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Administrative data

Description of key information

Based on the results from the in vitro and read across in vivo irritation studies, the test substance  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

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Justification for type of information:
Refer to the Quaternary ammonium salts (QAS) category or section 13 of IUCLID for details on the category justification.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Type of coverage:
occlusive
Preparation of test site:
other: intact and abraded
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.5 mL of undiluted test substance (50% pure)
Duration of treatment / exposure:
4 or 1 h
Observation period:
4 or 1 hour, 48 h and 10 days
Number of animals:
Six males and females
Details on study design:
Six healthy adult New Zealand White albino rabbits (M/F) were used for the test. 24 hours prior to applying the test substance, the hair was removed from the back of the animals with electric clippers in such a way as to avoid abrasions.

An amount of 0.5 mL of the undiluted test substance was brought on the intact skin under a surgical patch measuring 1 x 1 inch. The patches were fixed to the application site by means of adhesive tape and the entire trunk of the rabbits was wrapped with an impervious material to maintain the test patches in position and to retard evaporation of volatile substances.

Each rabbit was treated on the intact skin. The abrasions were minor incisions through the stratum corneum, but not sufficiently deep to disturb the derma or to produce bleeding.

After an exposure period of 4 or 1 hour the patches and the test substance applied were removed and the resulting skin reactions were evaluated by the method of Draize scoring. A second reading was made 48 hours later.
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 1 h
Score:
0.85
Max. score:
8
Reversibility:
fully reversible within: 10 days
Remarks on result:
other: Study II, following exposure period of 1 hour
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 4 h
Score:
4
Max. score:
8
Reversibility:
not reversible
Remarks:
within 10 days
Remarks on result:
other: Study I, following exposure period of 4 hours
Irritation parameter:
erythema score
Remarks:
4 h exposure
Basis:
mean
Time point:
48 h
Score:
3.84
Max. score:
4
Reversibility:
not fully reversible within: 10 days
Remarks on result:
other: well-defined to moderate erythema
Irritation parameter:
erythema score
Remarks:
1 h exposure
Basis:
mean
Time point:
48 h
Score:
1.08
Max. score:
4
Reversibility:
fully reversible within: 10 days
Remarks on result:
other: very slight to moderate erythema
Irritation parameter:
edema score
Remarks:
1 h exposure
Basis:
mean
Time point:
48 h
Score:
ca. 0.33
Max. score:
4
Reversibility:
fully reversible within: 10 dys
Remarks on result:
other: very slight to slight edema
Irritation parameter:
edema score
Remarks:
4 h exposure
Basis:
mean
Time point:
48 h
Score:
ca. 1.58
Max. score:
4
Reversibility:
not fully reversible within: 10 days
Remarks on result:
other: very slight or slight edema
Irritation parameter:
overall irritation score
Remarks:
4 h exposure
Basis:
mean
Time point:
48 h
Score:
ca. 5.4
Max. score:
8
Reversibility:
not reversible
Remarks:
within 10 days
Remarks on result:
other: Corrosive to skin
Irritation parameter:
overall irritation score
Remarks:
1 h exposure
Basis:
mean
Time point:
48 h
Score:
ca. 1.25
Max. score:
8
Reversibility:
fully reversible within: 10 days
Remarks on result:
other: corrosive to skin
Irritation parameter:
erythema score
Basis:
mean
Time point:
24 h
Remarks on result:
not measured/tested
Irritation parameter:
erythema score
Basis:
mean
Time point:
72 h
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Basis:
mean
Time point:
72 h
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Basis:
mean
Time point:
24 h
Remarks on result:
not measured/tested
Irritant / corrosive response data:
Observations in 4 hours test:
- After 4 hours: Very slight to well-defined erythema, very slight ischemia and very slight edema
- After 48 hours: Well-defined to moderate erythema, very slight to slight ischemia and very slight or slight edema
- After 10 days: Slight to distinct incrustation and decreased hair growth

Observations in 1 h test:
After 1 h: Very slight erythema
After 48 h: Very slight to moderate erythema and very slight or slight edema
After 10 d: No skin effects were observed

For result tables, kindly refer to the attached background material section of the IUCLID.

