Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read-across to cetrimonium bromide from data on cetrimonium chloride (with data reliability value of 1). Read-across justifications are provided in the endpoint summary.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Final report on the safety assessment of cetrimonium chloride, cetrimonium bromide, and steartrimonium chloride
Author:
Anonymous
Year:
1997
Bibliographic source:
International Journal of Toxicology, 16:195-220
Reference Type:
other: Assessment report for American Chemistry Council, Fatty Nitrogen Derivatives Panel, Cationics Task Group
Title:
Unnamed
Year:
2001
Reference Type:
other: SCCS opinion document
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study)
Deviations:
yes
Remarks:
only one dose level used; dosing area 25% of body surface
GLP compliance:
not specified
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: 0.5% cetrimonium chloride in water
Details on test material:
- Name of test material (as cited in study report):CETRIMONIUM CHLORIDE
- A suspension of 54.5% cetrimonium chloride was diluted with water to form a 0.5% (w/v) solution

Test animals

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

Administration / exposure

Duration of treatment / exposure:
4 weeks
Frequency of treatment:
6.5 to 7.0 h, 5 days a week
Doses / concentrations
Remarks:
Doses / Concentrations:
10 mg/kg bw/d
Basis:

No. of animals per sex per dose:
5
Control animals:
yes

Examinations

Observations and examinations performed and frequency:
observations for signs of toxicity and for mortality: twice a day
dermal irritation: scored daily
body weight: measured weekly
blood samples: taken prior to dosing and at week 4 for hematologic analyses
necropsy: either at the time of death or at the end of the study when they are killed

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Description (incidence and severity):
no death
Dermal irritation:
effects observed, treatment-related
Description (incidence and severity):
slight to moderate erythema
Mortality:
no mortality observed
Description (incidence):
no death
Body weight and weight changes:
no effects observed
Haematological findings:
no effects observed
Details on results:
Slight to moderate erythema was observed in all of the treated rabbits between days 4 and 8 but disappeared in four rabbits by day 17.
Very slight to slight edema was observed between days 6 and 12 in four rabbits and subsided by day 17.
Two rabbits had intermittent evidence of slight edema on day 20. No evidence of desquamation or coriaceousness was present in three rabbits. In the other rabbits, slight atonia was observed but persisted into week 4 in only three animals. Very slight to slight desquamation and coriaceousness was noted in most of the rabbits, but desquamation was found only in three animals and coriaceousness in two animals by week 4. Slight fissuring was observed in most of the rabbits but typically disappeared by the end of the study.
At necropsy, treatment-related changes were found only in the skin. The application sites of two rabbits were reddened, and one rabbit hadscabbing. Findings from microscopic examination included mild to marked acanthosis with active mitosis, hyperkeratosis, and partial to extensive necrosis of the epidermis and hair follicules with or without encrustation with exudate. No statistically significant changes were observed for the hepatic or renal weights between the experimental and control animals.

(The dose level of 10 mg/kg bw/d correspons to a dermal load of 0.05 mg/cm2 (assuming 25% of a body surface of 2500 cm2 (625 cm2) and a body weight of 3 kg)

Effect levels

Dose descriptor:
LOAEL
Remarks:
dermal irritation
Effect level:
10 mg/kg bw/day (nominal)
Based on:
dissolved
Sex:
male/female
Basis for effect level:
other: no systemic effects were noted

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Although some treatment related changes were observed on the skin, they were mostly reversible. No deaths occurred in the experimental group, and no evidence of toxicity or hematological changes was present at the dose of 10 mg/kg bw/day.
Executive summary:

Five New Zealand albino rabbits/sex/group were treated cutaneously with the test substance (cetrimonium chloride for 5 days/week for 4 weeks at a dose of 0 or 10 mg/kg bw/day (0 or 0.5% aqueous solutions, respectively). The dosage volume was 2.0 ml/kg bw with an approximate exposure period of 6.5 to 7 hours.

There were no treatment-related effects on body weight, haematology, organ weight, gross necropsy findings or histopathology, except for treated areas of the skin that showed mild to marked acanthosis with active mitosis, hyperkeratosis, and

partial to extensive necrosis of the epidermis and hair follicles, partly with encrustation and exudate.

(The dose level of 10 mg/kg bw/d correspons to a dermal load of 0.05 mg/cm2 (assuming 25% of a body surface of 2500 cm2 (625 cm2) and a body weight of 3 kg)