Registration Dossier

Administrative data

Description of key information

Other than slight clinical chemistry changes observed in high dose animals; no gross or histologic alterations, including to reproductive organs, attributed to test material (cetyl betaine) were observed. In addition, reviews by US EPA on the class of substance (surrogate betaines) demonstrate that toxicity for this class is limited to GI tract irritation with no evidence of specific organ toxicity.

In view of the primary use in cosmetics, further animal testing can not be justifed.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Referenceopen allclose all

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
91 days
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents)
Deviations:
not specified
GLP compliance:
yes
Specific details on test material used for the study:
cetyl betaine tested at 32% active adjusted to be delivered at doses of 0, 0.05, 0.15, 0.35 g/kg/day
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Dose / conc.:
0 mg/kg bw/day (nominal)
Dose / conc.:
50 mg/kg bw/day (nominal)
Dose / conc.:
150 mg/kg bw/day (nominal)
Dose / conc.:
350 mg/kg bw/day (nominal)
No. of animals per sex per dose:
10
Clinical signs:
no effects observed
Description (incidence and severity):
All animals survived until end of treatment period; no treatment-related clinical observations; mean body weights and body weight gains significantly decreased in high dose males which was accompanied by significantly decreased total feed consumption – these observations were attributed to palatability problems of diet than toxic effects of test material; slight clinical chemistry changes observed in high dose animals; no gross or histologic alterations, including to reproductive organs, attributed to test material observed
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, non-treatment-related
Description (incidence and severity):
attributed to palatability problems of diet
Gross pathological findings:
no effects observed
Dose descriptor:
NOAEL
Effect level:
350 mg/kg bw/day (nominal)
Based on:
act. ingr.
Sex:
not specified
Basis for effect level:
clinical signs
Critical effects observed:
no

Other than slight clinical chemistry changes observed in high dose animals; no gross or histologic alterations, including to reproductive organs, attributed to test material were observed

Conclusions:
Although the details in the CIR review are brief and the primary data source is unpublished (Hazleton Laboratories America Inc. 1990. 91-Day subchronic oral toxicity study in rats with Cetyl Betaine. Unpublished data submitted by Personal Care Products Council. 74 pages), the CIR panel consider the result valid.
There appears to be no specifc target organ
Endpoint:
short-term repeated dose toxicity: oral
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Justification for type of information:
Other than slight clinical chemistry changes observed in high dose animals; no gross or histologic alterations, including to reproductive organs, attributed to test material (cetyl betaine) were observed. In addition, reviews by US EPA on the class of substance (surrogate betaines) demonstrate that toxicity for this class is limited to GI tract irritation with no evidence of specific organ toxicity.
In view of the primary use in cosmetics, further animal testing can not be justifed.
Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
28 days
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Information taken from US EPA review of surrogate substance
Considered reliable by EPA, although primary source not known.
Because of the structural and functional similarities and comparable physico-chemical properties these inner salts and sodium salts, a similar ecotoxicological and toxicological profile can be expected between this test material and cetyl betaine.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
GLP compliance:
not specified
Remarks:
Assumed GLP - EPA considers valid study
Specific details on test material used for the study:
The test material is a betaine
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
water
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
28 days
Frequency of treatment:
Daily
Dose / conc.:
0 mg/kg bw/day (nominal)
Dose / conc.:
250 mg/kg bw/day (nominal)
Dose / conc.:
500 mg/kg bw/day (nominal)
Dose / conc.:
1 000 mg/kg bw/day (nominal)
Control animals:
yes, concurrent vehicle
Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Salivation
Mortality:
no mortality observed
Body weight and weight changes:
not specified
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
Signs of irritation to GI rtract in highest dose
Dose descriptor:
NOAEL
Effect level:
500 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
gross pathology
Critical effects observed:
no

Other than local effects to GI tract in thehighest dose levels, no other adverse effects were reported in the review document.

Conclusions:
Although the EPA review is brief and the primary data source is unknown, the EPA consider the result valid.
There appears to be no specifc target organ
Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
90 days
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Information taken from US EPA review of surrogate substance
Considered reliable by EPA, although primary source not known.
Because of the structural and functional similarities and comparable physico-chemical properties these inner salts and sodium salts, a similar ecotoxicological and toxicological profile can be expected between this test material and cetyl betaine.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents)
GLP compliance:
not specified
Remarks:
Assumed GLP - EPA considers valid study
Specific details on test material used for the study:
The test material is a betaine. Because of the structural and functional similarities and comparable physico-chemical properties these inner salts and sodium salts, a similar ecotoxicological and toxicological profile can be expected between this test material and cetyl betaine.
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
water
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
90 days
Frequency of treatment:
Daily
Dose / conc.:
0 mg/kg bw/day (nominal)
Dose / conc.:
250 mg/kg bw/day (nominal)
Dose / conc.:
500 mg/kg bw/day (nominal)
Dose / conc.:
1 000 mg/kg bw/day (nominal)
No. of animals per sex per dose:
ten
Control animals:
yes, concurrent vehicle
Observations and examinations performed and frequency:
Daily
Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Salivation
Mortality:
no mortality observed
Body weight and weight changes:
not specified
Ophthalmological findings:
no effects observed
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
Signs of irritation to GI rtract in highest dose
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Dose descriptor:
NOAEL
Effect level:
250 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
gross pathology
Critical effects observed:
no

Other than local effects to GI tract in the highest dose levels, no other adverse effects were reported in the review document.

Conclusions:
Although the EPA review is brief and the primary data source is unknown, the EPA consider the result valid.
There appears to be no specifc target organ
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Justification for classification or non-classification