1-Propanaminium, 2-hydroxy-N-(2-hydroxypropyl)-N,N-dimethyl-, esters with C18-unsatd. fatty acids, Me sulfates (salts)

Endpoint summary

Description of key information

Acute oral toxicity: LD50 > 2000 mg/kg bw, OECD Guideline 423, GLP compliant
Acute dermal toxicity: LD50 > 2000 mg/kg bw, OECD Guideline 402, GLP compliant

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:

2010-11-30 to 2010-12-15

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:

(30 May 2008)

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: 1-Propanaminium, 2-hydroxy-N-(2-hydroxypropyl)-N,N-dimethyl-, esters with fatty acids, C18 unsatd., Me-sulfates (salts)
- Physical state: liquid
- Analytical purity: 100%

Species:

rat

Strain:

other: White Wistar, HsdCpb: WU

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: approx. 11 weeks
- Weight at study initiation: 209.9 ± 6.6 g
- Fasting period before study: overnight before application and 3 h thereafter
- Housing: 3/cage in Makrolon type IV cages
- Diet (e.g. ad libitum): Rats/mice maintenance diet 1324, Altromin, Lage, Germany, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3°C
- Humidity (%): 30-70%
- Air changes (per hr): 8/h
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: not given; sponsor had informations on toxicity of similar substances that justified a limit test.

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: clinical signs immediately, 1, 3 h after administration, daily thereafter except Saturday + Sunday (day 10 + 11); weighing day 0, 7, 14
- Necropsy of survivors performed: yes

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr.

Remarks on result:

other: No mortality was observed

Mortality:

0/6 animals died during the observation period

Clinical signs:

other: No clinical signs were observed.

Gross pathology:

The necropsy of all animals showed no macroscopically visible test substance related pathologic organ findings.

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 of MDIPA Esterquat C18 unsatd. 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 (30 May 2008), 6 fasted, approx. 11 weeks old female White Wistar, HsdCpb: WU rats were given a single oral dose of undiluted MDIPA Esterquat C18 unsatd. (100% a.i.) at a limit dose of 2000 mg/kg bw and observed for 14 days.

No animal died during the observation period, no clinical signs were observed. The body weight development of the animals was positive and within normal range. The necropsy at the end of the observation period showed no macroscopically visible test substance related pathologic organ findings.

Oral LD50 Females > 2000 mg/kg bw

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

In addition to the key study, no adverse effects also for other species and for other routes at highest dose / concentation tested. Suppporting information on similar substances also showed no advese effects.

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

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:

30 May 2008

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: 1-Propanaminium, 2-hydroxy-N-(2-hydroxypropyl)-N,N-dimethyl-, esters with fatty acids, C18 unsatd., Me-sulfates (salts)
- Physical state: liquid
- Analytical purity: 100%

Species:

rat

Strain:

other: White Wistar, HsdCpb: WU

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: approx. 8 weeks
- Weight at study initiation: 182.1 ± 8.0 g (female), 219.2 ± 8.7 g (male)
- Fasting period before study: no
- Housing: individually in Makrolon cages type III
- Diet (e.g. ad libitum): Rats/mice maintenance diet 1324, Altromin, Lage, Germany, ad libitum
- Water (e.g. ad libitum): tap water from municipal source, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3°C
- Humidity (%):30 - 70 %
- Air changes (per hr): 8/h
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

other: sesame oil

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: approx. 10% body surface area
- Type of wrap if used: covered with a gauze pad which was held in place by strips of Micropore; the dressing was bandaged with Acrylastic and fixed with Leukoplast

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no washing; residual test substance together with the dressing was removed after 24 hours exposure time

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw applied as 50% solution in sesame oil

VEHICLE
- Lot/batch no. (if required): 068K0150, Sigma

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical signs: immediately, 1 h and 4 h after application, daily thereafter except on Saturdays and Sundays; weighing: before dosing, day 7 and 14
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr.

Remarks:

(test substance was applied as a 50% solution due to the strong irritation properties )

Remarks on result:

other: No mortality was observed

Mortality:

No animal died during the observation period.

