal died

Clinical signs:

other: no signs of toxicity were observed

Gross pathology:

No marcroscopical changes were noted at necropsy.

Other findings:

No erythema or oedema were observed. All readings were 0.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

No experimental data are available for the assessment of the acute toxicity of the target substance C18 and C18 unsatd. TEA-Esterquat. However, reliable relevant data are available for the closely related source substance partially unsaturated TEA-Esterquat. A justification for read-across is attached to iuclid section 13.

 

Acute oral toxicity

In an acute oral toxicity study (according to EU Method B.1), 5 Sprague-Dawley rats/sex/dose were given single oral doses of 2000 or 5000 mg/kg bw  of partially unsaturated TEA-Esterquat (89.6 % a.i.) and observed for 14 days.

Oral LD50 Males and Females > 5000 mg/kg bw (nominal)

Oral LD50 Males and Females > 4480 mg/kg bw (based on a.i.)

No animal died. No clinical signs or effects on body weight were observed at 2000 mg/kg bw.

Hypokinesia was noted only in the treated males at the dose level of 5000 mg/kg bw, 30 minutes and one hour after treatment, then in all the animals after 2 and 4 hours. From day 2 to day 15, no clinical signs were observed at the dose level of 5000 mg/kg bw. These findings were accompanied by a slight slowed down of the body weight gain between day 1 and day 5 in the males at 5000 mg/kg bw. Normal weight gain was observed in the female 5000 mg/kg bw group. Gross pathological examinations at 14 days p.a. (terminal necropsy) revealed no test article-dependent findings.

 

Acute inhalation toxicity

According to REACH regulation, Annex XI, the conduct of an acute inhalation toxicity study is scientifically unjustified. The test substance has a low vapor pressure, so the potential for the unintended generation of inhalable forms such as aerosols is low. The most likely route of human exposure for workers and consumers is the dermal route.

The generation of dusts and aerosols is prevented by appropriate RMMs, and the substance is not used in spray applications. Thus, there is no concern with respect to respiratory irritation.

Given that acute toxicity is unlikely to occur based on low acute toxicity via the oral and dermal route, as well as on low exposure levels, testing by the inhalation route is scientifically not necessary according to REACH Regulation Annex XI 1 and 3.

 

Acute dermal 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 CD rats were dermally exposed to the partially unsaturated TEA-Esterquat suspended in water for 24 hours under an occlusive dressing to approx. 10 % of body surface area at doses of 2000 mg/kg bw. Animals then were observed for 14 days.

Dermal LD50          Males > 2000 mg/kg bw

                                  Females > 2000 mg/kg bw

                                 Combined > 2000 mg/kg bw

No mortality occurred in this limit test. No clinical signs were observed. No macroscopical changes were noted at gross pathological examinations at terminal necropsy. Normal weight gain was observed, except for one female rat. Its body weight gain appeared to be slightly reduced.

 

There are no data gaps for the endpoint acute toxicity. No human data are available. However, there is no reason to believe that these results from rat would not be applicable to humans.

 

Similar results were obtained with the source substance MDEA-Esterquat C16-18 and C18 unsatd., which is practically non-toxic based on the oral LD50 of >10.000 mg/kg bw and the dermal LD50 of >2000 mg/kg bw. These data are included into the dossier to demonstrate, that the substances have a similar toxicological profile.

Justification for classification or non-classification

Based on the available data, C18 and C18 unsatd. TEA-Esterquat does not need to be classified for acute toxicity according to regulation (EC) 1272/2008. Thus, no labelling is required.