Poly(oxy-1,2-ethanediyl), α-[2-(dide- cylmethylammonio)ethyl]- .omega.- hydroxy-, propanoate (salt) (Bardap 26)

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

March 1987

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPP 81-2 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

DDAC

IUPAC Name:

DDAC

Constituent 2

Reference substance name:

1-Decanaminium, N-decyl-N,N-dimethyl-, chloride

IUPAC Name:

1-Decanaminium, N-decyl-N,N-dimethyl-, chloride

Constituent 3

Reference substance name:

Didecyldimethylammonium chloride

EC Number:

230-525-2

EC Name:

Didecyldimethylammonium chloride

Cas Number:

7173-51-5

Molecular formula:

C22 H48 N.Cl

IUPAC Name:

N-decyl-N,N-dimethyldecan-1-aminium chloride

Constituent 4

Reference substance name:

N,N-Didecyl-N,N-dimethylammonium Chloride

IUPAC Name:

N,N-Didecyl-N,N-dimethylammonium Chloride

Details on test material:

The test substance was described as a yellow liquid. Storage at room temperature. The test substance is hydrolytically and photolytically stable under the study conditions and has been shown to be stable in aqueous alcohol and alcohol/aqueous solutions for extended periods, e.g. at least 7 years under standard laboratory conditions.

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

The test animals were male and female New Zealand White young adult rabbits, obtained from Gota-Frisco Farms, Ohio. The animals were housed individually in suspended stainless steel cages in an environmentally controlled room with a 12 hour light/dark cycle. Feed (Agway Prolab Rabbit Ration) and fresh water were provided ad libitum. The rabbits were allowed to acclimatise to the laboratory conditions for at least 5 days. Only healthy animals were selected for the study. The rabbits weighed 2.245-3.09 kg (males) and 2.195-2.956 kg (females) at study initiation.
In-life dates were 3 to 17 March, 1987.

Administration / exposure

Type of coverage:

not specified

Vehicle:

other: 10% v/v ethanol and water

Details on dermal exposure:

The test substance (in vehicle: 10% v/v ethanol in water) was applied dermally to the rabbits. The volume of liquid administered to each animal was adjusted based on the 80% content of the active ingredient, to achieve the specified treatment level. The vehicle was prepared fresh prior to dosing.
On the day prior to dosing, the fur was clipped from the dorsal area of the trunk of each rabbit using small animal clippers. The exposed area on each animal measured approximately 12 x 20 cm (approximately 10% of the animal's total body surface). The following day, the test substance was applied uniformly over the exposed skin. An occlusive binder (8 ply gauze dressing, a layer of rubber dam and several wrappings of 3 inch Elastoplast tape) was secured around the trunk of the animal immediately after treatment. The dressing was removed after 24 hours and residual test material was wiped from the skin using clean gauze and distilled water.

Duration of exposure:

24 hours

Doses:

Doses were prepared taking into account the purity of the test substance (80%): 0, 552, 1104, 3328 and 4448 mg a.s./kg bw, corresponding to dose volumes 0.69, 1.38, 4.16 and 5.56 ml/kg, respectively. 5.56 ml/kg bw of the vehicle (10% v/v ethanol and water) was applied to the controls.

No. of animals per sex per dose:

5/sex/dose

Control animals:

yes, concurrent vehicle

Details on study design:

Healthy animals were allocated to treatment groups randomly. The exposure period was 24 hours, and the observation period was 15 days. The rabbits were observed daily for clinical signs and mortality. Bodyweights were recorded on Days 1, 8 and 15. Gross necropsy was performed on animals that died during the study and those that survived to study termination.

Statistics:

Probit Analysis (Finney, 1997) was used in LD50 calculations.

Results and discussion

Preliminary study:

Not applicable.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

5.56 mL/kg bw

Based on:

test mat.

Remarks on result:

other: Actual dose administered, assuming a density of 1

Mortality:

No mortalities occurred at concentrations below 3328 mg a.s./kg bw. 3/5 males and 2/5 females died at a concentration of 3328 mg a.s./kg bw and 5/5 males and 3/5 females died at a concentration of 4448 mg a.s./kg bw.