Clinical signs:

other: No symptoms of systemic toxicity were observed.

Gross pathology:

The necropsy of all animals 14 days after application showed no macroscopically visible test substance related pathologic organ findings.

Other findings:

Moderate signs of skin irritation Iike erythema, edema were observed at the site of application in all animals from 24 h after application on. Starting day 6 after application, incrustation and desquamation were recorded at the application sites. The severity of the observed skin lesions declined with time but the irritant response was not totally reversible within 14 days after application in all animals. Incrustation and desquamation were still present in 4/5 males and 4/5 females on day 14.

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal LD50 of MDIPA Esterquat C18 unsatd. in rats 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 (30 May 2008), groups of young adult White Wistar, HsdCpb: WU rats (5/sex)were dermally exposed to MDIPA Esterquat C18 unsatd. (50% in sesame oil) 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.

Results from an in vivo skin irritation assay in rabbits indicated that the undiluted test substance causes strong irritation to the skin of animals. However, according to information from a sensitisation test with guinea pigs a 50% dilution in sesame oil was tolerated without strong skin effects. Thefefore, the test substance was applied in this acute dermal toxicity test as 50% dilution in sesame oil. Moderate signs of skin irritation Iike erythema and edema were observed at the site of application in all animals from 24 h after application on. Starting day 6 after application, incrustation and desquamation were recorded at the application sites. The severity of the observed skin lesions declined with time but the irritant response was not totally reversible within 14 days after application in all animals. Incrustation and desquamation were still present in 4/5 males and 4/5 females on day 14.

 

No animal died during the observation period. No symptoms of systemic toxicity were observed. The body weight development of the animals was positive 7 and 14 days after application. However, body weight gain was slightly lower than expected. The necropsy of all animals 14 days after application showed no macroscopically visible test substance related pathologic organ findings.

 

Dermal LD50 Combined > 2000 mg/kg bw

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

key study Rel. 1, GLP available, no adverse effects also for other routes at highest dose/conc. tested

Additional information

Acute oral toxicity

In an acute oral toxicity study according to OECD guideline 423 (17 December 2001) and EU method B.1 tris (30 May 2008), 6 fasted, approx. 11 weeks old female White Wistar, HsdCpb: WU rats were given a single oral dose of undiluted MDIPA Esterquat C18 unsatd. (100% a.i.) at a limit dose of 2000 mg/kg bw and observed for 14 days. No animal died during the observation period, no clinical signs were observed. The body weight development of the animals was positive and within normal range. The necropsy at the end of the observation period showed no macroscopically visible test substance related pathologic organ findings. The oral LD50 for female rats was > 2000 mg/kg bw.

 

This finding was supported by an acute oral toxicity study similar to OECD guideline 401, with mice. Fasted, 20±2 g mice of Tylers Original Strain (5/sex) were given a single oral dose of MDIPA Esterquat C18 unsatd. (75% a.i.) at a dose of 6.6 mL/kg bw (corresponding to 5.0 mL/kg bw adjusted to purity) and observed for 14 days. 1/10 animals died on day 4. Slight signs of toxicity were observed in the high dose group. However, all animals appeared asymptomatic 24 h after administration.

The oral LD50 for male and female mice was > 5000 mL/kg bw (as a.i.). Based on a density of 0.987 g/cm³ this corresponds to an LD50 of > 4935 mg a.i./kg bw.

 

The source substances MDEA-Esterquat C16-18 and C18 unsatd.  and MDIPA-Esterquat C16-18 and C18 unsatd. were of similarly low oral toxicity. These supporting studies are included in the dossier to justify the read-across for higher tier toxicity endpoints and to complete the toxicological profiles of the substances.

In an acute oral toxicity study comparable to now deleted OECD guideline 401, groups of fasted, WISW rats 5 males and 5 females were given a single oral dose of MDEA-Esterquat  40% w/w a.i. in oleum arachidis at a dose of 10,000 mg/kg bw. No mortality occurred in this test. The combined LD 50 in this study was >10000 mg/kg bw.

