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Administrative data

Description of key information

Based on the results of the studies and in line with its biocides assessment report, the oral and dermal LD50 values for the test substance are considered to be 350 and 2848 mg/kg bw respectively. Further, for the inhalation route, no hazard is expected as the identified inhalation hazard for aerosols of a quaternary ammonium compound mixture with MMAD ≤ 1 µm does not exist in practice.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From November 07, 1987 to December 03, 1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
other: Acute oral toxicity
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
other: undiluted test substance
Doses:
500, 794, 1,260 and 2,000 mg/kg bw
No. of animals per sex per dose:
10
Details on study design:
Dose selection was based upon the results of a range-finding study. Animals, 5 males and 5 females per dose group, were administered the undiluted test substance in a single oral dose by gavage. Animals were observed 1 and 4h after dosing and subsequently once daily for 14 d. Deaths and evidence of overt toxicity were recorded at each observation. Individual body weights were recorded on the d of treatment (Day 0), Days 7 and 14, and at death. All animals were subjected to gross necropsy examination for any macroscopic abnormalities.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 398 mg/kg bw
Based on:
test mat.
95% CL:
>= 298 - <= 542
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 358 mg/kg bw
Based on:
act. ingr.
95% CL:
>= 247 - <= 519
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 438 mg/kg bw
Based on:
act. ingr.
95% CL:
>= 288 - <= 665
Gross pathology:
Necropsy of decedents revealed abnormally red lungs, dark livers, haemorrhage and ulceration of the gastric mucosa and congestion of the small intestines. Major abnormalities seen at necropsy of animals killed at termination were white thickened areas of the non-glandular region of the stomach. Scattered white raised areas were also noted.
Interpretation of results:
other: Category 4 based on CLP criteria
Conclusions:
Under the study conditions, the rat LD50 of the test substance was considered to be 358 mg a.i./kg bw in males, 438 mg a.i./kg bw in f emales and 398 img a.i./kg bw in males and females combined.
Executive summary:

A study was conducted to determine the acute oral toxicity of the test substance, C12-16 ADBAC (50% active in water) according to OECD Guideline 401, in compliance with GLP. Based on the results of a range finding study, five male and five female rats per dose group weres administered the undiluted test substance (50% active) by gavage at dose levels of 500, 794, 1260 and 2000 mg/kg bw (i.e., equivalent to 250, 397, 630 and 1000 mg a.i./kg bw). Animals were observed 1 and 4 h after dosing and subsequently once daily for 14 days. Mortality and evidence of overt toxicity were recorded at each observation. Individual body weights were recorded on the day of treatment (Day 0), Days 7 and 14, and at termination. All animals were subjected to gross necropsy examination for any macroscopic abnormalities. One male treated with 1000 mg a.s./kg was found dead six h after dosing; all other deaths were noted one to two days after treatment. Surviving animals made expected bodyweight gains over the study period. Major signs of toxicity observed in both decedent and surviving animals were hunched posture, pilo-erection, decreased respiratory rate, diarrhoea, lethargy and ptosis. Ataxia was noted in animals treated with 397 mg a.s./kg bw and above. There were no survivors following treatment with 630 and 1000 mg a.s./kg. All surviving animals were normal three to four days after treatment.Necropsy of decedents revealed abnormally red lungs, dark livers, haemorrhage and ulceration of the gastric mucosa and congestion of the small intestines. Major abnormalities seen at necropsy of animals killed at termination were white thickened areas of the non-glandular region of the stomach. Scattered white raised areas were also noted. Under the study conditions, the LD50 was determined to be 358 mg a.i./kg bw (95% c.i: 247-519 mg a.s/kg bw) in males, 438 mg a.i./kg bw (95% c.i.: 288 – 665 mg a.s./kg bw) in females and 398 mg a.s./kg bw (95% c.i.: 298 – 542 mg a.s./kg bw) in male and females combined (Jones, 1986).

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
June, 1975
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given, comparable to scientific principles/standards.
Principles of method if other than guideline:
Acute oral toxicity was determined by oral administration of the test substance to nine dose groups of male and female rats and subsequent observations of clinical signs and mortality for 14 days. The LD50 was calculated from the mortality data recorded in the study.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Albino
Sex:
male/female
Details on test animals or test system and environmental conditions:
Test animals:
- Age at study initiation: Young adult rats
- Weight at study initiation: 200-300 g
- Fasting period before study: 24h
- Diet: Ad libitum
- Water: Ad libitum

Route of administration:
oral: gavage
Vehicle:
other: Propylene glycol for 1 mL/kg bw and lower doses and undiluted test substance for doses 2 mL/kg bw and above dose levels.
Details on oral exposure:
Vehicle:
- Amount of vehicle: Propylene glycol for 1 mL/kg bw and all lower doses. Higher doses were administered undiluted.






Doses:
0.25, 0.32, 0.40, 0.50, 1.0, 2.0, 4.0, 8.0 and 16.0 mL/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14d
- Frequency of observations: Daily
- Necropsy of survivors performed: No
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
0.43 mL/kg bw
Based on:
test mat.
95% CL:
>= 0.39 - <= 0.47
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
344 mg/kg bw
Based on:
act. ingr.
Mortality:
0/5, 0/5 and 1/5 animals died at 0.25, 0.32 and 0.40 mL/kg bw dose levels respectively. All animals in the higher dose groups (0.50 to 16.00 mL/kg bw) died during the study period.
Clinical signs:
other: All animals dosed at 0.25 to 0.50 mL/kg bw exhibited lethargy and slight to moderate diarrhea. The severity of the symptoms increased proportionately to the dose level received. Surviving animals returned to normal within 5 days of dosing. Animals dosed a
Interpretation of results:
other: Category 4 based on CLP criteria
Conclusions:
Under the conditions of the study, the LD50 of the test substance was 0.43 mL/kg bw (95% c.i.-0.39 - 0.47 mL/kg bw). After correcting for 100% active test substance, the LD50 was determined to be 344 mg a.i./kg bw.
Executive summary:

A study was conducted to determine the acute oral toxicity of the read across substance, C12-16 ADBAC (80% active), in albino rats. The test substance was administered to groups of five fasted male and female albino rats at 0.25, 0.32, 0.40, 0.50, 1.0, 2.0, 4.0, 8.0 or 16.0 mL/kg bw. Propylene glycol was used as vehicle for 1 mL/kg and all lower doses. Doses of 2 mL/kg bw and above were administered as received. Animals were observed for 14 d post-dosing. No post-mortem nor histopathological examinations were performed. All animals dosed with 0.25 to 0.50 mL/kg exhibited lethargy and slight to moderate diarrhea. The severity of the symptoms increased proportionately to the dose level received. Surviving animals returned to normal within 5 days. Animals dosed with 1.0 or 2.0 mL/kg were extremely lethargic. 0/5, 0/5 and 1/5 animals died at 0.25, 0.32 and 0.40 mL/kg bw, respectively. All animals in the higher dose levels died during the study period. Under the conditions of the study, the LD50 of the test substance is considered to be 0.43 mL/kg bw (95% c.i.:0.39 - 0.47 mL/kg bw) in males and females combined. After correcting for 100% active test substance, the LD50 is determined to be 344 mg a.i./kg bw (Wallace, 1975).

