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Administrative data

Description of key information

NOAEL was considered to be 500 mg/kg bw when male and female Sprague-Dawley rats were treated with cocamidopropyl betaine orally by gavage for 28 days.

Hence the test chemical is not likely to classify as repeated dose oral toxic as per the criteria mentioned in CLP regulation

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Justification for type of information:
Data is from secondary source
Qualifier:
according to
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
Principles of method if other than guideline:
28 days repeated dose oral toxicity study of cocamidopropyl betaine in rats.
GLP compliance:
not specified
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
not specified
Route of administration:
oral: gavage
Details on route of administration:
not specified
Vehicle:
water
Remarks:
distilled
Details on oral exposure:
not specified
Analytical verification of doses or concentrations:
not specified
Details on 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 (actual dose received)
Dose / conc.:
250 mg/kg bw/day (actual dose received)
Dose / conc.:
500 mg/kg bw/day (actual dose received)
Dose / conc.:
1 000 mg/kg bw/day (actual dose received)
No. of animals per sex per dose:
Total: 1000 mg/kg day: 10 male, 10 female 250 mg/kg day: 10 male, 10 female500 mg/kg day: 10 male, 10 female1000 mg/kg day: 10 male, 10 femaleRecovery groups0 mg/kg day: 5 male, 5 female 1000 mg/kg day: 5 male, 5 female
Control animals:
yes, concurrent vehicle
Details on study design:
not specified
Positive control:
not specified
Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes - Time schedule:- Cage side observations checked in table [No.?] were included. Mortality were observed DETAILED CLINICAL OBSERVATIONS: Yes - Time schedule:BODY WEIGHT: No data- Time schedule for examinations:FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes / No / No data- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No dataFOOD EFFICIENCY:- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No dataWATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes / No / No data- Time schedule for examinations:OPHTHALMOSCOPIC EXAMINATION: Yes - Time schedule for examinations: No data- Dose groups that were examined: No data HAEMATOLOGY: Yes - Time schedule for collection of blood:- Anaesthetic used for blood collection: No data- Animals fasted: No data- How many animals:- Parameters checked in table [No.?] were examined. No dataCLINICAL CHEMISTRY: Yes - Time schedule for collection of blood: No data- Animals fasted: No data- How many animals: No data- Parameters checked in table [No.?] were examined. No dataURINALYSIS: No data- Time schedule for collection of urine: No data - Metabolism cages used for collection of urine: No data - Animals fasted: No data - Parameters checked in table [No.?] were examined. No data NEUROBEHAVIOURAL EXAMINATION: No data - Time schedule for examinations: No data- Dose groups that were examined: No data- Battery of functions tested: sensory activity / grip strength / motor activity / other: No dataOTHER:Absolute and relative organ weights were weighted.
Sacrifice and pathology:
GROSS PATHOLOGY: Yes HISTOPATHOLOGY: Yes
Other examinations:
not specified
Statistics:
not specified
Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
When treated with 1000 mg/kg bw, Symptoms of local irritation of the gastrointestinal tract (head protrusion at the beginning of week 3, salivation at the beginning of week 4) were observed through the end of the study.
Mortality:
no mortality observed
Description (incidence):
No effect on survival of treated rats were observed.
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:
no effects observed
Description (incidence and severity):
No effect on Opthalmoscopic examination of treated rats were observed.
Haematological findings:
no effects observed
Description (incidence and severity):
No effect on Haematology examination of treated rats were observed.
Clinical biochemistry findings:
no effects observed
Description (incidence and severity):
No effect on Clinical chemistry of treated rats were observed.
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
No effect on absolute and relative organ weights of treated rats were observed.
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
When treated with 1000 mg/kg bw, edema of the mucosa of the forestomach were observed in treated rats, which disappeared in rats of the recovery group 28 days after termination of treatment.
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
When treated with 1000 mg/kg bw, acanthosis of the mucosa, inflammatory edema of the submucosa and multiple ulcerations in treated rats. The recovery animals showed complete and regular regeneration of the forestomach mucosa.
Histopathological findings: neoplastic:
not specified
Other effects:
not specified
Dose descriptor:
NOAEL
Effect level:
500 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
mortality
ophthalmological examination
haematology
clinical biochemistry
organ weights and organ / body weight ratios
gross pathology
histopathology: non-neoplastic
Remarks on result:
other: No effect observed
Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified
Conclusions:
NOAEL was considered to be 500 mg/kg bw when male and female Sprague-Dawley rats were treated with cocamidopropyl betaine orally by gavage for 28 days.
Executive summary:

In 28 days repeated dose oral toxicity study, male and female Sprague-Dawley rats were treated with cocamidopropyl betaine in the contraction of 0, 250, 500 or 1000 mg/kg-day orally by gavage for 28 days. Symptoms of local irritation of the gastrointestinal tract (head protrusion at the beginning of week 3, salivation at the beginning of week 4) were observed through the end of the study at 1000 mg/kg bw.No effect on survival, hematological evaluations, clinical chemistry, ophthalmic examinations and absolute and relative organ weights of treated rats were observed in treated rats. In addition,edema of the mucosa of the forestomach were observed in treated rats at 1000 mg/kg bw, which disappeared in rats of the recovery group 28 days after termination of treatment. Acanthosis of the mucosa, inflammatory edema of the submucosa and multiple ulcerations in treated rats at 1000 mg/kg bw. The recovery animals showed complete and regular regeneration of the forestomach mucosa. Therefore, NOAEL was considered to be 500 mg/kg bw when male and female Sprague-Dawley rats were treated with cocamidopropyl betaine orally by gavage for 28 days.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
500 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
Data is Klimisch 4 and from secondary source