Interpretation of results:
other: Category 1C based on CLP criteria
Conclusions:
Based on the results of the read across study, the undiluted test substance is considered to be corrosive to skin.
Executive summary:

A study was conducted to determine the skin irritation potential of the read across substance, C16 -18 and C18 -unsatd. TMAC (50% active) in rabbits, according to a method similar to OECD Guideline 204. Six rabbits (both sexes) were treated with 0.5 mL of undiluted read across substance (50% active ingredient) in an occlusive patch fixed with adhesive tape and wrapped with an impervious material, for 4 h. Observations were made at 4 h, 48 h and 10 days post-exposure. If the read across substance appeared to be corrosive after 4 h, another study was conducted with a 1 h exposure period under similar test conditions. The Draize scoring criteria was used for evaluating the corrosion potential. At 4 h, very slight to well-defined erythema, very slight ischemia and very slight oedema were observed, with an average irritation score of 4/8. At 48 h, there was well-defined to moderate erythema, very slight to slight ischemia and very slight or slight oedema and the average irritation score was 5.4/8. After 10 days, slight to distinct incrustation and decreased hair growth was observed. After an exposure period of 1 h, very slight erythema was observed with an average irritation score of 0.85/8. After 48 h, there was very slight to moderate erythema and very slight or slight oedema and the average irritation score was 1.25/8. No skin effects were observed after 10 days. Under the study conditions, the undiluted read across substance (50% active ingredient) was corrosive after 4 h of occlusive exposure. Based on the results of the read across study, similar corrosive potential is expected for the test substance.

Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
From 24 August, 2001 to 01 September, 2001
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Study was conducted according to acceptable scientific principles; in compliance with GLP. However, because the test substance is a surfactant, a second step (dye binding) should have been performed.
Qualifier:
according to
Guideline:
other: Rat Skin Transcutaneous Electrical Resistance (TER) Test INVITTOX no. 115
Principles of method if other than guideline:
The skin corrosivity potential of the test substance was assessed using the Transcutaneous Electrical Resistance Assay (TER). This method is based on the fact that corrosive substances produce an irreversible loss of normal stratum comeum integrity and function, which can be measured as a reduction in the inherent transcutaneous electrical resistance (TER) below a corrosive threshold level (i.e., 5kΩ).
GLP compliance:
yes (incl. certificate)
Species:
rat
Strain:
Wistar
Details on test animals and environmental conditions:
Male Wistar rats (Crl: (WI) BR), obtained from Charles River (UK) Limited, Margate, Kent, were used for the in vitro TER assay.
Type of coverage:
open
Preparation of test site:
other: Skin discs, obtained from the pelts of humanely killed young Crl (WI) BR Wistar strain rats
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
A volume of 150 µL of the test substance was applied to the inner epidermal surface using an automatic pipettor
Duration of treatment / exposure:
1, 4 and 24 h
Observation period:
1, 4 and 24 h
Details on study design:
SKIN DISC PREPARATION:
The animals were humanely killed by inhalation of a rising concentration of CO2 followed by cervical dislocation. The animals were in the telogen phase of hair growth and little or no hair growth was visible. The quality of the stratum corneum was critical to the success of the assay and so the stage of hair growth was controlled by using animals of exactly the correct age. When the animals had been humanely killed the dorsal skin was removed from each rat as a single pelt. Care was taken during the procedure to avoid unnecessary damage to the pelt. Excess fat was removed and the pelt mounted, epidermal side uppermost, onto a polytetrafluoroethylene (PTFE) tube. The tissue was secured in place using a rubber "O" ring. Excess tissue was trimmed away and the "O" ring/PTFE interface sealed with soft paraffin wax. The tube was supported by a clamp inside a labelled 30 ml glass receptacle containing 10 mL electrolyte solution (1 54 mM MgSO4).
Each disc had to give a resistance value of between 10 kΩ and 25 kΩ in order for the remainder of the pelt to be used in the assay.


TEST SUBSTANCE APPLICATION:
The test substance was applied to the epidermal surface of three skin discs per time point. The test substance was applied for contact periods of 1 h, 4 h and 24 h. The test substane was used as supplied. A volume of 150 µL was applied to the inner epidermal surface using an automatic pipettor.
At the end of the exposure period, the test substance was removed by washing the skin disc with a jet of warm tap water for approximately 10 seconds until no further test substance could be removed.


CONTROLS:
As part of a quality control procedure, a positive and negative control disc were assayed. The positive control was hydrochloric acid (approximately 36%) and the negative control was sterile distilled water. The contact period for the positive and negative controls was 24 h.


DETERMINATION OF TRANSCUTANEOUS ELECTRICAL RESISTANCE (TER):
The TER was measured using a Wheatstone Bridge with a low voltage alternating current. Prior to measurement of the resistance, the surface tension of the skin disc was reduced by adding a sufficient volume of 70% ethanol to cover the epidermis. The ethanol was removed by inverting the tube after approximately 3 secs. The PTFE tube was then placed in the labelled receptor chamber and the tissue was hydrated by the addition of 3 mL MgSO4 solution (154 mM) to the inside of the PTFE tube. Any air bubbles present were dislodged by tapping the tube. The stainless steel electrodes of the databridge were placed on either side of the skin disc. The measurement was taken and a value in Ω/kΩ per skin disc was displayed on the databridge display. The mean TER for the skin discs was calculated for each time point.
Irritation / corrosion parameter:
transcutaneous electrical resistance (in kΩ)
Run / experiment:
Mean
Value:
7
Remarks on result:
other: Time point: 1 h. Standard deviation = 3.8
Irritation / corrosion parameter:
transcutaneous electrical resistance (in kΩ)
Run / experiment:
Mean
Value:
2.6
Remarks on result:
other: Time point: 4 h, Standard deviation = 2.2
Irritation / corrosion parameter:
transcutaneous electrical resistance (in kΩ)
Run / experiment:
Mean
Value:
2.2
Remarks on result:
other: Time point: 24 h. Standard deviation = 3.8

According to the guideline INVITTOX no. 115, in case TER values below 5 kilo-Ohm are found, and in case the test substance is a surfactant, then a dye binding study (Sulforrhodamine B) should have been performed to determine whether this would be a false positive result. This has not been done.

