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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
February - August 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
(2-hydroxy-3-sulphopropyl)dimethyl[3-[(1-oxooctyl)amino]propyl]ammonium hydroxide
Molecular formula:
C16H34N2O5S
IUPAC Name:
(2-hydroxy-3-sulphopropyl)dimethyl[3-[(1-oxooctyl)amino]propyl]ammonium hydroxide
Constituent 2
Chemical structure
Reference substance name:
(2-hydroxy-3-sulphopropyl)dimethyl[3-[(1-oxodecyl)amino]propyl]ammonium hydroxide
Molecular formula:
C18H38N2O5S
IUPAC Name:
(2-hydroxy-3-sulphopropyl)dimethyl[3-[(1-oxodecyl)amino]propyl]ammonium hydroxide
Constituent 3
Chemical structure
Reference substance name:
(2-hydroxy-3-sulphopropyl)dimethyl[3-[(1-oxododecyl)amino]propyl]ammonium hydroxide
EC Number:
242-893-1
EC Name:
(2-hydroxy-3-sulphopropyl)dimethyl[3-[(1-oxododecyl)amino]propyl]ammonium hydroxide
Cas Number:
19223-55-3
Molecular formula:
C20H42N2O5S
IUPAC Name:
N-[3-(dodecanoylamino)propyl]-2-hydroxy-N,N-dimethyl-3-sulfopropan-1-aminium hydroxide
Constituent 4
Chemical structure
Reference substance name:
(2-hydroxy-3-sulphopropyl)dimethyl[3-[(1-oxotetradecyl)amino]propyl]ammonium hydroxide
Molecular formula:
C22H46N2O5S
IUPAC Name:
(2-hydroxy-3-sulphopropyl)dimethyl[3-[(1-oxotetradecyl)amino]propyl]ammonium hydroxide
Constituent 5
Chemical structure
Reference substance name:
(2-hydroxy-3-sulphopropyl)dimethyl[3-[(1-oxohexadecyl)amino]propyl]ammonium hydroxide
Molecular formula:
C24H50N2O5S
IUPAC Name:
(2-hydroxy-3-sulphopropyl)dimethyl[3-[(1-oxohexadecyl)amino]propyl]ammonium hydroxide
Constituent 6
Chemical structure
Reference substance name:
[2-hydroxy-3-sulphopropyl]dimethyl[3-[(1-oxooctadecyl)amino]propyl]ammonium hydroxide
EC Number:
264-390-6
EC Name:
[2-hydroxy-3-sulphopropyl]dimethyl[3-[(1-oxooctadecyl)amino]propyl]ammonium hydroxide
Cas Number:
63663-12-7
Molecular formula:
C26H54N2O5S
IUPAC Name:
2-hydroxy-N,N-dimethyl-N-[3-(stearoylamino)propyl]-3-sulfopropan-1-aminium hydroxide
Constituent 7
Chemical structure
Reference substance name:
Water
EC Number:
231-791-2
EC Name:
Water
Cas Number:
7732-18-5
Molecular formula:
H2O
IUPAC Name:
Water
impurity 1
Chemical structure
Reference substance name:
Sodium chloride
EC Number:
231-598-3
EC Name:
Sodium chloride
Cas Number:
7647-14-5
Molecular formula:
ClNa
IUPAC Name:
sodium chloride
impurity 2
Chemical structure
Reference substance name:
Glycerol
EC Number:
200-289-5
EC Name:
Glycerol
Cas Number:
56-81-5
Molecular formula:
C3H8O3
IUPAC Name:
glycerol
impurity 3
Chemical structure
Reference substance name:
Disodium 2-hydroxypropane-1,3-disulfonate
Molecular formula:
C3H8O7S2.Na2
IUPAC Name:
Disodium 2-hydroxypropane-1,3-disulfonate
impurity 4
Chemical structure
Reference substance name:
Sodium (±)-2,3-dihydroxypropanesulphonate
EC Number:
252-542-4
EC Name:
Sodium (±)-2,3-dihydroxypropanesulphonate
Cas Number:
35396-47-5
Molecular formula:
C3H8O5S.Na
IUPAC Name:
sodium (±)-2,3-dihydroxypropanesulphonate
impurity 5
Chemical structure
Reference substance name:
Amides, C8-18 even numbered, N-[3-(dimethylamino)propyl]
EC Number:
930-947-3
IUPAC Name:
Amides, C8-18 even numbered, N-[3-(dimethylamino)propyl]
Test material form:
liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: approx. 8 weeks old
- Weight at study initiation: 320-348 g (males) - 214-248 g (females)
- Fasting period before study: No
- Housing: By 5 from the same sex and group in polycarbonate cages with stainless steel lids containing autoclaved sawdust, with nylabone used as enrichment
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 8 days (males) - 5 days (females) before application

