1-Propanaminium, 2-hydroxy-N-(2-hydroxypropyl)-N,N-dimethyl-, esters with fatty acids, C16-18 (even numbered) and C18 unsatd., Me sulfates (salts)

Acute Toxicity: dermal

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

30 May 2008

Deviations:

no

Test guideline 2

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

Test material

Test material information

Constituent 1

Reference substance name:

MDIPA Esterquat C18 unsatd.

IUPAC Name:

MDIPA Esterquat C18 unsatd.

Details on test material:

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

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%

Test animals

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

Administration / exposure

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

Results and discussion

Effect levels

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.

Applicant's summary and conclusion

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