Interpretation of results:
other: Category1 (corrosive) based on CLP criteria
Conclusions:
Under the study conditions, the test substance was considered to have the potential to be corrosive to skin.
Executive summary:

An in vitro transcutaneous electrical resistance (TER) assay was conducted to assess the skin corrosivity potential of the test substance, C16-18 TMAC (50% active ingredient) using skin discs obtained from the pelts of humanely killed young Crl (WI) BR Wistar rats. The test substance was applied to the epidermal surface of three skin discs per contact period, 1, 4, and 24 hours. At the end of the contact period the test substance was removed using a jet of warm tap water. Corrosive substances are found to produce an irreversible loss of normal stratum corneum integrity and function, which can be measured as a reduction in the inherent TER. A threshold value of 5 kΩ has been established below which substances are considered likely to be corrosive in vivo. The mean electrical resistance measured using low voltage alternating current electronic databridge after 1, 4 and 24 hours was 7, 2.6 and 2.2 kΩ. Under the study conditions, the test substance was considered to have the potential to be corrosive to skin (Sanders, 2002).

Endpoint:
skin corrosion: 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
Reason / purpose:
data waiving: supporting information
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Referenceopen allclose all

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:
data waiving: supporting information
Endpoint:
eye irritation: in 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:
data waiving: supporting information
Endpoint conclusion
Endpoint conclusion:
no study available

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin

Study 1: Anin vitrotranscutaneous electrical resistance (TER) assay was conducted to assess the skin corrosivity potential of the test substance, C16-18 TMAC (50% active ingredient) using skin discs obtained from the pelts of humanely killed young Crl (WI) BR Wistar rats. The test substance was applied to the epidermal surface of three skin discs per contact period, 1, 4, and 24 hours. At the end of the contact period the test substance was removed using a jet of warm tap water. Corrosive substances are found to produce an irreversible loss of normal stratum corneum integrity and function, which can be measured as a reduction in the inherent TER. A threshold value of 5 kΩ has been established below which substances are considered likely to be corrosivein vivo. The mean electrical resistance measured using low voltage alternating current electronic databridge after 1, 4 and 24 hours was 7, 2.6 and 2.2 kΩ. Under the study conditions, the test substance was considered to have the potential to be corrosive to skin (Sanders, 2002).

Study 2: A study was conducted to determine the skin irritation potential of the test substance, C16 -18 and C18 -unsatd. TMAC (50% active) in rabbits, according to a method similar to OECD Guideline 204. Six rabbits (both sexes) were treated with 0.5 mL of undiluted test substance (50% active ingredient) in an occlusive patch fixed with adhesive tape and wrapped with an impervious material, for 4 h. Observations were made at 4 h, 48 h and 10 days post-exposure. If the test substance appeared to be corrosive after 4 h, another study was conducted with a 1 h exposure period under similar test conditions. The Draize scoring criteria was used for evaluating the corrosion potential. At 4 h, very slight to well-defined erythema, very slight ischemia and very slight oedema were observed, with an average irritation score of 4/8. At 48 h, there was well-defined to moderate erythema, very slight to slight ischemia and very slight or slight oedema and the average irritation score was 5.4/8. After 10 days, slight to distinct incrustation and decreased hair growth was observed. After an exposure period of 1 h, very slight erythema was observed with an average irritation score of 0.85/8. After 48 h, there was very slight to moderate erythema and very slight or slight oedema and the average irritation score was 1.25/8. No skin effects were observed after 10 days. Under the study conditions, the undiluted test substance (50% active ingredient) was corrosive after 4 h of occlusive exposure.

Eye

In accordance with Annex VII, Section 8.2, Column 2, eye irritation studydoes not need to be conducted because the substance is classified as corrosive to the skin (Category 1C).


Justification for classification or non-classification

Based on the available results from in vitro and in vivo read across studies, the test substance warrants a corrosive, 'Skin Corr. 1C; H314: Causes severe skin burns and eye damage' as well as serious eye damage, 'Eye dam. 1; H31: Causes serious eye damage' classification according to the EU CLP criteria (Regulation EC 1272/2008). Labelling for this endpoint is covered by the above classifications for skin effects.