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
other: Acute oral toxicity
Limit test:
no
Species:
rat
Strain:
other: albino (not further specified)
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
water
Doses:
0.100, 0.215, 0.464, 1.00, 2.15 and 4.64 mL/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Statistics:
Data evaluated according to Weil CS, Biometrics 8, 1952, p.249
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 0.316 mL/kg bw
Based on:
test mat.
95% CL:
>= 0.205 - <= 0.488
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 316 mg/kg bw
Based on:
test mat.
Remarks on result:
other: the 95% confidence limits could not be calculated due to all or none response in females
Clinical signs:
other: Clinical signs noted were depression, convulsive movements depressed righting and placement reflexes, hypothermia of the extremities, excessive salivation, serosanguineous stains around the nose, rapid or laboured respiration or gasping, wheezing, diarrho

Table 1. Mortality data

Dose level

(mL/kg bw)

Concentration

(%)

Males

Females

Total

0.100

10

0/5

0/5

0/10

0.215

25

1/5

0/5

1/10

0.464

25

4/5

5/5

9/10

1.00

25

5/5

5/5

10/10

2.15

25

5/5

5/5

10/10

4.64

25

5/5

5/5

10/10

Interpretation of results:
other: Category 4 based on CLP criteria
Conclusions:
Under the study conditions and based on a LD50 value of 0.316 mL/kg bw for both male and female rats, taking into account a specific gravity of approximately 1 as well, the rat LD50 value of the test substance (purity not specified) would be approximately 316 mg/kg bw.
Executive summary:

A study was conducted to determine the acute oral toxicity of the test substance (purity not specified) according to OECD Guideline 401. The experiment was performed following a single oral administration to albino rats. Groups of ten fasted animals (five male and five female) were given a single oral dose of the test substance at 0.100, 0.215, 0.464, 1.00, 2.15 or 4.64 mL/kg. The animals were observed for 14 d after dosing and then killed for gross pathological examination. The total mortality at the doses tested was 0, 10, 90, 100, 100 and 100%. All surviving animals showed gains in body weight over the study period. Abnormalities at necropsy consisted in excessive salivation, diarrhoea, congested lungs, adrenals and kidneys, irritated gastrointestinal tracts and peritoneal walls, whitened spleens and livers and serous anguineous fluid in the stomach. No abnormalities were observed in survivors. The LD50 was found to be 0.316 (0.205 -0.488) mL/kg bw for males and females, respectively. For females, a 95% confidence interval could not be given due to the 'all-or-none' response. Under the study conditions and based on a LD50 value of 0.316 mL/kg bw for both male and female rats, taking into account a specific gravity of approximately 1 as well, the rat LD50 value of the test substance would be approximately 316 mg/kg bw (Anspach, 1976).

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
November to December, 1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Qualifier:
according to guideline
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
yes
Remarks:
7-d instead of 14-d observation period
GLP compliance:
yes
Remarks:
in house quality system
Test type:
up-and-down procedure
Limit test:
no
Species:
rat
Strain:
other: HC/CFY (remote Sprague-Dawley)
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
20, 400, 500, 640, 800, and 1000 mg/kg bw
No. of animals per sex per dose:
up and down procedure: 1 male and 1 female were tested at the estimated LD50. All subsequent decisions were taken based on the previous outcome(s). Dosing was continued until a total of 6 animals per sex had been dosed after reversal of the initial outcome.
Control animals:
no
Details on study design:
Duration of observation: 7-d
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
450 mg/kg bw
Based on:
test mat.
95% CL:
>= 351 - <= 578
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
469 mg/kg bw
Based on:
test mat.
95% CL:
>= 367 - <= 600
Mortality:
Mortality was observed at levels of 500 mg/kg bw and higher (males) or 400 mg/kg bw and higher (females)
Clinical signs:
other: Clinical signs included pilo-erection, hunched posture, abnormal gait, lethargy, pallor of the extremities, increases salivation, decreased respiratory rate, diarrhoea, ptosis and gasping. Recovery was apparently complete 3 to 7 days after dosing (except
Gross pathology:
Abnormalities at necropsy of animals that died consisted of haemorrhages or congestion of the lungs, pallor of the liver, kidneys and spleen and congestion of blood vessels in the stomach and/or intestines. Surviving animals showed no abnormalities at necropsy.

Table 1. Mortality data

Sex

Dose (mg/kg)

Mortality data on each occasion

No. of deaths

1

2

3

4

5

6

7

8

9

10

11

12

M

320

0

0/1

400

0

0

0/2

500

1

1

0

1

3/4

640

1

1

1

3/3

800

1

1/1

1000

1

1/1

F

320

0

0

0/2

400

1

0

0

1/3

500

1

1

2/2

640

0

1

1/2

800

1

1

2/2

1000

1

1/1

0 = animal survived; 1 animal died

Interpretation of results:
other: Category 4 based on CLP criteria
Conclusions:
Under the study conditions, the rat acute median lethal dose (LD50) of the test substance (unknown purity) was found to be 450 (351 -578) mg/kg bw and 469 (367 -600) mg/kg bw for males and females, respectively.
Executive summary:

A study was conducted to determine the acute oral toxicity of the test substance (purity not specified) according to OECD Guideline 425, in compliance with GLP (in house quality system). The experiment was performed with a single oral administration to HC/CFY (remote Sprague-Dawley) rats using the up-and-down method. Groups of fasted animals (1 male and 1 female at a time) were given a single oral dose of the test substance at levels between 320 and 1000 mg/kg bw. The animals were observed for 7 d after dosing and then culled for gross pathological examination. One male treated at 500 mg/kg was kept for 14 d. Mortality was observed at levels of 500 mg/kg bw and higher (males) or 400 mg/kg bw and higher (females). Clinical signs included piloerection, hunched posture, abnormal gait, lethargy, pallor of the extremities, increases salivation, decreased respiratory rate, diarrhoea, ptosis and gasping. Recovery was apparently complete 3 to 7 d after dosing (except for 1 male treated with 500 mg/kg bw (Day 15)). All surviving animals showed gains in body weight over the study period. Abnormalities at necropsy of animals that died consisted of haemorrhages or congestion of the lungs, pallor of the liver, kidneys and spleen and congestion of blood vessels in the stomach and/or intestines. Surviving animals showed no abnormalities at necropsy. Under the study conditions, the rat acute median lethal dose (LD50) of the test substance was found to be 450 (351 -578) mg/kg bw and 469 (367 -600) mg/kg bw for males and females, respectively (Kynoch, 1984).

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1969
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Reason / purpose for cross-reference:
reference to same study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
mouse
Strain:
other: Tyler's Original
Sex:
not specified
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
0.86, 1.04, 1.25, 1.50 and 1.79 mL/kg bw (corresponding to 0.024, 0.029, 0.035, 0.042 and 0.050 mL, respectively)
No. of animals per sex per dose:
10 (sex not specified)
Control animals:
no
Details on study design:
- A range finding study was carried out first. A 7-d observation period was used in the range findingh test.
1st trial: at 0.1, 0.5, 1.0, 1.5 and 2.0 mL: at all levels all animals (2/2) died
2nd trial: at 0.02 mL no (0/2) animals died; at 0.04, 0.06, 0.08 and 0.1 mL all animals (2/2) died
3rd trial: at 0.025 no (0/4) animals died; at 0.035 mL, 2/4 animals died.
- In the main study, a 14-d observation period was used.
Statistics:
LD50 calculated by the method of Litchfield and Wilcoxon, J. Pharm. Exp. Therap., 96:99,1949.
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
ca. 1.1 mL/kg bw
Based on:
test mat.
95% CL:
>= 0.961 - <= 1.25
Remarks on result:
other: 1.1 mL/kg bw is approximately equivalent to 550 mg a.i./kg bw
Mortality:
See 'Any information on results incl. tables'
Most deaths occurred within 48 hours after dosing.
Clinical signs:
other: Clinical signs included coma starting within 1-2 hours after dosing. Surviving animals generally appeared normal within 3 days

Table 1. Mortality

Dose level

(mL/kg bw)

Test amount

(mL)

Total

0.86

0.024

2/10

1.04

0.029

5/10

1.25

0.035

6/10

1.50

0.042

9/10

1.79

0.050

10/10

Interpretation of results:
other: Category 4 based on CLP criteria
Conclusions:
Under the study conditions and based on a LD50 value of 1.10 mL/kg bw in the mouse (sex not specified) and assuming a specific gravity close to 1, the LD50 value would be 1100 mg/kg bw (i.e., equivalent to 550 mg a.i./kg bw).

