Registration Dossier

Toxicological information

Acute Toxicity: dermal

Currently viewing:

Administrative data

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:
other: see 'Remark'
Remarks:
Read-across to tetradonium bromide from data on cetrimonium chloride (with data reliability value of 2).

Data source

Reference
Reference Type:
other: Assessment report for American Chemistry Council, Fatty Nitrogen Derivatives Panel, Cationics Task Group
Title:
Unnamed
Year:
2001

Materials and methods

Principles of method if other than guideline:
No guideline stated
GLP compliance:
not specified
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
The SCCS opinion document and the assessment report for American Chemistry Council, Fatty Nitrogen Derivatives Panel, Cationics Task Group refer to a study with cetrimonium chloride.
- Name of test material (as cited in study report): cetrimonium chloride
- Molecular formula (if other than submission substance): C19H42N.Cl
- Molecular weight (if other than submission substance): 320.0
Specific details on test material used for the study:
1-Hexadecanaminium, N,N,N-trimethyl-, chloride (CAS RN 112-02-7; Ammonium, hexadecyltrimethyl-, chloride)

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Three males and three females weighed between 2.25 and 2.90 kg at study initiation. Prior to dosing, the fur was clipped from the test site (approximately 25% of the total body surface). The skin at the application site of one male and two female rabbits was abraded. The skin of the remaining rabbits was not abraded. The undiluted test substance was applied once dermally to the prepared site at the dose level of 4.3 ml/kg. The test substance was spread over the clipped area with a glass stirring rod. The entire test site was covered with two layers of 8-ply gauze, occluded with rubber dental dam and secured with porous tape. The rabbits were restrained in Newmann harnesses and returned to their cages for 24 hours.
Duration of exposure:
24 hours
Doses:
4.3 ml/kg
No. of animals per sex per dose:
3
Details on study design:
After the 24-hour exposure period, the harnesses were removed, the occlusive wraps were removed and any remaining test substance was wiped off with a wet disposable towel. Test sites were graded for signs of irritation. Each rabbit was examined thoroughly for signs of systemic toxicity, changes in behavior, mortality and dermal irritation for 14 consecutive days following the day of dosing. After the 14-day observation period, the surviving animals were weighed, killed and necropsied to observe any internal gross effects. A gross necropsy was performed on each animal that died.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
4.3 mL/kg bw
Based on:
test mat.
Mortality:
One female rabbit died on day 5, one male died on Day 8 and one male died on day 13.
Clinical signs:
Signs of skin irritation noted at the end of the 24-hour exposure period included slight to severe erythema, moderate or severe edema and whitening
of the skin of the exposure area. The erythema remained relatively unchanged throughout the study while the edema subsided slightly. Also, moderate or severe atonia was noted on day 3 through termination or until death, moderate or marked coriaceous skin from day 2 through termination or death and fissuring in three rabbits and desquamation in one animal.
Body weight:
All rabbits showed a substantial weight loss during the study.
Gross pathology:
At the end of the 24-hour exposure period, all animals exhibited normal behavior and appearance. On day 3, all rabbits exhibited depressed reflexes, body cold to touch, eating and defecating very little or none at all, a clear fluid around the nose and mouth, chin and front limbs. One male and one female rabbit held their heads in a downward and tilted position and the nictitating membranes and eyelid were reddened. These signs persisted throughout the major portion of the study or until death occurred.
Necropsy findings in the animals that died included brown, liquid, fecal material around the anal area, back legs and in colon, lungs adhered to chest wall, lungs white and filled with white granular pockets, gall bladder enlarged and brownish or clear fluid around nose, mouth, chin and front limbs. No visible lesions were noted during the necropsies of the surviving animals at termination.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The only dosage tested (4.3 ml/kg bw) caused death in 50% of the animals, and therefore 4.3 ml/kg bw (comparable to 2150 mg/kg bw with a density of 0.5 g/ml)is considered the LD50-value of cetrimonium chloride. Thus no classifcation for acute dermal toxicity applies according to the CLP critera.
Executive summary:

The study reported in the SCCS opinion document and in the assessment report for American Chemistry Council, Fatty Nitrogen Derivatives Panel, Cationics Task Group describes an acute dermal toxicity test with cetrimonium chloride in 6 New Zealand white albino rabbits. The application site (approximately 25% of the total body surface) was clipped and for three animals the skin was abraded. The test substance was applied once dermally to the prepared site at the dose level of 4.3 ml/kg. The entire test site was occluded. After 24 hours of exposure, a 14 -day observation period followed. The only dosage tested (4.3 ml/kg bw) caused death in 50% of the animals, and therefore 4.3 ml/kg bw (comparable to 2150 mg/kg bw with a density of 0.5 g/ml) is considered the LD50-value of cetrimonium chloride. Thus no classifcation for acute dermal toxicity applies according to the CLP critera.