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records
Reference
Endpoint:
repeated dose toxicity: inhalation, other
Data waiving:
other justification
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records
Reference
Endpoint:
repeated dose toxicity: dermal, other
Data waiving:
other justification
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Repeated dose oral toxicity:

Data available for target and the read across chemicals was reviewed to determine the repeated dose oral toxicity of 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., inner salts (CAS no 61789-40-0). The studies are as mentioned below:

Study 1:

In 28 days repeated dose oral toxicity study, male and female Sprague-Dawley rats were treated with cocamidopropyl betaine in the contraction of 0, 250, 500 or 1000 mg/kg-day orally by gavage for 28 days. Symptoms of local irritation of the gastrointestinal tract (head protrusion at the beginning of week 3, salivation at the beginning of week 4) were observed through the end of the study at 1000 mg/kg bw.No effect on survival, hematological evaluations, clinical chemistry, ophthalmic examinations and absolute and relative organ weights of treated rats were observed in treated rats. In addition,edema of the mucosa of the forestomach were observed in treated rats at 1000 mg/kg bw, which disappeared in rats of the recovery group 28 days after termination of treatment. Acanthosis of the mucosa, inflammatory edema of the submucosa and multiple ulcerations in treated rats at 1000 mg/kg bw. The recovery animals showed complete and regular regeneration of the forestomach mucosa. Therefore, NOAEL was considered to be 500 mg/kg bw when male and female Sprague-Dawley rats were treated with cocamidopropyl betaine orally by gavage for 28 days.

Study 2:

In 90 days repeated dose oral toxicity study, male and female Sprague-Dawley rats were treated with cocamidopropyl betaine in the contraction of 0, 250, 500 or 1000 mg/kg-day orally by gavage for 28 days. No effect on survival, clinical observations, body weight gain, food consumption, ophthalmic observations, hematologic evaluations, blood chemistry, urinalysis and organ weights were observed in treated rats. In addition, stomach ulceration at the fundus and cardiac regions and forestomach gastritis in six male and three female rats at 1000 mg/kg-day and in two males and two females at 500 mg/kg-day in treated rats. Therefore, NOAEL was considered to be 250 mg/kg bw when male and female Sprague-Dawley rats were treated with cocamidopropyl betaine orally by gavage for 90 days.     

Study 3:

In a 28 days repeated dose toxicity study, the effect of Zinc Distearate was evaluated in male and female Sprague Dawley rats. The test chemical was administered by oral gavage in the concentration of 0, 250, 500 and 1000 mg/kg/ body weight/day. The results showed no effect on mortality, no changes were in food consumption and ophthalmology. Changes were observed in clinical signs like soft stool, nasal discharge, red crustaround nostrils, perineum soiled with fecal matter. Significant decreased were observed in water consumption and locomotor activity of female rat in1000 mg/kg dose group. Bodyweight was increased significantly in male and female rats. Significant increase in MCV, Lymphocyte, Basophils level and significant decrease in WBC, platelet, monocytes, neutrophils and eosinophils were observed in male and female rats. Significant changes were observed in the level of testosterone, sodium, totalproteins, total cholesterol, SGOT, SGPT, albumin, Blood urea nitrogen (BUN) and Creatinine when treated with 500 and 1000 mg/kg/day. Significant changes were observed in absolute and relative weight of brain, adrenals, spleen, thymus, epididymides, heart, kidneys, ovaries, uterus and liver in 500 and 1000 mg/kg/day. In addition, minimal to mild gross pathological and histopathological changes were observed in liver, spleen and intestine. However, the biological significance of these findings are not related to test chemical. Therefore, NOAEL was considered to be 1000 mg/kg/day when Sprague-Dawley rat exposed to test substance orally.

Based on the data available for 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., inner salts (CAS no 61789-40-0) does not exhibit repeated dose oral toxicity. Hence the test chemical is not likely to classify as repeated dose oral toxic as per the criteria mentioned in CLP regulation

Repeated dose inhalation toxicity:

According to Annex IX of the REACH regulation, testing by the inhalation route is appropriate only if exposure of humans via inhalation is likely. Taking into account the low vapour pressure of the substance Reaction mass of 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., inner salts (CAS no 61789-40-0), which is reported as 4.60E-15 mm Hg at 25 C. Thus, exposure to inhalable dust, mist and vapour of the chemical Reaction mass of 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., inner salts is highly unlikely. Therefore this study is considered for waiver.

Repeated dose dermal toxicity:

In accordance with coloumn 2 of Annex IX, this end point was considered for waiver since the acute toxicity by the dermal route has already been provided in section 7.2.3 (as part of the Annex VIII information requirements)

Justification for classification or non-classification

Based on the data available for 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., inner salts (CAS no 61789-40-0) does not exhibit repeated dose oral, dermal and inhalation toxicity. Hence the test chemical is not likely to classify as repeated dose oral toxic as per the criteria mentioned in CLP regulation