Executive summary:

A study was conducted to determine the acute oral toxicity of the test substance, C12-16 ADBAC (50% active in water) according to OECD Guideline 401. The experiment was performed following a single oral administration to mice (Tyler's Original). Groups of ten fasted animals (sex not specified) were given a single oral dose of 0.86, 1.04, 1.25, 1.50 or 1.79 mL/kg bw. The animals were observed for 14 d after dosing and then culled for gross pathological examination. Mortality was 20, 50, 60, 90 and 100%, respectively. Clinical signs included coma starting within 1-2 h after dosing. Most deaths occurred within 48 h after dosing. Surviving animals generally appeared normal within 3 d. Under the study conditions and based on a LD50 value of 1.10 mL/kg bw in the mouse and assuming a specific gravity close to 1, the LD50 value would be 1100 mg/kg bw (equivalent to 550 mg a.i./kg bw) (Anonymous, 1969).

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1967
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
other: Acute oral toxicity
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
0.125, 0.25, 0.50, 1.0 and 2.0 mL/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Animals were fasted overnight prior to dosing.
- 14d observation period.
- LD50 calculation by method of moving averages (Weil CS, Biometrics 8, 249, 1952)
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
0.354 mL/kg bw
Based on:
test mat.
95% CL:
>= 0.219 - <= 0.572
Remarks on result:
other: corresponds to 177 (110-286) mg/kg bw a.i.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
0.308 mL/kg bw
Based on:
test mat.
95% CL:
>= 0.198 - <= 0.477
Remarks on result:
other: corresponds to 154 (100-239) mg/kg bw a.i.
Mortality:
Mortality was 0, 40, 70, 100 and 100% in the five doses tested, respectively.
Gross pathology:
Abnormalities at necropsy consisted of congested kidneys

Table 1. Mortality data

Dose level (mL/kg bw)

Males

Females

Total

0.125

0/5

0/5

0/10

0.25

2/5

2/5

4/10

0.50

3/5

4/5

7/10

1.0

5/5

5/5

10/10

2.0

5/5

5/5

10/10

Interpretation of results:
study cannot be used for classification
Conclusions:
Under the study conditions, the rat acute median lethal dose (LD50) of the test substance was found to be 0.354 (0.219 -0.572) mL/kg bw and 0.308 (0.198 -0.477) mL/kg bw for males and females, respectively (i.e., equal to 177 (110-286) and 154 (100-239) mg/kg bw a.i., respectively).
Executive summary:

A study was conducted to determine the acute oral toxicity of the test substance, C12-16 ADBAC (50% active) according to OECD Guideline 401. The experiment was performed to in Sprague-Dawley rats. Groups of ten fasted animals (five male and five female) were given a single oral dose of the test substance at a dose level of 0.125, 0.25, 0.5, 1.0 or 2.0 mL/kg bw. The animals were observed for 14 d after dosing and then culled for gross pathological examination. Mortality was 0, 40, 70, 100 and 100%, respectively. All surviving animals showed gains in body weight over the study period. Abnormalities at necropsy consisted of congested kidneys. Under the study conditions, the rat acute median lethal dose (LD50) of the test substance was found to be 0.354 (0.219 -0.572) mL/kg bw and 0.308 (0.198 -0.477) mL/kg bw for males and females, respectively (equivalent to 177 (110-286) and 154 (100-239) mg/kg bw a.i., respectively) (West, 1967).

Endpoint:
acute toxicity: oral
Type of information:
other: Literature data
Adequacy of study:
supporting study
Study period:
1970
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Qualifier:
no guideline followed
Principles of method if other than guideline:
Acute LD50 reported in literature on various benzylalkyldimethyl ammonium compounds with varying chain lengths were complied.
GLP compliance:
not specified
Test type:
standard acute method
Key result
Dose descriptor:
LD50
Effect level:
>= 200 - <= 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Acute LD50 reported in literature on various benzylalkyldimethyl ammonium compounds with varying chain lengths

Results:

There are many LD50's reported in literature on various benzylalkyldimethyl ammonium compounds with varying chain
lengths which are all in the range between 200 and 2000 mg/kg bw (Harmful) (RTECS). However, at increasing alkyl chain
lengths beyond C16, LD50 increases (Cutler and Drobeck, 1970). The oral toxicity of aqueous test solutions is related to its
high irritancy to the mucosal surfaces of the GI-tract. This is consistent with the effects observed during pathology in
the selected key study, which are representative of the general observations in acute oral toxicity studies with
test substance. Observations in the deceased animals included red lungs, dark livers, haemorrhage and ulceration of the
gastric mucosa and congestion of the small intestines. Major abnormalities seen at necropsy of exposed animals killed at
termination were white thickened areas of the non-glandular region of the stomach. Scattered white raised areas were
also noted. The generally most observed clinical effects before death are respiratory and central nervous system
depression.

Interpretation of results:
study cannot be used for classification
Conclusions:
Acute LD50 reported in literature on various benzylalkyldimethyl ammonium compounds with varying chain lengths are all in the range between 200 and 2,000 mg/kg bw.
Executive summary:

There are many LD50's reported in literature on various benzylalkyldimethyl ammonium compounds with varying chain lengths which are all in the range between 200 and 2,000 mg/kg bw (RTECS) (1970). 

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
350 mg/kg bw
Quality of whole database:
The information required for this tonnage band is sufficiently met with the available data. The LD50 value corresponds to the mean value of the two key studies and is in line with the biocides assessment report. The main toxicity following acute oral exposure to the test substance relates to irritation and corrosivity rather than systemic effects.

Acute toxicity: via inhalation route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From February 21, 1990 to April 30, 1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
study with a mixture containing C12-16 ADBAC (40% active) and di C12-16 DMAC; 37.5% active)
Reason / purpose for cross-reference:
reference to same study
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPP 81-3 (Acute inhalation 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:
Test animals:
- Source: Charles River UK Ltd., Margate, UK
- Weight at study initiation: ca. 200 g on the d of exposure
- Housing: 5/sex in polypropylene cages with detachable wire mesh tops and floors
- Diet (e.g. ad libitum): ad lib
- Water (e.g. ad libitum): ad lib
- Acclimation period: at least 5 d

Environmental conditions:
- Temperature (°C): 18-24
- Humidity (%): 35-65

In-life dates: From 21 February, 1990 to 30 April, 1990
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
Generation of test atmosphere / chamber description
- Exposure apparatus: perspex whole body chamber (square section with pyramidal top)
- Exposure chamber volume: ca. 120L
- Method of holding animals in test chamber: wire mesh partitions to provide 10 separate animal compartments
- Source and rate of air: filtered and oil-free compressed air
- Method of conditioning air: dried
- System of generating particulates/aerosols: atomiser
- Method of particle size determination: cascade impaction (Andersen mini-sampler and Marple cascade impactor (model 296)
- Treatment of exhaust air: passage through a collection filter
- Temperature, humidity, pressure in air chamber: temperature measured at 30-min intervals (22-23°C), relative humidity not measured (reason: aqueous solution). However, as dried air was used and the test substance contained only 7.7% water, relative humidity could have been measured. Pressure in air chamber: not indicated. However, as the whole body chamber was placed in a hood, this is not as important.

