(3-methacrylamidopropyl)trimethylammonium chloride

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2011-09-20 to 2011-11-10

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study. GLP.

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:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

adopted 24 Feb 1987

Deviations:

yes

Remarks:

1 animal was subject to reduced exposure time ranging between >4 to 24 hours

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted 30 May 2008

Deviations:

yes

Remarks:

1 animal was subject to reduced exposure time ranging between >4 to 24 hours

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

adopted August 1998

Deviations:

yes

Remarks:

1 animal was subject to reduced exposure time ranging between >4 to 24 hours

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

(3-methacrylamidopropyl)trimethylammonium chloride

EC Number:

257-182-1

EC Name:

(3-methacrylamidopropyl)trimethylammonium chloride

Cas Number:

51410-72-1

Molecular formula:

C10 H21 N2 O. Cl

IUPAC Name:

trimethyl-[3-(2-methylprop-2-enoylamino)propyl]azanium chloride

Test material form:

other: aqueous solution

Details on test material:

- Name of test material (as cited in study report): N-Trimethylammoniumpropyl methacrylamide-chloride

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: males: approx. 13 weeks; females: approx. 14 weeks
- Weight at study initiation: males: 246-257 g; females: 208-228 g
- Fasting period before study: no
- Housing: individual IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding (lot no. 091110)
- Diet (e.g. ad libitum): Altromin 1324 maintenance diet for rats and mice (lot no. 1956)
- Water (e.g. ad libitum): tap water, sulphur acidified to a pH value of approx. 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals)
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%):55 ± 10%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 2011-09-20 to 2011-11-10

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Remarks:

test substance in aqueous solution as delivered by the sponsor

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: at least 10%
- Type of wrap if used: gauze-dressing and non-irritating tape, fixed with additional dressing in suitable manner

REMOVAL OF TEST SUBSTANCE
- Washing (if done): tap water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Concentration (if solution): 50.6% (correction factor used for correct dose application: 1.976)

VEHICLE
Test substance applied as delivered by the sponsor

Duration of exposure:

24 hours (except for one female rat which unwrapped itself overnight, thus leading to a reduced duration of exposure of 4-24 hours)
For the animal which unwrapped itself, no signs of toxicity and significant dermal irritation were observed. As at the 4 h control observation the dressing was tight on all animals, it is very likely that the animal unwrapped itself clearly after the 4 h period. It can be expected that this animal has been exposed to the test item partially also by the oral route, while grooving, in addition to the dermal route.
It is concluded that the abbreviated exposure period has no effect on the overall result and the classification of the test item, and that a sufficient estimation of the dermal toxicity is ensured.
The validity of the study is not affected and according to animal welfare reasons it was decided not to repeat the study.

Doses:

2000 mg/kg bw (corrected for a.i.)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical observation several times on day of dosing (at least once during first 30 minutes and with special attention given during the first 4 hours post-dose). Symptoms were recorded as soon as noticed. Thereafter, daily observations for clinical signs until end of observation period. All abnormalities were recorded. Animals were weighed on day 1 (prior to application of dose) and on day 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed:
-- In case of gross pathological changes, tissues were preserved for a possible histopathological evaluation.
-- The treated areas of skin were examined daily for signs of primary skin irritation. Signs of erythema and oedema were assessed using the scoring system laid down in OECD Guideline 404, adopted 24th April 2002.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr.

Remarks on result:

other: mortaliy 0/10

Mortality:

All animals survived until the end of the observation period of 14 days.

Clinical signs:

other: No signs of systemic toxicity were observed

Gross pathology:

With the exception of acute injection of blood vessels in the abdominal region, which is due to the euthanasia injection, no specific gross pathological changes were recorded for any animal.

Other findings:

Signs of irritation:
- Erythema grade 1 was observed in 1 of 5 female animals. Eschar, desquamation and scratches were observed in 1 of 5 female animals.
- No signs of irritation were found for the male animals.
All signs of irritation were reversible within the observation period.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) 1272/2008

Conclusions:

The LD50-value for acute dermal toxicity of MAPTAC is > 2000 mg/kg bw.

Executive summary:

In an acute dermal toxicity study according to OECD guideline 402 (adopted 24th Feb, 1987), EU Method B.3 (adopted 30 May 2008), 5 male and 5 female young adult WISTAR Crl: WI(Han) rats were dermally exposed to MAPTAC for 24 hours under a semiocclusive dressing to approx. 10% of body surface area at doses of 2000 mg/kg bw (based on active ingredient). Animals then were observed for 14 days.

No animal died. Erythema grade 1 was observed in 1 of 5 female animals. Eschar, desquamation and scratches were observed in 1 of 5 female animals. No signs of irritation were found for the male animals. All signs of irritation were reversible within the observation period. No clinical signs of systemic toxicity were observed. Weight gain was positive and within normal range, except for 3 female rats which temporarily lost weight in the first week. No macroscopic substance related pathologic organ findings were noted during necropsy.

Dermal LD₅₀

Males > 2000  mg/kg bw

Females > 2000  mg/kg bw

Combined > 2000  mg/kg bw

 

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