Miristalkonium chloride

Repeated dose toxicity: dermal

Administrative data

Endpoint:

short-term repeated dose toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

March 06, 1972

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1972

Report date:

1972

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

A study was conducted to determine the short term repeated dose dermal toxicity of the test substance following application of 1 mL/kg bw (i.e., equivalent to 0.8 mg/kg bw/day) and 4 mL/kg bw (i.e., equivalent to 3.2 mg/kg bw/day) of the test solution in rabbits for 20 days.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Miristalkonium chloride

EC Number:

205-352-0

EC Name:

Miristalkonium chloride

Cas Number:

139-08-2

Molecular formula:

C23H42N.Cl

IUPAC Name:

N-benzyl-N,N-dimethyltetradecan-1-aminium chloride

impurity 1

Reference substance name:

Dimethyl(tetradecyl)amine

EC Number:

204-002-4

EC Name:

Dimethyl(tetradecyl)amine

Cas Number:

112-75-4

Molecular formula:

C16H35N

IUPAC Name:

n,n-dimethyltetradecan-1-amine

impurity 2

Reference substance name:

N,N-Dimethyltetradecan-1-amine--hydrogen chloride (1/1)

Cas Number:

2016-47-9

Molecular formula:

C16H36ClN

IUPAC Name:

N,N-Dimethyltetradecan-1-amine--hydrogen chloride (1/1)

Test material form:

solid

Remarks:

Powder

Specific details on test material used for the study:

8 oz jar containing a white powder
Lot no.: 263-S
Test substance: Myristyl dimethyl benzyl ammonium chloride
Purity: 99.1%
Dilution of 800 ppm in water was made, based on a 100% active material and used in test

Test animals

Species:

rabbit

Strain:

not specified

Sex:

male/female

Administration / exposure

Type of coverage:

occlusive

Vehicle:

water

Details on exposure:

TEST SITE
- Area of exposure: Backs and flanks
- % coverage: 10% of total body area
- Type of wrap if used: Rubberized fabric
- Time intervals for shavings or clipplings: Hair was clipped from their backs and flanks. One half of each test area was abraded as required, while the remainder was left intact

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No washing
- Time after start of exposure: 27 days

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1 mL/kg (0.8 mg/kg bw/day) and 4 mL/kg (3.2 mg/kg bw/day)
- Constant volume or concentration used: Yes

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

Dose groups:
1 mL/kg = 0.8 mg/kg bw/day
4 mL/kg = 3.2 mg/kg bw/day

Duration of treatment / exposure:

20 d

Frequency of treatment:

once a day

No. of animals per sex per dose:

1 animal per sex per dose

Control animals:

yes

Examinations

Observations and examinations performed and frequency:

Food, fluid intake, excretions, behavior and appearance of the animals were observed daily. The animals were weighed, as required. Blood and urine studies were performed at the beginning of the test, at the 20 d interval end prior to autopsy.

Sacrifice and pathology:

At autopsy, gross findings were made and tissues retained for histological examination.

Results and discussion

Results of examinations

Clinical signs:

not examined

Dermal irritation:

effects observed, treatment-related

Description (incidence and severity):

Minimal erythema was observed in the treated rabbits on day 5, with minimal edema evident on day 9 in the animals receiving the larger dose. In the same group the erythema became more pronounced on day 11, and persisted with minimal edema at those levels through the rest of the treatment interval. At the lower dose level (1 mL/kg bw) minimal hyperemia showed occasional correction with no edema. On day 15 in the same group hyperemia increased slightly in intensity, but became minimal on day 19 and remained that way to day 21. Minimal edema was observed in the 1 mL/kg bw animals on day 17 through the end of treatment. In the control rabbits minimal hyperemia was observed in the rabbits from day 11 through day 21. All rabbits showed complete recovery of dermal irritation within 4 days after cessation of treatment.

Mortality:

not examined

Body weight and weight changes:

no effects observed

Description (incidence and severity):

Weights increases were normal.

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

Food intake was all within normal parameters at all times.

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

no effects observed

Description (incidence and severity):

Water intake was all within normal parameters at all times.

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Description (incidence and severity):

Hematology studies were all within normal parameters at all times.

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Description (incidence and severity):

Urine analysis studies were all within normal parameters at all times.

Behaviour (functional findings):

no effects observed

Description (incidence and severity):

At no time did any of the rabbits manifest abnormal behavior or appearance.

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

no effects observed

Description (incidence and severity):

Gross findings at autopsy were not significant.

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

no effects observed

Description (incidence and severity):

The histological findings in the treated rabbits were identical to those in the controls.