Test atmosphere
- Brief description of analytical method used:
Five air samples (5 L for groups 2 and 4 (0.34 and 0.24 mg/L), 10L for group 3 (0.17 mg/L) were taken from the chamber during each exposure and the collected material was analysed to determine the concentration of the test substance in the chamber air. Each air sample was withdrawn, at 4 L per min, through a weighed glass fibre filter (Whatman GF/A) mounted in an open face filter holder. The volume of the air sample was measured with a wet-type gas meter. Two further air samples were taken using an Andersen mini-sampler or a series 290 Marple cascade impactor (Model 296), and the collected material was weighed to determine the particle size distribution of the test subtance. The samples were taken at approximately 1.5 and 3.5 h from the start of exposure. The filters from the open face sampler were transferred to extraction columns and compacted with a glass road. The test substance was eluted with five 2 mL portions of methanol into a 20 mL volumetric flask and diluted to volume with methanol.
The filters from the Andersen and Marple samplers were similarly treated t o give a final volume of 5 mL. The stages of the Andersenand Marple samplers were washed off with small amounts of methanol into 5 mL volurnentric flasks. The extracts were diluted with mobile phase to obtain solutions for HPLC-analysis with expected maximum concentrations of the test substance of 150 pg/mL.

- Samples taken from breathing zone: taken from the whole body chamber.

Vehicle: not used

- Test atmosphere (if not tabulated)
Concentrations:
0.34 mg/L (± 6%); nominal: 2.21 mg/L
0.17 mg/L (± 13%); nominal: 0.52 mg/L
0.24 mg/L (± 17%); nominal: 0.88 mg/L

- MMAD (mass median aerodynamic diameter) / GSD (geometric standard deviation):
0.34 mg/L : MMAD 1.9 µm, gsd 3.5
0.17 mg/L : MMAD 1.1 µm, gsd 2.7
0.24 mg/L : MMAD 0.8 µm, gsd 0.8
Analytical verification of test atmosphere concentrations:
yes
Remarks:
HPLC
Duration of exposure:
4 h
Concentrations:
0, 0.17, 0.24 and 0.34 mg/L
No. of animals per sex per dose:
5 per sex per concentration
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 21d
- Frequency of observations and weighing: observations continuously duringe exposure and at least twice daily thereafter; BW daily
- Food and water intake: daily
- Necropsy of survivors performed: yes
- Other examinations performed: lung weight, histopathology of lungs, liver and kidneys
Statistics:
LC50 determination by log probit method of Miller LC and Tainter ML, Proc. Soc. Exp. Bio. Med., 57(2),1944:261-264.
Key result
Sex:
male
Dose descriptor:
LC50
Effect level:
0.22 mg/L air (analytical)
95% CL:
>= 0.17 - <= 0.27
Exp. duration:
4 h
Remarks on result:
other: 220 mg/m3
Key result
Sex:
female
Dose descriptor:
LC50
Effect level:
0.28 mg/L air (analytical)
95% CL:
>= 0.21 - <= 0.35
Exp. duration:
4 h
Remarks on result:
other: 280 mg/m3
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
0.25 mg/L air (analytical)
95% CL:
>= 0.22 - <= 0.28
Exp. duration:
4 h
Remarks on result:
other: 250 mg/m3
Mortality:
control group: 0/10
0.17 mg/L: 1 male (1/10)
0.24 mg/L: 3 males and 1 female (4/10)
0.34 mg/L: 5 males and 4 females (9/10)
Clinical signs:
other: During exposure: The signs seen during exposure were considered to be consistent with inhalation of an irritant aerosol. Closing or partial closing of the eyes and exaggerated respiratory movement were seen in all rats exposed to the test subtance. Additi
Body weight:
There were moderate to marked decreases of body weight or reductions in the rate of body weight gain for up to 8d in male rats and for up to 14d in female rats following exposure at 0.17 mg/L or 0.24 mg/L. Subsequently weight gain for rats that survived exposure to the test substance was similar to that of the control rats.
Gross pathology:
The findings for rats that died as a result of exposure to the test substance were typified by congestion of the lungs, fluid in the trachea and gas-filled stomach. Macroscopic abnormalities in a proportion of rats that survived exposure to the test substance were a swollen appearance of the lungs and gas-filled stomachs and intestines.
Other findings:
The food and water consumption for the rat that survived exposure at 0.34 mg/L was variable and reduced. Food consumption was reduced for up to 12 d following exposure to the test substance at concentrations of 0.24 or 0.17 mg/L. The water consumption for these groups was reduced for up to 14d following exposure.

The lung weight to body weight ratio was increased, due to a high lung weight, for most rats that died as a result of exposure to ARMOBLEN 400 for a few decedents and the majority of the surviving rats was increased because of low body weight.

Histopathology
Group 2 (0.34 mg/L test substance)
Decedents
Treatment-related changes were seen in the 5 male and 4 female decedents. The distribution of these lesions was as follows:
focal alveolar wall necrosis in 3 males; diffuse congestion in 3 males and 4 females; eosinophilic material in alveoli in 5 males and 4
females; alveolitis in 2 males and 4 females; focal alveolar oedema in 1 male; perivascular oedema in 4 males.
Survivors
Treatment-related changes were seen in the single female rat surviving to the end of the observation period. These were as
follows: focal alveolitis; focal bronchiolitis; prominent bronchiolar goblet cells.

Group 3 (0.17 mg/L test substance)
Decedents
Treatment-related changes were seen in the single decedent male. These were as follows: diffuse congestion; eosinophilic materialin alveoli; alveolitis; focal alveolar oedema.
Survivors
Treatment-related changes were seen in one of the 4 males and in one of the 5 females surviving to the end of the observation
period. The distribution of these lesions was as follows: focal bronchiolitis in 1male; prominent bronchiolar goblet cells in 1 male;
foreign body giant cells in 1 male; focal alveolar haemorrhage in 1 female. A focus of emphysema was also seen in one surviving
female. The significance of this finding in a single animal is unclear, but possibility that it is related to treatment cannot be excluded.
No abnormalities were detected in 3 males and 3 females surviving to the end of the observation period.

Group 4 (0.24 mg/L test substance)
Decedents
Treatment-related changes were seen in the 3 male decedents and 1 female decedent. The distribution of these lesions was as
follows: diffuse or focal congestion in 2 males and 1 female; eosinophilic material in alveoli in 2 males and 1 female; alveolitis in 1
male and 1 female; focal alveolar oedema in 1 male; focal alveolar haemorrhage in 1 female; perivascular oedema in 1 female.
Survivors
Treatment-related change was seen in one of the two males and one of the 4 females surviving to the end of the observation
period. This lesion was: foreign body giant cells. No abnormalities were detected in 1 male and 3 females surviving to the end of theobservation period.

Comment from the authors
Treatment-related changes were found in the survivors from all groups. It is not possible to predict with certainty the progression of these lesions, but the changes were minimal and of a focal nature and it is possible that they would be resolved in the course of time leaving no permanent lesions.

For result tables, kindly refer to the attached background material section of the IUCLID.

