1-Propanaminium, N-(3-aminopropyl)-2-hydroxy-N,N-dimethyl-3-sulfo-, N-C12-14 acyl derivs., hydroxides, inner salts

Acute Toxicity: dermal

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 guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

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

Test material information

Constituent 1

Reference substance name:

1-Propanaminium, N-(3-aminopropyl)-2-hydroxy-N,N-dimethyl-3-sulfo-, N-(C8-18(even numbered) acyl) derivs., hydroxides, inner salts

EC Number:

939-455-3

Molecular formula:

Molecular formula, SMILES notation, InChl and Structural formula cannot be given as the substance is a UVCB.

IUPAC Name:

1-Propanaminium, N-(3-aminopropyl)-2-hydroxy-N,N-dimethyl-3-sulfo-, N-(C8-18(even numbered) acyl) derivs., hydroxides, inner salts

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:

other: No clinical signs indicative of systemic toxicity observed. Very slight or well defined erythema noted at application site for 2 females on day 2.

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

Remarks:

Migrated information Criteria used for interpretation of results: EU

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.