Didecyldimethylammonium chloride

Endpoint summary

Description of key information

Based on the results from thein vivoirritation studies, DDAC is considered to be corrosive to skin as well as eyes. 

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May 7, 1991 - May 28, 1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:Hoechst AG, Kastengrund, Conventional breed
- Age at study initiation:3-5 months
- Weight at study initiation:3.2-3.8 kg
- Housing:Separate cages
- Diet (e.g. ad libitum):Altromin 2123 rabbit maintenance diet
- Water (e.g. ad libitum):Deionised, chlorinated water
- Acclimation period:No data

ENVIRONMENTAL CONDITIONS
- Temperature (°C):18±3ºC
- Humidity (%):55±20%
- Air changes (per hr):No data
- Photoperiod (hrs dark / hrs light):12 hrs/12 hrs

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):0.5 mL
- Concentration (if solution):Neat

Duration of treatment / exposure:

3 minutes and 4 hours

Observation period:

30-60 min, 24, 48 and 72 hrs

Number of animals:

Six, three for 3-min exposure and three for 4-hr exposure

Details on study design:

TEST SITE
- Area of exposure:2.5X2.5 cm2
- Type of wrap if used:Surgical plaster covered with semi-occlusive bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done):with warm tap water
- Time after start of exposure:4 hours

SCORING SYSTEM:Draize scoring system

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 4

Max. score:

4

Reversibility:

fully reversible within: 14 days in the 3-min exposure group

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 4

Max. score:

4

Reversibility:

fully reversible within: 14 days in the 3 min exposure group

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 1 h

Score:

ca. 2

Max. score:

4

Reversibility:

fully reversible within: 14 days in the 3-min exposure group

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 1 h

Score:

ca. 1

Max. score:

4

Reversibility:

fully reversible within: 14 days in the 3-min exposure group

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 1 h

Score:

ca. 2

Max. score:

4

Reversibility:

fully reversible within: 14 days in the 3-min exposure group

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 1 h

Score:

ca. 1

Max. score:

4

Reversibility:

fully reversible within: 14 days in the 3-min exposure group

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 1 h

Score:

ca. 1

Max. score:

4

Reversibility:

fully reversible within: 14 days in the 3-min exposure group

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: 1 h

Score:

ca. 1

Max. score:

4

Reversibility:

fully reversible within: 14 days in the 3-min exposure group

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 1 h

Score:

ca. 2

Max. score:

4

Reversibility:

not reversible

Remarks:

within 72 h in the 4 h exposure group

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 1 h

Score:

ca. 3

Max. score:

4

Reversibility:

not reversible

Remarks:

within 72 h in the 4 h exposure group

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 1 h

Score:

ca. 4

Max. score:

4

Reversibility:

not reversible

Remarks:

within 72 h in the 4 h exposure group

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 1 h

Score:

ca. 4

Max. score:

4

Reversibility:

not reversible

Remarks:

within 72 h in the 4 h exposure group

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 1 h

Score:

ca. 4

Max. score:

4

Reversibility:

not reversible

Remarks:

within 72 h in the 4 h exposure group

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: 1 h

Score:

ca. 4

Max. score:

4

Reversibility:

not reversible

Remarks:

within 72 h in the 4 h exposure group

Irritant / corrosive response data:

Exposure to the test substance for 4 hours resulted in well-defined to severe erythema as well as very severe edema from 30 minutes upto 72 hours after removal of patches. Additionally, the skin surfaces was largely discolored, dry, rough and scabbed.

Exposure to the test substance for 3 min resulted very slight edema and from 30 min to 72 hours after removal of the patches. Additionally very slight to severe erythema were observed upto 7 days. Additionally, the skin surfaces was largely discolored, dry, rough and leather-like.

Other effects:

None

All animals in the 4 hour exposure group were sacrificed after the 72 hour observation period.                     

Conclusions:

Based on the study results, the test substance is considered to be corrosive to skin.