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 50 +/- 20
- Air changes (per hr): 12 cycles
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 05 March 2012 To: 23 March 2012

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: approx. 7 x 5 cm for males, 6 x 5 cm for females
- % coverage: approx. 10% of total body surface
- Type of wrap if used: Application site covered with aerated hypoallergic dressing

REMOVAL OF TEST SUBSTANCE
No washing

TEST MATERIAL
- Solution applied as is.
- Quantity of test item applied adjusted based on the body weight recorded on the day of application.
- Correction factor of 2.76 used to calculate the dosage volume to be applied taking account of the solution purity.
Duration of exposure:
24 hours
Doses:
2000 mg active ingredient/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
. Morbidity / mortality: frequently during hours following application, at least once daily for the remainder of the observation period
. Clinical signs: at least once during first 30 minutes, periodically during first 4 hours, once daily for the remainder of the observation period
. Bodyweight: recorded on the day of group allocation, then on the day of application (day 1) and on days 8 and 15
- Necropsy of survivors performed: yes (spleen was preserved in 10% buffered formalin, stored, and destroyed at finalization of study report)
Statistics:
No statistical analyses included

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
act. ingr.
Mortality:
No unscheduled deaths observed
Clinical signs:
No clinical signs indicative of systemic toxicity observed.
Very slight or well defined erythema noted at application site for 2 females on day 2.
Body weight:
Mean bodyweight gain was slightly lower than historical control data for females over the observation period, notably during the first week. However, no such changes were observed for males.
Gross pathology:
Enlargement of the spleen was found in all treated animals but was considered incidental as it is part of the normal background in untreated rats of these strain and age.
Other findings:
Due to enlargement seen at necropsy, spleens were preserved in 10% buffered formalin and stored. In the absence of toxicological relevance, no histopathology was conducted and these organs were therefore destroyed upon finalization of the study report.

Any other information on results incl. tables

 

Females

Males

Historical controls

Treated

Historical controls

Treated

Dose level (mg/kg)

0

2000

0

2000

Days 1-8

+36

+21

+45

+41

Days 8-15

+18

+16

+45

+44

Days 1-15

+55

+37

+90

+84

 

Mean bodyweight gains (grams) during the observation period

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The dermal LD50 in rats was higher than 2000 mg active ingredient/kg bw.
Executive summary:

Cocamidopropyl hydroxysultaine, as a 36.2% solution (Mackam CBS-50GE), has been tested for acute dermal toxicity in Sprague-Dawley rats. The test article was applied as a single dose under a semi-occlusive dressing for 24 hours. One group of 5 rats per sex received a dose of 2000 mg active ingredient/kg bw. Examinations for mortality and clinical signs were performed daily during the 14 -day study period. Animals were necropsied at the end of the observation period.

 

No mortality was observed. No clinical signs indicative of systemic toxicity were observed. Very slight or well defined erythema was noted at the application site for 2 females on day 2. Mean bodyweight gain was slightly lower than historical control data for females over the observation period, notably during the first week following application. However, no such changes were observed for males. Enlargement of the spleen was found in all treated animals but was considered incidental as it is part of the normal background in untreated rats of these strain and age.

The dermal LD50 in rats was therefore higher than 2000 mg active ingredient/kg bw.