Registration Dossier

Registration Dossier

Diss Factsheets

Toxicological information

Skin irritation / corrosion

Currently viewing:

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
September 15th, 1987 to September 29th, 1987
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Read across justification is presented from the structurally analogous quaternary ammonium compounds, di-C12-18-alkyldimethyl, chlorides to the quaternary ammonium compounds, di-C12-18-alkyldimethyl, nitrites.

In 1988, the US EPA, Office of Pesticides and Toxic Substances issued a Notice to producers, Formulators, Distributors and Registrants regarding quaternary ammonium compounds with regard to "Clustering" of such quaternary ammonium compounds.

Prior to this, EPA had required each quat compound to be individually coded and registered as a new chemical, even when the chemical structure of individual compounds differed only slightly in alkyl distribution and chain lengths. This procedure was continued with the new generations of quats having two, three, and four chains. As a result, EPA records showed that some 211 registered technical grade active ingredient products containing varying concentrations of Quats, each coded separately on the basis of alkyl chain length and percentage carbon distribution within the chain. At this time, there are approximately eight to ten thousands (8-10,000) registered end-use formulations.

However, questions were raised regarding whether the EPA could cluster or group the quats and pick one or more representative members of each cluster to be used in toxicity studies, instead of requiring separate studies on each quat. These same questions were raised when the EPA issued its March 4, 1987 Data Call-In Notice requiring all registrants of antimicrobial active ingredients to submit subchronic and chronic toxicological data to support the continued registration of their products.

In response to these questions, EPA·solicited information from industry, the public, academia, industry cooperative work groups, the state of California, and Canada. EPA then reviewed all of the assembled information along with the chemical structure of most of the quats. Based on the results of this review, EPA developed the following four groupings of currently registered quat compounds:

Group I. The alkyl or hydroxyalkyl (straight chain) substituted Quats
Group II. The non-halogenated benzyl substituted Quats (includes hydroxybenzyl, ethylbenzyl, hydroxyethybenzyl, napthylmethyl, dodecylbenzyl, and alkyl benzyl)
Group III. The di-and tri-chlorobenzyl substituted
Group IV. Quats with unusual substituents (charged heterocyclic ammonium compounds).

Fundamental to this discussion EPA determined that "X-" in all of these structures would be attributed to "any anionic species". Therefore, this would mean in terms of toxicological evaluation the coutner anion in such quaternary ammonium compounds could be regarded as; e.g halogen (Cl-, Br-, I-,), saccharinate or cyclohexylsulphamate. It is therefore suggested here that nitrite (NO2-) could also be regarded as a pertinent anion.

Since the US EPA deem that such a clustering of structures for toxicological evaluation is well founded then it would seem that to consider read-across data from quaternary ammonium compounds, di-C12-18-alkyldimethyl, chlorides to the closely structurally analogous quaternary ammonium compounds, di-C12-18-alkyldimethyl, nitrites to be equally justifiable.

Furthermore, in certain organic solvents it has been reported that the exchange constants between nitrite and chloride in quaternary ammonium salts (QAS) are approximately equal. [Zhurnal Analiticheskoi Khimii, 2010, Vol. 65, No. 6, pp. 579–584. (E.M. Rakhman’ko, M.S. Markovskaya, L.S. Stanishevskii, Yu.S. Zubenko, A.R. Tsyganov)]

Cross-reference
Reason / purpose for cross-reference:
read-across: supporting information
Reference
Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
not specified
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
Didecyldimethylammonium chloride
EC Number:
230-525-2
EC Name:
Didecyldimethylammonium chloride
Cas Number:
7173-51-5
Molecular formula:
C22H48N.Cl
IUPAC Name:
Didecyldimethylammonium chloride
Test material form:
liquid
Specific details on test material used for the study:
- Name of test material (as cited in study report): Querton 210-CL-80
- Composition of test material, percentage of components: ca. 80% Didecyldimethylammonium chloride (DDAC) (CAS no.: 7173-51-5), 15% isopropanol (IPA) (CASno.: 67-63-0), remaining water

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Nottingham University, School of Agriculture, Sutton Bonington, Leicestershire, U.K.
- Age at study initiation: 12-16 wk
- Weight at study initiation: 2.19 - 2.42 kg

Test system

Type of coverage:
occlusive
Preparation of test site:
other: closely clipping the fur from the dorsal/flank areas using veterinary clippers
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
Undiluted
Duration of treatment / exposure:
Up to 60 minutes
Observation period:
The skin was assessed immediately after removal of the patch and again at 24, 48 and 72 h, and at 7 and 14 d
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: Clipped dorsal flanks
- Type of wrap if used: Occlusive patches
- 0.5 mL of test material was applied under occlusive patches on the clipped dorsal flanks of three rabbits and left for 3 min application on one flank and 60 min application on the other flank.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Gentle swabbing with cotton wool soaked in 3 % (v/v) aqueous acetic acid followed by cotton wool soaked in distilled water.