Executive summary:

A study was carried out in rabbits to determine the primary dermal irritation of the test substance according to OECD guideline and EU method, under GLP conditions. Dorsal hair is removed by clipping in 6 animals and the neat test substance was applied to the clipped skin under a semi-occlusive bandage. The animals were divided into two groups according to the exposure period - 3 -minute and 4 -hours exposure groups. After removal of the patches, the skin is observed for signs of irritation. In this study, the 4 h exposure produced severe erythema and severe edema up to the 72 h observation period and the skin appeared rough, dry, scabbed with discoloration. The 3 minute exposure produced slight erythema, slight to severe edema up to 7 days and at end of 14 day observation period, the skin appeared dry, rough and leather-like. The mean score for edema and erythema was 4 up to the observation period of 72 h. Based on the study results, the test substance was found to be corrosive to skin.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

15 Sep, 1987 - 29 Sep, 1987

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Species Rabbit
Strain New Zealand White
Source Nottingham University, School of Agriculture, Sutton Bonington, Leicestershire, U.K.
Sex Not specified
Age/weight at study initiation: 12-16 weeks, 2.19 - 2.42 kg
Number of animals per group: 3 animals tested
Control animals: No
Temperature: 14-21ºC
Humidity:60-72%
Air exchange rate: 15 per hour
Light/dark cycle: 12 hrs/12 hrs

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:

0.5 mL of the undiluted test material

Duration of treatment / exposure:

3 min and 60 min

Observation period:

The skin was assessed 1 hour after removal of the patch and again after 24, 48 and 72 hours. The animals were continued to be observed for reversibility of signs on Day 7 and 14.

Number of animals:

3 animals per group

Details on study design:

0.5 mL of test material was applied under occlusive patches on the clipped dorsal area of a total of six rabbits per group. The animals were left for an exposure period of 3 min for three animals and 1 hour for the other three animals. Residual test material was removed by gentle swabbing with cotton wool soaked in 3% (v/v) aqueous acetic acid followed by cotton wool soaked in distilled water. Approximately one hour following removal of the patches, and 24, 48 and 72 hours and 7 and 14 days later, the test sites were examined for evidence of primary irritation and scored according to Draize (1959).

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 1 h

Score:

ca. 4

Max. score:

4

Reversibility:

not reversible

Remarks:

in 1-h exposure group

Irritation parameter:

erythema score

Basis:

mean

Time point:

24 h

Score:

ca. 4

Max. score:

4

Reversibility:

not reversible

Remarks:

in 1-h exposure group

Irritation parameter:

erythema score

Basis:

mean

Time point:

48 h

Score:

ca. 4

Max. score:

4

Reversibility:

not reversible

Remarks:

in 1-h exposure group

Irritation parameter:

erythema score

Basis:

mean

Time point:

72 h

Score:

ca. 4

Max. score:

4

Reversibility:

not reversible

Remarks:

in 1-h exposure group

Irritation parameter:

erythema score

Basis:

mean

Time point:

7 d

Score:

ca. 4

Max. score:

4

Reversibility:

not reversible

Remarks:

in 1-h exposure group

Irritation parameter:

erythema score

Basis:

mean

Time point:

14 d

Score:

ca. 4

Max. score:

4

Reversibility:

not reversible

Remarks:

in 1-h exposure group

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 1 h

Score:

ca. 4

Max. score:

4

Reversibility:

fully reversible within: 14 days in 1-h exposure group

Irritation parameter:

edema score

Basis:

mean

Time point:

24 h

Score:

ca. 4

Max. score:

4

Reversibility:

fully reversible within: 14 days in 1-h exposure group

Irritation parameter:

edema score

Basis:

mean

Time point:

48 h

Score:

ca. 3.66

Max. score:

4

Reversibility:

fully reversible within: 14 days in 1-h exposure group

Irritation parameter:

edema score

Basis:

mean

Time point:

72 h

Score:

ca. 3

Max. score:

4

Reversibility:

fully reversible within: 14 days in 1-h exposure group

Irritation parameter:

edema score

Basis:

mean

Time point:

7 d

Score:

ca. 1.66

Max. score:

4

Reversibility:

fully reversible within: 14 days in 1-h exposure group

Irritation parameter:

edema score

Basis:

mean

Time point:

14 d

Score:

ca. 0

Max. score:

4

Reversibility:

fully reversible within: 14 days in 1-h exposure group

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 1 h

Score:

ca. 0

Max. score:

4

Reversibility:

fully reversible

Remarks:

in 3-min exposure group

Irritation parameter:

erythema score

Basis:

mean

Time point:

24 h

Score:

ca. 1

Max. score:

4

Reversibility:

fully reversible

Remarks:

in 3-min exposure group

Irritation parameter:

erythema score

Basis:

mean

Time point:

48 h

Score:

ca. 1.33

Max. score:

4

Reversibility:

fully reversible

Remarks:

in 3-min exposure group

Irritation parameter:

erythema score

Basis:

mean

Time point:

72 h

Score:

ca. 1.66

Max. score:

4

Reversibility:

fully reversible

Remarks:

in 3-min exposure group

Irritation parameter:

erythema score

Basis:

mean

Time point:

7 d

Score:

ca. 0

Max. score:

4

Reversibility:

fully reversible

Remarks:

in 3-min exposure group

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 1 h

Score:

ca. 0

Max. score:

4

Reversibility:

fully reversible within: 7days in 3-min exposure group

Irritation parameter:

edema score

Basis:

mean

Time point:

24 h

Score:

ca. 0.33

Max. score:

4

Reversibility:

fully reversible within: 7days in 3-min exposure group

Irritation parameter:

edema score

Basis:

mean

Time point:

7 d

Score:

ca. 0

Max. score:

4

Reversibility:

fully reversible within: 7days in 3-min exposure group

Irritant / corrosive response data:

After three minutes exposure:
No adverse skin reaction were noted at any treated skin site one hour after the removal of the patches. Very slight or well-defined erythema had developed at two treated skin sites at the 24-hour observation and continued to be noted at all the treated sites at the 48 and 72-hour observations. Very slight edema was noted at one treated site at the 24 ad 48-hour observations and at two treated sites at the 72-hour 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 one hour 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-hour observation and continued to be noted at the 48, 72-hour and day seven 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 seven. On day fourteen sunken eschar was noted at all the treated skin sites. Severe edema was noted at all the treated sites one hour after the removal of the patches. The edema gradually decreased and appeared as very slight to slight on day seven. The oedema extended approximately 2 to 3 cm beyond all treated ski sites during this period. No edema was noted on day fourteen.

Primary dermal irritatin indices were not evaluated in this study, only individual animal qualitative scores were presented per time point.

Conclusions:

Based on the study results, the test substance was found to be corrosive to skin.

Executive summary:

A study was conducted to determine the skin irritation potential of the test substance in rabbits according to OECD guideline 404. 0.5 mL of test substance was applied under occlusive patches on the clipped dorsal area of a total of six New Zealand White rabbits per group. The animals were left for an exposure period of 3 min for three animals and 1 h for the other three animals. The residual test material was removed by gentle swabbing with cotton wool soaked in 3% (v/v) aqueous acetic acid followed by cotton wool soaked in distilled water. Approximately one h following removal of the patches, and 24, 48, 72 h and 7 and 14 days later, the test sites were examined for evidence of primary irritation and scored according to Draize (1959). In this study, no adverse skin reaction were noted at any treated skin site in the 3-min exposure group except slight erythema and edema at the treated sites up to the 72 h observation period. However, 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 one h after the removal of the patches. Eschar had developed at all treated skin sites at the 24-h observation period and continued to be present at the 48 and 72 h and day seven observation. Blanching and moderate erythema were also noted at all the treated skin sites during this period. On day 14, sunken eschar was noted at all the treated skin sites. Based on the study results, the test substance is considered to be corrosive to skin.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

disregarded due to major methodological deficiencies

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

significant methodological deficiencies

Remarks:

From a peer reviewed publication.

Principles of method if other than guideline:

Method: other: Draize test for TIC determination

GLP compliance:

no

Species:

rabbit

Amount / concentration applied:

Concentration: 0.1 % active substance
Amount applied: 0.1 ml

Number of animals or in vitro replicates:

5

Threshold Irritant Concentration (TIC) for dialkyldimethylammonium chloride (C8-C18) and
Didecyldimethylammonium chloride has been established. The concept of the threshold is introduced to indicate minimum
percentage concentration at which only mild irritation occurs as defined by the Draize scoring method. Thus, by
using a series of graded concentrations of each compound a measurement of this threshold is obtained:

Threshold Irritant Concentration (TIC) determined in the eyeof the rabbit.