Interpretation of results:
study cannot be used for classification
Conclusions:
Under the study conditions, the 4h-LC50 of the mixture was calculated to be 0.25 mg/L or 250 mg/m3.
Executive summary:

A study was conducted to determine the inhalation acute inhalation toxicity of a mixture of test substances (77.3% total active) containing cocobenzyldimethylamonium chloride (C12-16 ADBAC; 40% active) and dicocodimethylammonium chloride (di C12-16 DMAC; 37.5% active), according to OECD Guideline 403 and US EPA OPP 81 -3, in compliance with GLP. The experiment was performed in Sprague-Dawley rats. Four groups of ten rats (five males and five females) were given a single, 4 h whole body exposure at concentration levels of 0, 0.17, 0.24 and 0.34 mg/L. The animals were observed for 21 d after exposure and were then culled for gross and histopathological examination of the lungs. Bodyweight, food and water intake and lung weight were also determined. There were no deaths in the control group; one animal (male) died at 0.17 mg/L, four animals died at 0.24 mg/L (3 males, 1 female), and nine animals died at 0.34 mg/L (5 males, 4 females). Clinical signs of toxicity noted were (partial) closing of the eyes and exaggerated respiratory movement during exposure in all test groups, gasping and wetness around the mouth during exposure at 0.34 mg/L. Clinical signs were noted in survivors throughout the 21-day observation period. A decrease in body weight reduced weight gain, and reduced food and water intake were generally seen up to Day 14. Abnormalities noted at necropsy in survivors were increased relative lung weight, swollen appearance of the lungs and gas-filled stomach and intestines. Animals that died showed congestion of the lungs, fluid in the trachea, and gas-filled stomach. Histopathological lung changes in survivors generally consisted of focal alveolitis and bronchiolitis; changes in deceased animals generally consisted of focal alveolar wall necrosis, diffuse congestion, focal alveolar wall oedema and focal alveolar wall haemorrhage. Under the study conditions, the 4 h LC50 of the test substance was calculated to be 0.25 mg/L or 250 mg/m3 (95% CI: 0.22-0.28 mg/L or 220-280 mg/m3) i.e., equivalent to 129 mg/m3 for C12-16 ADBAC (Jackson, 1990).

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
Study period:
1989
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Principles of method if other than guideline:
Thirteen week subacute inhalation toxicity in the albino rat and golden hamster.
GLP compliance:
not specified
Species:
other: Rats and hamsters
Strain:
other: Albino and Syrian Golden
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Details on study design:
An inhalation toxicity study of an aerosolised hair conditioner containing 0.2% of a 50.0% test substance (effective concentration 0.1%)  was conducted with 12 female albino rats of the CD-strain and 12 Syrian Golden hamsters. Exposures were carried out in 500L dynamic flow inhalation chambers. The animals were exposed to the conditioner (9.9 mg/m3 of air) 5d a week (4 h/d) for 14 consecutive weeks. 
Key result
Dose descriptor:
LC0
Effect level:
> 9.9 mg/m³ air
Mortality:
There were no exposure-related deaths.
Body weight:
There were no significant differences in weight gain.
Gross pathology:
There were no exposure-related gross nor microscopic changes were attributed to test substance inhalation.
Other findings:
- Aerosol concentration in the chamber atmosphere was analysed.
- There were no significant differences in haematological values, and serum chemistry data between experimental and control groups.
Interpretation of results:
study cannot be used for classification
Conclusions:
Under the study conditions, the rat and hamster LC0 of the test substance was greater than 9.9 mg/m3.
Executive summary:

An inhalation toxicity study was conducted with an aerosolised hair conditioner containing 0.2% of a 50.0% test substance (effective concentration 0.1%) in 12 female albino rats of the CD-strain and in 12 Syrian Golden hamsters. Exposures were carried out in 500 L dynamic flow inhalation chambers. The animals were exposed to the conditioner (9.9 mg/m3 of air) 5 d a week (4 h/d) for 14 consecutive weeks. Aerosol concentration in the chamber atmosphere was analysed. There were no significant differences in weight gain, haematological values and serum chemistry data between experimental and control groups. There were no exposure-related deaths, and neither gross nor microscopic changes were attributed to test substance inhalation. Under the study conditions, the rat and hamster LC0 of the test substance was > 9.9 mg/m3 (CIR, 1989).

Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because the substance is classified as corrosive to the skin
Reason / purpose for cross-reference:
data waiving: supporting information
Reason / purpose for cross-reference:
data waiving: supporting information
Reason / purpose for cross-reference:
data waiving: supporting information
Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
study not available with pure substance; study with a mixture showed adverse effect observed; 4h LC50: 250 mg/m³ (or 129 mg a.i./m3). The identified inhalation hazard for aerosols with MMAD ≤ 1µm does not exists in practice. The substance is a sticky solid with a low vapour pressure. Due to its physical state and physical chemical properties, it is unlikely that it will form inhalable dust, mist or fumes when handled and used.

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1976
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
Levels tested were higher than the limit of 2000 mg/kg bw; groups of 4 male rabbits were used instead of 5; no verification in other sex
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
other: albino (not further specified)
Sex:
not specified
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Duration of exposure:
24h
Doses:
0.464, 1.00, 2.15, and 4.64 g/kg bw
No. of animals per sex per dose:
4 per dose (sex not indicated)
Control animals:
no
Statistics:
Statistics: Weil CS Biometrics 8, 249 (1952)
Key result
Dose descriptor:
LD50
Effect level:
1.78 mL/kg bw
Based on:
test mat.
95% CL:
>= 1.21 - <= 2.61
Key result
Dose descriptor:
LD50
Effect level:
1 780 mg/kg bw
Based on:
act. ingr.
Mortality:
0/4 at 0.464 mL/kg
0/4 at 1.00 mL/kg
3/4 at 2.15 mL/kg
4/4 at 4.64 mL/kg
Clinical signs:
other: Depression, diarrhoea, rapid or laboured respiration, emaciation, hypothermia, depressed righting and placement reflexes, purulent nasal discharge, excessive salivation, stains, hunched posture. Several of these changes persisted throughout the 14-d perio
Gross pathology:
Skin irritation effects consisted of moderate or marked spotted erythema, marked to extreme oedema, moderate to extreme necrosis, and spotted blanching. Damp and/or unkempt hair coats were seen. Skin effects were still present after 14 d. Abnormalities at necropsy consisted of congested kidneys, with moderately congested cortico-medullary junctions and pale or mottled livers, irritated gastro-intestinal tracts, congested adrenals, congested lungs, pallor of the stomach, depletion of body fat stores, and coriaceous skin tissue
Interpretation of results:
study cannot be used for classification
Conclusions:
Under the study conditions, the rat acute median lethal dose (LD50) of the test substance (purity not mentioned) was found to be 1.78 (1.21 -2.61) mL/kg bw in rabbits. Based on this LD50 value, taking into account an assumed specific gravity close to 1, the LD50 value would be ca. 1,780 mg/kg bw.
Executive summary:

A study was conducted to determine the dermal acute toxicity of the test substance (purity not specified) according to a method similar to OECD Guideline 402. The experiment was performed in albino rabbit. Groups of four animals were given a single dermal applications of 0.464, 1.00, 2.15 or 4.64 mL/kg bw. The animals were observed for 14 d after dosing and then culled for gross pathological examination. Mortality was 0, 0, 75 and 100%, respectively. Under the study conditions, the rat acute median lethal dose (LD50) of the test substance was found to be 1.78 (1.21 -2.61) mL/kg bw in rabbits. Based on this LD50 value, taking into account an assumed specific gravity close to 1, the LD50 value would be ca. 1780 mg/kg bw (Anspach, 1976).