EVALUATION:
Approximately 1 h following removal of the patches and 24, 48 and 72 h and 7 and 14 d later, the test sites (a total of six) were examined for evidence of primary irritation and scored according to Draize (1959).

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
24 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Eschar, moderate erythema extending beyond site, blanching of skin, scattered punctate formation
Irritation parameter:
erythema score
Basis:
mean
Time point:
48 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Eschar, moderate erythema extending beyond site, blanching of skin, scattered punctate formation
Irritation parameter:
erythema score
Basis:
mean
Time point:
72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Eschar, moderate erythema extending beyond site, blanching of skin, scattered punctate formation
Irritation parameter:
edema score
Basis:
mean
Time point:
24 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Oedema extending beyond site
Irritation parameter:
edema score
Basis:
mean
Time point:
48 h
Score:
3.6
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Oedema extending beyond site
Irritation parameter:
edema score
Basis:
mean
Time point:
72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Oedema extending beyond site

Any other information on results incl. tables

After three minutes exposure:

No adverse skin reaction were noted at any treated skin site 1 h after the removal of the patches. Very slight or well-defined erythema had developed at two treated skin sites at the 24 h observation and continued to be noted at  all  the  treated  sites  at the  48  and 72 h  observations. Very slight oedema was noted at one treated site at the 24 and 48 h observations and at two treated sites at the 72 h observation. 


After one hour exposure:
A light brown discoloration of the epidermis and slight haemorrhage of the dermal capillaries were noted at all treated  skin  sites 1 h  after  the  removal of the patches. Blanching of the skin was also noted at two of the skin sites. Eschar had developed at all treated skin sites at the 24 h observation and continued to be noted at the 48, 72 h and Day 7 observation. Blanching and moderate  erythema  extending  up to  approximately 7 cm beyond the treatment site were also noted at all the treated skin sites during this period. Scattered punctate eschar
surrounding two of the skin sites was also noted, with dry, straw-coloured skin evident at all the sites on Day 7. On Day 14  sunken  eschar  was  noted at all the treated skin sites. Severe oedema was noted at all the treated sites 1h after the removal of the patches. The oedema gradually decreased and appeared as very slight to slight on Day 7.  The oedema extended approximately 2 to 3 cm beyond all treated skin sites during this period. No oedema was noted on Day 14.

Applicant's summary and conclusion

Interpretation of results:
Category 1B (corrosive) based on GHS criteria
Conclusions:
The test material (containing 80% didecyldimethylammonium chloride) was considered to be corrosive to skin in rabbits and can be classified as Category 1B corrosive according to CLP Regulation (EC 1272/2008).
Executive summary:

An OECD guideline 404 study was conducted to evaluatethe skin irritation potential of the test material (containing 80% didecyldimethylammonium chloride -DDAC, 15% isopropanol and 5% water) in rabbits.

The study was assigned a reliability score of 1 in accordance with the criteria for assessing data quality set forth by Klimisch et al. (1997).

Study was0.5 mL samples were applied under occlusive patches for both 3 and 60 min on the clipped skin of 3 rabbits. Residual test material was removed using cotton wool soaked in 3% (v/v) aqueous acetic acid followed by distilled water. The skin was assessed immediately after removal of the patch and again at 24, 48 and 72 h, and at 7 and 14 d.After 3 min exposure, very slight or well-defined erythema had developed at two treated skin sites at the 24 h observation and continued to be noted at all the treated sites at the 48 and 72 h observations. Very slight oedema was noted at one treated site at the 24 ad 48 h observations and at two treated sites at the 72 h observation. On Day 7 and 14, some hyperkeratinisation (2/3) and desquamation (1/3) was still present.After 1 h exposure, a light brown discolouration of the epidermis and slight haemorrhage of the dermal capillaries were noted at all treated skin sites 1 h after the removal of the patches. Blanching of the skin was also noted at two of the skin sites. Eschar had developed at all treated skin sites at the 24 h observation and continued to be noted at the 48, 72 h and Day 7 observations. Blanching and moderate erythema extending up to approximately 7 cm beyond the treatment site were also noted at all the treated skin sites during this period. Scattered punctuate eschar surrounding two of the skin sites was also noted, with dry, straw-coloured skin evident at all the sites on Day 7.On Day 14 sunken eschar was noted at all the treated skin sites. Severe oedema was noted at all the treated sites 1 h after the removal of the patches. The oedema gradually decreased and appeared as very slight to slight on Day 7. The oedema extended approximately 2 to 3 cm beyond all treated skin sites during this period. No oedema was noted on Day 14.

Under the test conditions, the test material (containing 80% DDAC) was found to be corrosive to skin in rabbits and can be classified as Category 1B corrosive according to CLP Regulation (EC 1272/2008).

Categories Display

EU Privacy Disclaimer

This website uses cookies to ensure you get the best experience on our websites.