Dialkyldimethylammonium chloride (C8-C18):
Conc.  No. of  Max. ave.   Adjective 
(%)     eyes     score     rating
____________________________________
0.063    5       4.4       Mild
0.125    5       7.2       Moderate
0.25     5       22.4      Severe
TIC = 0.063 

Didecyldimethylammonium chloride:
Conc.  No. of  Max. ave.   Adjective 
(%)     eyes     score     rating
_____________________________________
0.063    5       4.4       Mild
0.125    5      10.8       Moderate
0.25     5      20.8       Severe
0.5      5      33.6       Severe
TIC = 0.063

Reference: 
Duprey LP, Hoppe JO, report on Toxicity and Irritatiion Studies on Quaternary Ammonium Compounds, files of Sterling
-Winthrop Research Institute, unpublished, 1967.

Conclusions:

DDAC is expected to be severely damaging to eyes based on its corrosive nature. Concentrations as low as 0.1 to 0.5% are often irritating to conjunctivae and mucous membranes..

Executive summary:

DDAC is expected to be severely damaging to eyes based on its corrosive nature. Concentrations as low as 0.1 to 0.5% are often irritating to conjunctivae and mucous membranes..

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance is classified as skin corrosion, leading to classification as serious eye damage (Category 1)

Reason / purpose for cross-reference:

data waiving: supporting information

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation/corrosion

In an OECD Guideline 404 compliant study, 0.5 mL of test substance was applied under occlusive patches on the clipped dorsal area of a total of six New Zealand White rabbits per group. The animals were left for an exposure period of 3 min for three animals and 1 h for the other three animals. The residual test material was removed by gentle swabbing with cotton wool soaked in 3% (v/v) aqueous acetic acid followed by cotton wool soaked in distilled water. Approximately one h following removal of the patches, and 24, 48, 72 h and 7 and 14 days later, the test sites were examined for evidence of primary irritation and scored according to Draize (1959). In this study, no adverse skin reactions were noted at any treated skin site in the 3 min exposure group except slight erythema and oedema at the treated sites up to the 72 h observation period. However, after 1 h exposure, a light brown discoloration of the epidermis and slight haemorrhage of the dermal capillaries were noted at all treated skin sites one h after the removal of the patches. Eschar had developed at all treated skin sites at the 24 h observation period and continued to be present at the 48 and 72 h and day seven observation. Blanching and moderate erythema were also noted at all the treated skin sites during this period. On Day 14, sunken eschar was noted at all the treated skin sites. Based on the study results, the test substance is considered to be corrosive to skin (Safepharm, 1987).  

In a further OECD Guideline and EU Method compliant study, under GLP conditions, dorsal hair was removed by clipping in 6 animals and the neat test substance was applied to the skin under a semi-occlusive bandage. The animals were divided into two groups according to the exposure period: 3 min and 4 h. After removal of the patches, the skin is observed for signs of irritation. In this study, the 4 h exposure produced severe erythema and severe edema up to the 72 h observation period and the skin appeared rough, dry, scabbed with discoloration. The 3 min exposure produced slight erythema, slight to severe oedema up to 7 days and at end of 14 day observation period, the skin appeared dry, rough and leather-like. The mean score for oedema and erythema was 4 up to the observation period of 72 h. Based on the study results, the test substance was found to be corrosive (Hoechst, 1991).  

Further, DDAC is anticipated to be severely damaging to human skin based on its corrosive nature. The maximum concentration that is likely not produce irritating effect on intact skin is 0.1%. Irritation becomes manifest at concentrations of 1% and higher (Cutler and Drobeck, 1970).    

 

Eye irritation

The test substance is classified as corrosive to skin. Hence, for animal welfare reasons, testing for eye irritation has not been conducted and DDAC is considered to cause severe eye damage.  

Further, the substance is expected to be severely damaging to eyes based on its corrosive nature. Concentrations as low as 0.1 to 0.5% are often irritating to conjunctivae and mucous membranes (Cutler and Drobeck, 1970).  

Justification for classification or non-classification

Studies conducted in rabbit demonstrate that the test substance is corrosive to skin and warrants classification as Skin Corr. 1B - H314 (Causes severe skin burns and eye damage) according to EU CLP (Regulation EC/1272/2008) criteria. Testing for eye irritation was not conducted since the substance is proposed for classification as corrosive; severe eye irritation responses along with irreversible eye damage are expected.