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
1. In the study, 4 animals/sex/test group were used; however, the guideline recommends 5 animals of one sex in each test group. 2. Abraded and non abraded skin sites were used; however, guideline recommends unabraded skin. 3. Gross necropsy was not perfor
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
not specified
Sex:
male/female
Details on test animals or test system and environmental conditions:
Test animals:
- Weight at study initiation: 2.2 – 3.4 kg
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Test site
- Area of exposure: Back of animal (10% of body surface)
- Type of wrap if used: The test sites were covered with gauze and each animal was wrapped in a sleeve after application of the test substance
- Type of test site: Intact and abraded (half of the test animals in each sex, i.e., 2 animals/sex/group had their skin abraded on one side )

Removal of the test substance
- Washing (if done): After removal of the dressing, animals were washed with warm water and dried.
- Time after start of exposure: After 24h

Test material
- Amount(s) applied (volume or weight with unit): 3,4 and 5 mL/kg bw
- Concentration (if solution): Undiluted (as received)
- Constant volume or concentration used: yes

Duration of exposure:
24h
Doses:
3,4 and 5 mL/kg bw
No. of animals per sex per dose:
4
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14d
- Frequency of observations and weighing: The animals were observed for clinical signs, mortality and body weight (at the start of the experiment and at termination (Day 14)).
- Necropsy of survivors performed: No
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3.56 mL/kg bw
Based on:
test mat.
95% CL:
>= 3.01 - <= 4.2
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 730 mg/kg bw
Based on:
act. ingr.
Mortality:
Mortality observed at each dose levels:
3 mL/kg bw: 1/8
4 mL/kg bw: 6/8
5 mL/kg bw: 7/8

For details please refer to the attachment under 'Attached background material'
Clinical signs:
other: Severe erythema and oedema was observed post dosing at the sites of application for all animals in all groups. In the 3 mL/kg bw dose group (i.e., surviving animals), the erythema was followed by thickening of the skin and eschar formation across the back

Table 1:

Dose levels (ml/kg)

Mortality

Time to mortality

5 0

7/8

1, 2, 7 & 12 days

4.0

6/8

2, 3, 4 & 6 days

3.0

1/8

9 days

Table 2:

Dose levels (ml/kg)

Animal #

Bodyweight (kg)

Initial

Final

5

58

2.3

2.0

4

57A

2.8

2.7

61A

2.8

2.6

3

57B

3.0

2.6

58B

2.7

2.1

59B

3.2

3.1

60B

2.7

2.4

61B

2.6

2.4

63B

2.3

1.6

64B

2.6

2.0

Interpretation of results:
other: CLP criteria not met
Conclusions:
Under the conditions of the study, the acute dermal LD50 of the test substance was found to be 3.56 mL/kg bw (95% c.i.- 3.01 - 4.20 mL/kg bw). After correcting for 80%purity of the active substance, the LD50 was calculated to be 2730 mg/kg bw.
Executive summary:

A study was conducted to determine the acute dermal toxicity of the test substance, C12-16 ADBAC (80% active in water), according to a method similar to EPA OPPTS 870.1200. The experiment was performed in rabbits. The test substance was applied to twelve male and twelve female rabbits (4 animals/sex/test group) at dose levels of 3, 4 and 5 mL/kg bw (single application) on the abraded and intact skin of the back. The test sites were covered with gauze and each animal was wrapped in a sleeve after application for a 24 h period. After removal of the dressing, animals were washed with warm water and dried. The animals were observed for clinical signs and mortality for 14 d. Body weights were determined at the start of the experiment and at termination (Day 14). In the study, 1/8, 6/8 and 7/8 animals died at 3, 4 and 5 mL/kg bw, respectively. Decreases in bodyweight were observed in all surviving animals in all treatment groups.Severe erythema and oedema at site of application observed post dosing for all animals in all groups. In the 3 mL/kg dose group (i.e. surviving animals), the erythema was followed by thickening of the skin and eschar formation across the back. Under the conditions of the study, the acute dermal LD50 of the test substance is considered to be 3.56 mL/kg bw (95% c.i.- 3.01 - 4.20 mL/kg bw). After correcting for 80% purity of the active substance, the LD50 is calculated to be 2730 mg a.i./kg bw (Levenstein, 1977).

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1967
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
Levels tested were higher than the limit of 2000 mg/kg bw; groups of 4 male rabbits were used instead of 5; no verification in other sex.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
other: albino (not further specified)
Sex:
male
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Duration of exposure:
24h
Doses:
1.25, 2.50, 5.0 and 10.0 mL/kg bw
No. of animals per sex per dose:
4 males per dose
Control animals:
no
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
2.98 mL/kg bw
Based on:
test mat.
95% CL:
>= 1.75 - <= 5.05
Remarks on result:
other: on the basis of active product this corresponds to 1.49 (0.78-2.53) mL/kg bw
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
1 490 mg/kg bw
Based on:
act. ingr.
Mortality:
0/4 at 1.25 mL/kg
2/4 at 2.5 mL/kg
3/4 at 5.0 mL/kg
4/4 at 10.0 mL/kg
Gross pathology:
Abnormalities at necropsy consisted of congestion of the renal tubules.
Interpretation of results:
study cannot be used for classification
Conclusions:
Under the study conditions, the rat acute median lethal dose (LD50) of the test substance was found to be 1.49 (0.78-2.53) mL a.i./kg bw in rabbits. Based on this LD50 value, taking into account an assumed specific gravity close to 1, the LD50 value would be ca. 1,490 mg a.i./kg bw.
Executive summary:

A study was conducted to determine the acute dermal toxicity of the test substance (purity: 50%) according to a method similar to OECD Guideline 402. The experiment was performed in albino rabbit. Groups of four male animals were given a single dermal applications of 1.25, 2.5, 5.0 or 10.0 mL/kg bw. The animals were observed for 14 d after dosing and then culled for gross pathological examination. Mortality was 0, 50, 75 and 100%, respectively. Animals showed signs of severe skin irritation. The skin was endurated and severely oedematous with the area involved being greater than the site of application. This irritation persisted throughout the 14 d observation period. Under the study conditions, the rat acute median lethal dose (LD50) of the test substance was found to be 1.49 (0.78-2.53) mL/kg bw in rabbits. Based on this LD50 value, taking into account an assumed specific gravity close to 1, the LD50 value would be ca. 1490 mg/kg bw (West, 1967).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
2 848 mg/kg bw
Quality of whole database:
Due to the corrosive effect, there is a danger of irreversible damage to the skin upon exposure to the undiluted solution. Toxicity is secondary to the local tissue damage, rather than the result of percutaneously absorbed material.

Additional information

Oral:

Study 1:A study was conducted to determine the acute oral toxicity of the test substance, C12-16 ADBAC (50% active in water) according to OECD Guideline 401, in compliance with GLP. Based on the results of a range finding study, five male and five female rats per dose group were administered the undiluted test substance (50% active) by gavage at dose levels of 500, 794, 1260 and 2000 mg/kg bw (i.e., equivalent to 250, 397, 630 and 1000 mg a.i./kg bw). Animals were observed 1 and 4 h after dosing and subsequently once daily for 14 days. Mortality and evidence of overt toxicity were recorded at each observation. Individual body weights were recorded on the day of treatment (Day 0), Days 7 and 14, and at termination. All animals were subjected to gross necropsy examination for any macroscopic abnormalities. One male treated with 1000 mg a.s./kg was found dead six h after dosing; all other deaths were noted one to two days after treatment. Surviving animals made expected bodyweight gains over the study period. Major signs of toxicity observed in both decedent and surviving animals were hunched posture, pilo-erection, decreased respiratory rate, diarrhoea, lethargy and ptosis. Ataxia was noted in animals treated with 397 mg a.s./kg bw and above. There were no survivors following treatment with 630 and 1000 mg a.s./kg. All surviving animals were normal three to four days after treatment. Necropsy of decedents revealed abnormally red lungs, dark livers, haemorrhage and ulceration of the gastric mucosa and congestion of the small intestines. Major abnormalities seen at necropsy of animals killed at termination were white thickened areas of the non-glandular region of the stomach. Scattered white raised areas were also noted. Under the study conditions, the LD50 was determined to be 358 mg a.i./kg bw (95% c.i: 247-519 mg a.i./kg bw) in males, 438 mg a.i./kg bw (95% c.i.: 288 – 665 mg a.i./kg bw) in females and 398 mg a.i./kg bw (95% c.i.: 298 – 542 mg a.i./kg bw) in male and females combined (Jones, 1986).