 

In an acute oral toxicity Irwin dose-range study comparable to now deleted OECD guideline 401, groups of fasted, CD-1 mice 4 males were given a single oral dose of MDEA-Esterquat C16-18 and C18 unsatd. 40% w/w in oleum arachidis at a dose of 316, 1000, 3160 and 10 000  mg/kg bw and observed for 7 days. The oral LD50 in males was >10000 mg/kg bw.

 

In an acute oral toxicity study according to OECD guideline 423 (17 December 2001) and EU method B.1 tris (30 May 2008), 6 fasted, approx. 10 weeks old female Wistar Crl:WI (Han) rats were given an oral dose of MDIPA-Esterquat C16-18 and C18 unsatd. (100% a.i.) at a limit dose of 2000 mg/kg bw administered as two dosages of 1000 mg/kg bw within 4 h. Animals were then observed for 14 days. The oral LD 50 was > 2000 mg/kg bw in this study.

 

Acute dermal toxicity

In an acute dermal toxicity study according to OECD guideline 402 (24 February 1987) and EU method B.3 (30 May 2008), groups of young adult White Wistar, HsdCpb: WU rats (5/sex)were dermally exposed to MDIPA Esterquat C18 unsatd. (50% in sesame oil) 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.

Results from an in vivo skin irritation assay in rabbits indicated that the undiluted test substance causes strong irritation to the skin of animals. However, according to information from a sensitisation test with guinea pigs a 50% dilution in sesame oil was tolerated without strong skin effects. Thefefore, the test substance was applied in this acute dermal toxicity test as 50% dilution in sesame oil. Moderate signs of skin irritation Iike erythema and edema were observed at the site of application in all animals from 24 h after application on. Starting day 6 after application, incrustation and desquamation were recorded at the application sites. The severity of the observed skin lesions declined with time but the irritant response was not totally reversible within 14 days after application in all animals. Incrustation and desquamation were still present in 4/5 males and 4/5 females on day 14. No animal died during the observation period. No symptoms of systemic toxicity were observed. The body weight development of the animals was positive 7 and 14 days after application. However, body weight gain was slightly lower than expected. The necropsy of all animals 14 days after application showed no macroscopically visible test substance related pathologic organ findings.

The dermal LD50 for male and female rats was > 2000 mg/kg bw.

 

Also the source substance used for read-across MDEA-Esterquat C16-18 and C18 unsatd. was of low dermal toxicity:

In an acute dermal toxicity study (comparable to OECD guideline 402), groups of 3 male and female New Zealand White rabbits were dermally exposed to MDEA-Esterquat C16-18 and C18 unsatd. (40 % a.i) in oleum arachidis for 24 hours to10 x 15 cm of body surface area at doses of 2000 mg/kg bw. Animals then were observed for 14 days. No mortality occurred in this limit test. The dermal LD50 was > 2000 mg/kg bw in this study.

 

Acute inhalation toxicity

Conduct of an acute inhalation study is regarded unnecessary for the following reasons: MDEA and MDIPA based Esterquats share the property of having a very low vapour pressure. MDIPA Esterquat C18 unsatd. has a vapour pressure of approx. 5E-06 hPa at 20°C excluding inhalation exposure by vapours.

Aerosols may be generated during use in car wash booths. However, the margin of safety for this exposure scenario is sufficiently high to make additional animal tests obsolete – for details on exposure please see the respective exposure scenarios.

With respect to irritation, skin irritation effects have not been observed at 6% of the active ingredient. The substance concentration in spray applications is <0.1 to 0.2%, 30 to 60 fold below the irritation threshold. Therefore, also for irritative effects on the respiratory tract, a sufficient margin of safety is expected for this application. From the absence of a skin sensitisation potential for this substance class, respiratory sensitisation is not expected. 

For workers with a risk to aerosol inhalation with the undiluted test substance, personal protective equipment will be in place to avoid respiratory exposure.

 

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.

 

Based on the available information, the acute toxicity of MDIPA Esterquat C18 unsatd. is low for all three routes of administration. 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

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