Clinical signs:

other: No clinical signs were observed in 552 mg/kg bw group. The most common observations at 1104 mg/kg bw and above was reduced faeces, ocurring within 72 hours of dosing and persisting for 1-4 days. Additional observations in one 1104 mg/kg bw animal included

Gross pathology:

Necropsy findings were minimal. At a dose rate of 4448 mg a.s./kg the test substance caused a pale cortex of the kidneys in 4/10 animals and a distention of the atrium and/or ventricles in 3/10 animals. One animal in the 3328 mg/kg bw group had a heavily pigmented gel in the large intestines.

Other findings:

The test substance caused eschar formation in all animals at all doses at the treatment site within 24 hours.

Any other information on results incl. tables

Table 1. Mortality data

			Study day
Sex	Test subs. conc. (mg a.s./kg bw)	No. Animals	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	Total
M	552	5	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	1104	5	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3328	5	0	0	0	0	0	2	0	0	0	0	0	1	0	0	0	3
	4448	5	0	0	0	1	3	1	-	-	-	-	-	-	-	-	-	5
F	552	5	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	1104	5	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3328	5	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	2
	4448	5	0	0	0	0	1	0	1	1	0	0	0	0	0	0	0	3

 

Table 2. Clinical Signs

Clinical Signs	Test substance concentration (mg a.s./kg bw)
	0	552	1104	3328	4448
Soft stools and/or faecal stain	1/10	0/10	1/10	5/10	1/10
Few faeces	1/10	3/10	9/10	10/10	10/10
Laboured breathing	0/10	0/10	0/10	1/10	4/10
Prostration	0/10	0/10	0/10	4/10	2/10
Convulsions	0/10	0/10	0/10	0/10	1/10
Thrashing in cage	0/10	0/10	0/10	0/10	1/10
Rales	0/10	0/10	0/10	0/10	1/10
Nasal discharge	0/10	0/10	2/10	1/10	1/10
Activity decreased	0/10	0/10	1/10	10/10	10/10
Tremors	0/10	0/10	0/10	1/10	3/10
Ataxia	0/10	0/10	0/10	1/10	3/10
Emaciated	0/10	0/10	0/10	7/10	5/10
Dark material around mouth	0/10	0/10	1/10	2/10	1/10
Urine stain	0/10	0/10	0/10	2/10	1/10
Mucoid material in litter pan	0/10	0/10	2/10	3/10	0/10

 

Table 3. Mean body weight data (kg)

		Study day
Sex	Test substance concentration (mg a.s./kg)	1	8	15
Male	552	2.832	2.806	2.988
	1104	2.667	2.431	2.606
	3328	2.730	1.868	2.057
	4448	2.770	n/d	n/d
Female	552	2.641	2.575	2.415
	1104	2.502	2.222	2.415
	3328	2.583	1.819	1.818
	4448	2.678	1.894	1.905

n/d no data (all animals were dead)

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 (both sexes) was calculated as 3342 mg/kg bw (5.56 mL/kg bw test substance, assuming a density of 1)

Executive summary:

The acute dermal toxicity of DMD10AC (80% Didecyldimethylammonium Chloride) was evaluated in male and female New Zealand White rabbits. The test substance was applied dermally to the skin of the rabbits for 24 hours, at the following concentrations: 0, 552, 1104, 3328 and 4448 mg/kg bw. The rabbits were observed for 15 days post-exposure for clinical signs of toxicity, mortality and bodyweight changes. Gross necropsy was performed on survivors at study termination and on rabbits that died during the study.

The test substance caused skin irritation at the dose site in all animals. 5 rabbits died at a concentration of 3328 mg/kg bw and 8 rabbits died at a concentration of 4448 mg/kg bw. There was a dose-related reduction in body weight. At a dose rate of 4448 mg/kg bw the test substance caused a pale cortex of the kidneys in 4/10 animals and a distention of the atrium and/or ventricles in 3/10 animals. The LD₅₀ (both sexes) was calculated as 3342 mg/kg bw (equivalent to 5.56 mL/kg bw test substance, assuming a density of 1) with confidence limits 0 - 4293 mg/kg bw, and therefore no classification is required.

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