Study 2:A study was conducted to determine the acute oral toxicity of the read-across substance, C12-16 ADBAC (80% active), in albino rats. The test substance was administered to groups of five fasted male and female albino rats at 0.25, 0.32, 0.40, 0.50, 1.0, 2.0, 4.0, 8.0 or 16.0 mL/kg bw. Propylene glycol was used as vehicle for 1 mL/kg and all lower doses. Doses of 2 mL/kg bw and above were administered as received. Animals were observed for 14 d post-dosing. No post-mortem nor histopathological examinations were performed. All animals dosed with 0.25 to 0.50 mL/kg exhibited lethargy and slight to moderate diarrhea. The severity of the symptoms increased proportionately to the dose level received. Surviving animals returned to normal within 5 days. Animals dosed with 1.0 or 2.0 mL/kg were extremely lethargic. 0/5, 0/5 and 1/5 animals died at 0.25, 0.32 and 0.40 mL/kg bw, respectively. All animals in the higher dose levels died during the study period. Under the conditions of the study, the LD50 of the test substance is considered to be 0.43 mL/kg bw (95% c.i.:0.39 - 0.47 mL/kg bw) in males and females combined. After correcting for 100% active test substance, the LD50 is determined to be 344 mg a.i./kg bw (Wallace, 1975).

Based on the above studies, same effect levels and toxicity potential were concluded in the biocide assessment report available on C12-16 ADBAC by RMS Italy (ECHA biocides assessment report, 2015). The RMS further remarked about the suitability of the test substance used in the Jones, 1986 study:“Although the test item is different, this result can be considered valid for C12-16-BKC, based on the similar mechanism for oral toxicity shown by QUATS with this alkyl chain length”.Lastly, a mean value of 350 mg/kg bw based on both the studies was taken forward as the key conclusion for the product authorization.

Study 3:A study was conducted to determine the acute oral toxicity of the test substance (purity not specified) according to OECD Guideline 401. The experiment was performed following a single oral administration to albino rats. Groups of ten fasted animals (five male and five female) were given a single oral dose of the test substance at 0.100, 0.215, 0.464, 1.00, 2.15 or 4.64 mL/kg. The animals were observed for 14 d after dosing and then killed for gross pathological examination. The total mortality at the doses tested was 0, 10, 90, 100, 100 and 100%. All surviving animals showed gains in body weight over the study period. Abnormalities at necropsy consisted in excessive salivation, diarrhoea, congested lungs, adrenals and kidneys, irritated gastrointestinal tracts and peritoneal walls, whitened spleens and livers and serous anguineous fluid in the stomach. No abnormalities were observed in survivors. The LD50 was found to be 0.316 (0.205 -0.488) mL/kg bw for males and females, respectively. For females, a 95% confidence interval could not be given due to the 'all-or-none' response. Under the study conditions and based on a LD50 value of 0.316 mL/kg bw for both male and female rats, taking into account a specific gravity of approximately 1 as well, the rat LD50 value of the test substance would be approximately 316 mg/kg bw (Anspach, 1976).

Study 4:A study was conducted to determine the acute oral toxicity of the test substance (purity not specified) according to OECD Guideline 425, in compliance with GLP (in house quality system). The experiment was performed with a single oral administration to HC/CFY (remote Sprague-Dawley) rats using the up-and-down method. Groups of fasted animals (1 male and 1 female at a time) were given a single oral dose of the test substance at levels between 320 and 1000 mg/kg bw. The animals were observed for 7 d after dosing and then culled for gross pathological examination. One male treated at 500 mg/kg was kept for 14 d. Mortality was observed at levels of 500 mg/kg bw and higher (males) or 400 mg/kg bw and higher (females). Clinical signs included piloerection, hunched posture, abnormal gait, lethargy, pallor of the extremities, increases salivation, decreased respiratory rate, diarrhoea, ptosis and gasping. Recovery was apparently complete 3 to 7 d after dosing (except for 1 male treated with 500 mg/kg bw (Day 15)). All surviving animals showed gains in body weight over the study period. Abnormalities at necropsy of animals that died consisted of haemorrhages or congestion of the lungs, pallor of the liver, kidneys and spleen and congestion of blood vessels in the stomach and/or intestines. Surviving animals showed no abnormalities at necropsy. Under the study conditions, the rat acute median lethal dose (LD50) of the test substance was found to be 450 (351 -578) mg/kg bw and 469 (367 -600) mg/kg bw for males and females, respectively (Kynoch, 1984).

Study 5:A study was conducted to determine the acute oral toxicity of the test substance, C12-16 ADBAC (50% active in water) according to OECD Guideline 401. The experiment was performed following a single oral administration to mice (Tyler's Original). Groups of ten fasted animals (sex not specified) were given a single oral dose of 0.86, 1.04, 1.25, 1.50 or 1.79 mL/kg bw. The animals were observed for 14 d after dosing and then culled for gross pathological examination. Mortality was 20, 50, 60, 90 and 100%, respectively. Clinical signs included coma starting within 1-2 h after dosing. Most deaths occurred within 48 h after dosing. Surviving animals generally appeared normal within 3 d. Under the study conditions and based on a LD50 value of 1.10 mL/kg bw in the mouse and assuming a specific gravity close to 1, the LD50 value would be 1100 mg/kg bw (equivalent to 550 mg a.i./kg bw) (Anonymous, 1969).

Study 6:A study was conducted to determine the acute oral toxicity of the test substance, C12-16 ADBAC (50% active) according to OECD Guideline 401. The experiment was performed to in Sprague-Dawley rats. Groups of ten fasted animals (five male and five female) were given a single oral dose of the test substance at a dose level of 0.125, 0.25, 0.5, 1.0 or 2.0 mL/kg bw. The animals were observed for 14 d after dosing and then culled for gross pathological examination. Mortality was 0, 40, 70, 100 and 100%, respectively. All surviving animals showed gains in body weight over the study period. Abnormalities at necropsy consisted of congested kidneys. Under the study conditions, the rat acute median lethal dose (LD50) of the test substance was found to be 0.354 (0.219 -0.572) mL/kg bw and 0.308 (0.198 -0.477) mL/kg bw for males and females, respectively (equivalent to 177 (110-286) and 154 (100-239) mg/kg bw a.i., respectively) (West, 1967).

There are also many LD50's reported in the literature on various benzyl alkyl dimethyl ammonium compounds with varying chain lengths which are all in the range between 200 and 2,000 mg/kg bw (RTECS) (1970). 

Therefore, based on the available information and in line with the biocides assessment report,the mean oral LD50 value of 350 mg/kg bw has been considered further for hazard/risk assessment.Overall, the main toxicity following acute oral exposure to the test substance relates to irritation and corrosivity rather than systemic effects.