Histopathological findings: neoplastic:

not examined

Effect levels

1

Key result

Dose descriptor:

NOAEL

Remarks:

Sysmetic toxicity

Effect level:

ca. 3.2 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

behaviour (functional findings)

body weight and weight gain

food consumption and compound intake

gross pathology

haematology

histopathology: non-neoplastic

urinalysis

water consumption and compound intake

2

Key result

Dose descriptor:

LOAEL

Effect level:

ca. 0.8 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

dermal irritation

Target system / organ toxicity

Key result

Critical effects observed:

yes

Lowest effective dose / conc.:

0.8 mg/kg bw/day

System:

integumentary

Organ:

skin

Treatment related:

yes

Dose response relationship:

not specified

Relevant for humans:

not specified

Any other information on results incl. tables

Table 1: Histopathology results

Rabbit	Dose 800 ppm	Findings
1 F	1 mL/kg	As in control
2 M	1 mL/kg	As in control
3 F	4 mL/kg	As in control
4 M	4 mL/kg	As in control
5 F	4 mL/kg	Water control
6M	4 mL/kg	Water control

Dose groups:

1 mL/kg = 0.8 mg/kg bw/day

4 mL/kg = 3.2 mg/kg bw/day

 

Table 2: Dermal reactions 24 h after each set of applications

Day of treatment		1F	2M	3F	4M	5F*	6M*
2	Erythema	0	0	0	0	0	0
	Edema	0	0	0	0	0	0
3	Erythema	0	0	0	0	0	0
	Edema	0	0	0	0	0	0
4	Erythema	0	0	0	0	0	0
	Edema	0	0	0	0	0	0
5	Erythema	0	0	0	1	0	0
	Edema	0	0	0	0	0	0
6	Erythema	1	0	1	1	0	0
	Edema	0	0	0	0	0	0
7	Erythema	1	0	1	1	0	0
	Edema	0	0	0	0	0	0
8	Erythema	1	1	1	1	0	0
	Edema	0	0	0	0	0	0
9	Erythema	1	1	1	1	0	0
	Edema	0	0	0	1	0	0
10	Erythema	0	1	2	2	0	0
	Edema	0	0	0	1	0	0
11	Erythema	1	1	2	2	1	1
	Edema	0	0	0	1	0	0
12	Erythema	0	0	2	2	1	1
	Edema	0	0	1	1	0	0
13	Erythema	0	0	2	2	1	1
	Edema	0	0	1	1	0	0
14	Erythema	0	0	2	2	0	1
	Edema	0	0	1	1	0	0
15	Erythema	0	0	2	2	0	1
	Edema	0	0	1	1	0	0
16	Erythema	0	0	2	2	0	1
	Edema	0	0	1	1	0	0
17	Erythema	0	0	2	2	0	1
	Edema	0	0	1	1	0	0
18	Erythema	0	0	2	2	0	1
	Edema	0	0	1	1	0	0
19	Erythema	1	1	2	2	0	1
	Edema	1	1	1	1	0	0
20	Erythema	1	1	2	2	1	1
	Edema	1	1	1	1	0	0
21	Erythema	1	1	2	2	1	1
	Edema	1	1	1	1	0	0

Applicant's summary and conclusion

Conclusions:

Under study conditions, NOAEL for systemic effects and LOAEL for dermal irritation (local effect) were considered to be 3.2 mg/kg bw/day and 0.8 mg/kg bw/day respectively. 

Executive summary:

A study was conducted to determine the short term repeated dose dermal toxicity of the test substance, C14 ADBAC (Purity 99.1%), according to the procedure described in Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, published by the Association of Food and Drug Officials of the United States. In the study, 1 mL/kg bw (i.e., equivalent to 0.8 mg/kg bw/day) and 4 mL/kg bw (i.e., equivalent to 3.2 mg/kg bw/day) of the 800 PPM solution of the test substance were applied over 10% of the total body surface (Hair clipped back and flank) of the rabbits (one rabbit per sex per dose level) for 20 days. After each application of test substance the torsos of the test animals were wrapped with a rubberized fabric to prevent grooming by the rabbits with possible inhalation or ingestion of test product. Survivors were maintained for two weeks after the last application when all animals were autopsied, as required by the reference. Food, fluid intake, excretions, behaviour and appearance of the animals were observed daily. The animals were weighed, as required. Blood and urine studies were performed at the beginning of the test, at the 20 d interval end prior to autopsy. At autopsy, gross findings were made and tissues retained for histological examination. At no time did any of the rabbits manifest abnormal behaviour or appearance. Food and water intake, excretions, blood and urine studies were all within normal parameters at all times. Weights increases were normal. Minimal erythema was observed in the treated rabbits on day 5, with minimal edema evident on day 9 in the animals receiving the larger dose. In the same group the erythema became more pronounced on day 11, and persisted with minimal edema at those levels through the rest of the treatment interval. At the lower dose level (1 mL/kg bw = 0.8 mg/kg bw/day) minimal hyperemia showed occasional correction with no edema. On Day 15 in the same group hyperemia increased slightly in intensity, but became minimal on Day 19 and remained that way to Day 21. Minimal edema was observed in the 1 mL/kg bw animals on Day 17 through the end of treatment. In the control rabbits minimal hyperemia was observed in the rabbits from day 11 through Day 21. All rabbits showed complete recovery of dermal irritation within 4 d after cessation of treatment. Gross findings at autopsy were not significant. The histological findings in the treated rabbits were identical to those in the controls. Under study conditions, NOAEL for systemic effects and LOAEL for dermal irritation (local effect) were considered to be 3.2 and 0.8 mg/kg bw/day respectively (Luy and Frances, 1972).