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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

The acute oral LD50 is 1157 mg/kg bw. The acute dermal LD50 of the read-across substance DDAC is 3342 mg a.s./kg bw, equivalent to 5.56 mL/kg bw  test substance (assuming a density of 1).

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:
2 April 2001 to 4 May 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
Male and female Sprague-Dawley rats were obtained from Ace Animals, Inc., Boyertown, Pennsylvania, USA, aged 8-12 weeks and weighing 204-234 g (males) and 150-184g (females). The animals were housed singly in suspended stainless steel cages, the temperature and relative humidity were 18-23°C and 35-72%, respectively, lighting was provided according to a 12 hour light/dark cycle. The rats were provided with food (Purina Rodent Chow #5012) ad libitum, except during fasting prior to dosing (approximately 18 hours pre-dose and 3.5 hours after dosing). Water (filtered tap water)was provided ad libitum. Rats in the range finding screen were acclimatised for 29 days; the test animals were acclimated for 10 days.
In-life dates of main test animals: 20 April to 4 May, 2001.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Individual doses were calculated based on initial body weights, taking into account the specific gravity of the test substance. Each rat received the appropriate amount of test substance as a single administration by gavage.
Doses:
500, 1000, 2000, 4000 mg/kg bw.
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
A range finding screen was conducted prior to the main test for selection of dose levels, with four male and four female rats. The test substance was administered to fasted rats at 500 and 2000 mg/kg bw. The animals were observed for 7 days after dosing. One male and one female from the 2000 mg/kg bw group died (50% mortality). Based on the range finding, dose levels of 500, 1000, 2000 and 4000 mg/kg bw were selected for the main test.
The observation period was 14 days. The rats were observed for clinical signs and mortality, and body weights were recorded. Gross necropsy was performed on rats that died during the study and on survivors at the end of the 14 day observation period.
Statistics:
Moving Average Method was used to calculate the LD50.
Preliminary study:
Range-finding: one male and one female from the 2000 mg/kg bw group died (50% mortality).
Sex:
male
Dose descriptor:
LD50
Effect level:
972 mg/kg bw
Based on:
test mat.
95% CL:
>= 798 - <= 1 237
Sex:
female
Dose descriptor:
LD50
Effect level:
1 414 mg/kg bw
Based on:
test mat.
95% CL:
>= 845 - <= 2 367
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 157 mg/kg bw
Based on:
test mat.
95% CL:
>= 833 - <= 1 519
Mortality:
There were no mortalities at 500 mg/kg bw. There was a dose-related increase in mortality in the remaining groups:
1000 mg/kg bw: 4/10 (3/5 males; 1/5 females), 2000 mg/kg bw: 9/10 (5/5 males; 4/5 females), and 4000 mg/kg bw: 10/10 (5/5 males; 5/5 females). Mortalities in the 1000 and 2000 mg/kg bw groups occurred within 7 days of administration, and within 2 days of administration in the 4000 mg/kg/ bw group.
Clinical signs:
other: 500 mg/kg bw: most rats exhibited ocular discharge, hunched posture, hypoactivity, ano-genital staining, soft faeces, diarrhoea and/or reduced faecal volume. All animals recovered by Day 10. 1000 mg/kg bw: clinical signs in the 3 males and 1 female that
Gross pathology:
No gross abnormalities were observed in the animals that survived to study termination. Necropsy of the animals that died following administration of 1000 mg/kg bw revealed discolouration of the lungs, liver and intestines and/or gaseous distention of the intestines. Necropsy of the animals that died following administration of 2000 mg/kg bw revealed discolouration of the lungs, liver and/or intestines, and in one male the stomach was filled with fluid and the lungs were oedematous. Necropsy of the 4000 mg/kg bw group revealed discolouration of the lungs, liver and/or intestines, oedema of the lungs, fluid-filled stomach, gaseous distention of the intestines and/or rigor mortis.
Other findings:
No other findings were reported.

Table 1. Group incidence of mortality

Dose level
(mg/kg bw)

Mortality#

Male

Female

Total

500

0/5

0/5

0/10

1000

3/5

1/5

4/10

2000

5/5

4/5

9/10

4000

5/5

5/5

10/10

# Number dead/total number in group

Table 2. Group incidence of clinical signs (number affected/total number in group)

Clinical signs

Dose level (mg/kg bw)

500

1000

2000

4000

Ocular discharge

1/10

2/10

1/10

0/10

Hunched/abnormal posture

1/10

2/10

7/10

3/10

Hypoactivity

1/10

5/10

10/10

10/10

Ano-genital staining

6/10

7/10

9/10

5/10

Soft faeces

2/10

4/10

2/10

0/10

Diarrhoea

1/10

3/10

9/10

5/10

Reduced faecal volume

7/10

10/10

5/10

3/10

Facial staining

0/10

1/10

2/10

0/10

Irregular/shallow breathing

0/10

1/10

4/10

6/10

Piloerection

0/10

1/10

2/10

1/10

Distended abdomen

0/10

1/10

0/10

0/10

Prone

0/10

0/10

1/10

6/10

 Table 3. Group mean body weight (g)


Day of study

Dose level (mg a.s./kg)

500

1000

2000

4000

M

F

M

F

M

F

M

F

0

215

175

221

176

219

165

213

170

7

235

209

235

187

a/d

178

a/d

a/d

14

294

244

305

221

a/d

211

a/d

a/d

M: male

F: female

a/d: all dead

Table 4. Group incidence of gross findings at necropsy

Gross findings#

                          Dose level (mg a.s./kg)