Inhalation:

A study was conducted to determine the inhalation acute inhalation toxicity of a mixture of test substances (77.3% total active) containing cocobenzyldimethylamonium chloride (C12-16 ADBAC; 40% active) and dicocodimethylammonium chloride (di C12-16 DMAC; 37.5% active), according to OECD Guideline 403 and US EPA OPP 81 -3, in compliance with GLP. The experiment was performed in Sprague-Dawley rats. Four groups of ten rats (five males and five females) were given a single, 4 h whole body exposure at concentration levels of 0, 0.17, 0.24 and 0.34 mg/L. The animals were observed for 21 d after exposure and were then culled for gross and histopathological examination of the lungs. Bodyweight, food and water intake and lung weight were also determined. There were no deaths in the control group; one animal (male) died at 0.17 mg/L, four animals died at 0.24 mg/L (3 males, 1 female), and nine animals died at 0.34 mg/L (5 males, 4 females). Clinical signs of toxicity noted were (partial) closing of the eyes and exaggerated respiratory movement during exposure in all test groups, gasping and wetness around the mouth during exposure at 0.34 mg/L. Clinical signs were noted in survivors throughout the 21-day observation period. A decrease in body weight reduced weight gain, and reduced food and water intake were generally seen up to Day 14. Abnormalities noted at necropsy in survivors were increased relative lung weight, swollen appearance of the lungs and gas-filled stomach and intestines. Animals that died showed congestion of the lungs, fluid in the trachea, and gas-filled stomach. Histopathological lung changes in survivors generally consisted of focal alveolitis and bronchiolitis; changes in deceased animals generally consisted of focal alveolar wall necrosis, diffuse congestion, focal alveolar wall oedema and focal alveolar wall haemorrhage. Under the study conditions, the 4 h LC50 of the test substance was calculated to be 0.25 mg/L or 250 mg/m3 (95% CI: 0.22-0.28 mg/L or 220-280 mg/m3) or based on 77.3% active ingredient 0.32 mg a.i./L or 320 mg/m3 (Jackson, 1990).

In addition, an inhalation toxicity study was also identified from the literature source (CIR, 1989). This was conducted with an aerosolised hair conditioner containing 0.2% of a 50.0% test substance (effective concentration 0.1%) in 12 female albino rats of the CD-strain and 12 Syrian Golden hamsters. Exposures were carried out in 500 L dynamic flow inhalation chambers. The animals were exposed to the conditioner (9.9 mg/m3 of air) 5 d a week (4 h/d) for 14 consecutive weeks. Aerosol concentration in the chamber atmosphere was analysed. There were no significant differences in weight gain, haematological values and serum chemistry data between experimental and control groups. There were no exposure-related deaths, and neither gross nor microscopic changes were attributed to test substance inhalation. Under the study conditions, the rat and hamster LC0 of the test substance was > 9.9 mg/m3 (CIR, 1989).

Except for the above studies with a mixture of quaternary ammonium substances and a formulation, no well conducted with the pure test substance could be identified. However, in accordance with Annex VII, Section 8.5, Column 2, of the REACH regulation, the study does not need to be conducted because the substance is classified as corrosive to the skin. Further, the substance has a low vapour pressure (VP = 0.0058 Pa at 25 °C), which is below the cut-off of 0.01 Pa set for defining low volatility substances, as per the ECHA Guidance R.7a (2017). Therefore, due to its solid physical state and low VP, it is unlikely that it will form inhalable dust, mist or fumes when handled and used in solid form. In case inhalable forms of the substance (either pure or in aqueous solutions) are created under particular conditions (e.g., spraying, elevated temperature/pressure), appropriate risk management measures such as closed systems, exhaust ventilation or wearing of respirators are implemented to control exposure. Under such conditions, the risk to humans following inhalation exposure can be considered minimal and further testing involving vertebrate animals may be omitted, in accordance with Annex XI (1.2) of the REACH regulation. 

 

Dermal:

Study 1:A study was conducted to determine the acute dermal toxicity of the test substance, C12-16 ADBAC (80% active in water), according to a method similar to EPA OPPTS 870.1200. The experiment was performed in rabbits. The test substance was applied to twelve male and twelve female rabbits (4 animals/sex/test group) at dose levels of 3, 4 and 5 mL/kg bw (single application) on the abraded and intact skin of the back. The test sites were covered with gauze and each animal was wrapped in a sleeve after application for a 24 h period. After removal of the dressing, animals were washed with warm water and dried. The animals were observed for clinical signs and mortality for 14 d. Body weights were determined at the start of the experiment and at termination (Day 14). In the study, 1/8, 6/8 and 7/8 animals died at 3, 4 and 5 mL/kg bw, respectively. Decreases in bodyweight were observed in all surviving animals in all treatment groups. Severe erythema and oedema at site of application observed post dosing for all animals in all groups. In the 3 mL/kg dose group (i.e. surviving animals), the erythema was followed by thickening of the skin and eschar formation across the back. Under the conditions of the study, the acute dermal LD50 of the test substance is considered to be 3.56 mL/kg bw (95% c.i.- 3.01 - 4.20 mL/kg bw). After correcting for 80% purity of the active substance, the LD50 is calculated to be 2730 mg a.i./kg bw (Levenstein, 1977). However, the biocides assessment report available for C12-16 ADBAC, had reported the active ingredient corrected LD50 value as 2848 mg a.i./kg bw (ECHA biocides assessment report, 2015).

Study 2:A study was conducted to determine the acute dermal toxicity of the test substance (purity not mentioned) according to a method similar to OECD Guideline 402. The experiment was performed in albino rabbit. Groups of four male animals were given single dermal application of 1.25, 2.5, 5.0 or 10.0 mL/kg bw. The animals were observed for 14 d after dosing and then culled for gross pathological examination. Mortality was 0, 50, 75 and 100%, respectively. Animals showed signs of severe skin irritation. The skin was endurated and severely oedematous with the area involved being greater than the site of application. This irritation persisted throughout the 14-d observation period. Under the study conditions, the rat acute median lethal dose (LD50) of the test substance was found to be 1.49 (0.78-2.53) mL/kg bw in rabbits. Based on this LD50 value, taking into account an assumed specific gravity close to 1, the LD50 value would be ca. 1490 mg/kg bw (West, 1967).

Study 3:A study was conducted to determine the dermal acute toxicity of the test substance (purity not mentioned) according to a method similar to OECD Guideline 402. The experiment was performed in albino rabbit. Groups of four animals were given single dermal application of 0.464, 1.00, 2.15 or 4.64 mL/kg bw. The animals were observed for 14 d after dosing and then culled for gross pathological examination. Mortality was 0, 0, 75 and 100%, respectively. Under the study conditions, the rat acute median lethal dose (LD50) of the test substance was found to be 1.78 (1.21 -2.61) mL/kg bw in rabbits. Based on this LD50 value, taking into account an assumed specific gravity close to 1, the LD50 value would be ca. 1780 mg/kg bw (Anspach, 1976).

Therefore, based on the available information and in line with the biocides assessment report, the dermal LD50 value of 2,848 mg/kg bw has been considered further for hazard/risk assessment. Nevertheless, toxicity is secondary to the local tissue damage, rather than the result of percutaneously absorbed material.

Justification for classification or non-classification

Based on the oral and dermal LD50 values from the acute toxicity studies, the test warrants an ‘Acute Tox. 4; H302: harmful if swallowed’ classification for the oral route and ‘no classification’ for the dermal route according to EU CLP criteria (Regulation EC 1272/2008). In addition, for the inhalation route, although the test substance is classified to be corrosive (see section 5.3) and this drives its mechanism of action of toxicity, its inherent low vapour pressure prohibits the occurrence of respiratory irritation or corrosion by vapour. Therefore, it does not warrant additional labelling as: EUH071 — ‘Corrosive to the respiratory tract’ according to EU CLP criteria (Regulation EC 1272/2008).

Further, the available data does not show an indication that classification for STOT-SE cat 1 or 2 is indicated. For STOT-SE Cat 3: C16 TMAC or QAS substances are not narcotic.