Cetrimonium bromide

Toxicity to reproduction

Administrative data

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Study initiated October 2019, Dose Range Finding (DRF) Study October 2019, Necropsy November 2019.

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2021

Report date:

2021

Materials and methods

Principles of method if other than guideline:

DRF study for “Combined 28-day repeated dose toxicity study with the reproduction/developmental toxicity screening of FeF cetyl trimethyl ammonium bromide (CTAB) USP/NF by oral gavage in rats” to follow OECD Guideline 422. Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test, July 2016 and EPA Health Effects Test Guideline OPPTS 870.3650: Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test, July 2000

GLP compliance:

yes

Remarks:

DRF study perfomed according to GLP,. Reported in Appendix 6, Appendix 7 and Appendix 8 of the report on main study 20212915

Test material

Test material information

Constituent 1

Reference substance name:

Cetrimonium bromide

EC Number:

200-311-3

EC Name:

Cetrimonium bromide

Cas Number:

57-09-0

Molecular formula:

C19H42N.Br

IUPAC Name:

cetrimonium bromide

Test material form:

solid

Specific details on test material used for the study:

White powder
Batch (Lot) Number: GX0B433
Expiry date: 31 December 2022
Purity: 100% according to certificate of analysis

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

Dose levels: 0, 50, 100, 200, 300 mg/kg bw/day

Duration of treatment / exposure:

14 days

Frequency of treatment:

daily

No. of animals per sex per dose:

3 female rats/ group

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

All rats treated at 100, 200 and 300 mg/kg/day were sacrificed moribund at Day 5, 4 and 3 respectively. Cause of moribundity were considered test item-related forestomach lesions in all rats in the form of the macroscopic finding irregular surface with the microscopic correlate ulceration/erosion of the forestomach up to marked degree. This was accompanied by (sub) mucosal edema (up to moderate) and lymphogranulocytic inflammation (up to marked) and/or squamous cell hyperplasia (minimal).
Furthermore, findings in the glandular stomach were noted which consisted of a focal ulcer at 300 mg/kg/day (minimal) and from 200 mg/kg/day onward a slightly increased incidence of granulocytic infiltrate (minimal). Although these findings can be seen as spontaneous background findings, a relationship with treatment with the test item for these latter two findings cannot be excluded.
Minor findings were noted for the intestines which included a minor increase in incidence and/or severity of inflammatory cell infiltrate (up to slight) at 200 and/or 300 mg/kg/day and epithelial necrosis in the duodenum of one rat treated at 300 mg/kg/day (minimal). A test item-relationship cannot be excluded.
There was no microscopic correlate for the macroscopic finding gelatinous contents (considered test item-related) noted in the stomach of all 300 mg/kg/day treated rats and in the intestinal tract of all rats treated at 100, 200 and 300 mg/kg/day.
There were no test item-related morphologic alterations in rats treated at 50 mg/kg/day for 14 consecutive days.

Dermal irritation (if dermal study):

not specified

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

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

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Effect levels (P0)

1

Key result

Dose descriptor:

NOAEL

Effect level:

ca. 50 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

female

Basis for effect level:

gross pathology

2

Key result

Dose descriptor:

LOAEL

Effect level:

ca. 100 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

female

Basis for effect level:

gross pathology

Results: F1 generation

Effect levels (F1)

Remarks on result:

not determinable because of methodological limitations

Overall reproductive toxicity

Reproductive effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Adverse test item-related morphologic alterations following the administration of FeF Cetyl Trimethyl Ammonium Bromide (CTAB) USP/NF were noted at 100, 200 and 300 mg/kg/day in the form of an early onset of moribundity related with marked forestomach ulceration/erosion and concomitant findings, as edema, inflammation and squamous cell hyperplasia.

Treatment for 14 days at 50 mg/kg/day was well tolerated.
Due to the observed steep dose-reponse relationship for forestomach ulceration/erosion and because of longer exposure period in the main study, the maximum dose in the main study should be no higher than 50 mg/kg bw/day.