500

1000

2000

4000

No abnormalities

10/10

6/10

1/10

0/10

Lungs

Slightly red

0/10

0/10

2/10

2/10

Slightly red, oedematous

0/10

0/10

1/10

4/10

Moderately red

0/10

4/10

7/10

4/10

Liver

Discolouration

0/10

4/10

5/10

8/10

Intestines

Slightly red

0/10

0/10

1/10

4/10

Slightly red, gaseous distention

0/10

2/10

0/10

0/10

Red, gaseous distention

0/10

0/10

0/10

4/10

Red

0/10

0/10

5/10

0/10

Red/green

0/10

2/10

0/10

0/10

Black/green/red

0/10

0/10

3/10

0/10

Stomach

Filled with fluid

0/10

0/10

1/10

6/10

General appearance

Rigor mortis

0/10

0/10

0/10

4/10

# Gross abnormalities seen only in decedents
Number of animals affected/total number in group

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The combined sexes LD50 is 1157 mg/kg bw. The test substance is therefore classified as H302: Harmful if Swallowed according to Regulation (EC) No 1272/2008.
Executive summary:

The acute oral toxicity of Bardap 26 was determined in male and female Sprague-Dawley rats. The test substance was administered by gavage to groups of 5 rats/sex at doses of 500, 1000, 2000 and 4000 mg/kg bw. The rats were observed for clinical signs, mortality and body weights changes for 14 days after administration. Gross necropsy was performed on rats that survived to study termination and those that died during the study.

There was a dose-related increase in mortality; 3/5 males and 1/5 females in the 1000 mg/kg bw groups died within 7 days of administration; 5/5 males and 4/5 females in the 2000 mg/kg bw group died within 7 days of administration; all animals (5 males and 5 females) in the 4000 mg/kg bw group died within 2 days of administration. Clinical signs included hypoactivity, irregular/shallow breathing, ano-genital staining and diarrhoea. Gross necropsy findings in decedents included discoloured liver, red lungs, black/green/red intestines and fluid-filled stomach. The LD50 for male rats was 972 mg/kg (95% confidence limits: 798-1237 mg/kg bw); the LD50 for female rats was 1414 mg/kg bw (95% confidence limits: 845-2367 mg/kg bw); and the LD50 for both sexes combined was 1157 mg/kg bw (95% confidence limits: 833-1519 mg/kg bw). The substance is therefore classified as H302: Harmful if Swallowed according to Regulation (EC) No 1272/2008.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 157 mg/kg bw
Quality of whole database:
Guideline study

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
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
Study period:
March 1987
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
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
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.
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.
Preliminary study:
Not applicable.
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.

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)

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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
3 342 mg/kg bw
Quality of whole database:
A Guideline- and GLP-compliant study is available for a read-across substance. It is also noted that the substance is corrosive, therefore additional testing is not required.

Additional information

Some of the data summarised in this section are based on Didecyldimethylammonium Chloride a chemical and structural analogue of the test substance. In view of the chemical and structural similarities, it is considered that the available data are adequate for read-across.

Acute Oral Toxicity

The lowest determined oral LD50 value for Bardap 26 is 1157 mg/kg bw (Merkel, 2001). There was a dose-related increase in mortality. Clinical signs included hypoactivity, irregular/shallow breathing, ano-genital staining and diarrhoea. Gross necropsy findings in decedents included discoloured liver, red lungs and fluid-filled stomach. The substance is classified as ‘H302: Harmful if swallowed’ according to Regulation (EC) No 1272/2008.

Acute Inhalation Toxicity

The test substance is not volatile as the vapour pressure is 1.8x10-6 Pa. Thus, inhalation is not considered a potential route of exposure.

Acute Dermal Toxicity

The rabbit acute dermal LD50 of Didecyldimethylammonium Chloride is 3342 mg/kg bw, equivalent to 5.56 mL/kg bw administered test substance assuming a density of 1 (Siglin, 1987). The test substance caused skin irritation at the dose site in all animals. Rabbits died at the two highest dose levels. There was a dose-related reduction in body weight. The highest administered dose caused a pale cortex of the kidneys in almost half of the animal of the group and a distension of the atrium and/or ventricles in 3/10 animals. The test substance was corrosive to dermal tissue and only moderately toxic systemically by the dermal route. Clinical symptoms and pathological evidence of cardiac toxicity were not observed and the cardiac muscle did not appear to be a primary target organ after dermal exposure. Therefore classification for dermal toxicity is not required according to Regulation (EC) No 1272/2008.


Justification for selection of acute toxicity – oral endpoint
Only one study is available for this endpoint.

Justification for selection of acute toxicity – inhalation endpoint
N,N-Didecyl-N-methyl-poly(oxyethyl)ammonium Propionate is not volatile (vapour pressure: 1.8E-6 Pa²) so the potential for the generation of inhalable forms is low, therefore exposure to humans via the inhalatory route is unlikely to occur. In addition, the results of the skin irritation study indicate that the substance is corrosive, thus it is considered that a study is not justified on animal welfare grounds.

Justification for classification or non-classification

According to Regulation (EC) No 1272/2008, the substance is classified as 'H302: Harmful if swallowed' on the basis of an acute oral toxicity study. No classification is required for acute dermal toxicity (LD50 = 3342 mg/kg bw); data are not available for acute inhalation toxicity.