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Endpoint summary

Description of key information

Based on the available information, C12-14 TMAC is considered to be corrosive to skin and causes serious damage to the 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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Study not GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

no

Specific details on test material used for the study:

- Präpagen 2916 (Hoe S 2916)
- Composition: ca. 40% C12-14 alkylmethylammonium chloride, ca. 1% amine/aminehydrochloride with mentioned C chain, ca. 1% salt, ca. 60% water
- Form: Clear liquid
- Storage: in the dark at 2°C

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hoechst AG, conventional breeding
- Weight at study initiation: 2.0 - 2.3 kg
- Housing: individual cages in climatised room
- Diet (e.g. ad libitum): ERKA Z 6000 (Robert Koch oHG, Germany)
- Water (e.g. ad libitum): deinosed chlorinated water

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24°C
- Humidity (%): 30-70%

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

Undiluted

Duration of treatment / exposure:

4 h

Observation period:

14 d

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: 20 cm2
- Type of wrap if used: Hansamed bandage and semi-occlusive wrap

REMOVAL OF TEST SUBSTANCE
- Washing (if done): careful removal of remaining test substance after exposure period
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
(indicate if minutes, hours or days): 0.5-1, 24, 48 and 72 h then 7 and 14 d after patch removal

SCORING SYSTEM:
- Method of calculation: as per OECD guideline

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 2.53

Max. score:

4

Reversibility:

not fully reversible within: 14 d

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 1.67

Max. score:

4

Reversibility:

fully reversible within: 14 d

Remarks on result:

probability of mild irritation

Irritant / corrosive response data:

After the 4 h exposure period, moderate to severe erythema gradually developped, leading in part to the appearance of scabs after 48 h. There was pronounced edema in all animals. Seven days after application, the treated skin was hardened. Large and small detachments were seen. In 4 out of 6 animals, scars remained on the skin.

Individual results are presented in the attachment entitled 'Präpagen skin irritation results'.

Interpretation of results:

other: Category 1C (corrosive) based on CLP criteria

Conclusions:

Under the study conditions, the test substance was considered to be irritating to skin. Considering the results obtained with the test substance containing 40% of the a.i. along with the evidence from a study with read across substance, Coco TMAC, it is proposed that 100% C12-14 TMAC can be considered to be corrosive to rabbit skin.

Executive summary:

A study was conducted to determine the skin irritation potential of the test substance, C12-14 TMAC (active ingredient 40%), in rabbit, according to OECD 404 Guideline. Six New Zealand White rabbits were exposed to undiluted substance (i.e., 40% test substance) on their shaved flank. The exposure period was 4 h, using a Hansplast patch and semi-occlusive bandaging. After 4 h, remaining test substance was carefully removed. The treated skin area was observed after 0.5-1, 24, 48 and 72 h then 7 and 14 d. After the 4 h exposure period, moderate to severe erythema gradually developped, leading in part to the appearance of scabs after 48 h. There was pronounced edema in all animals. Seven days after application, the treated skin was hardened. Large and small detachments were seen. In 4 out of 6 animals, scars remained on the skin. Based on the strong effects observed (scarring), the test substance was considered to be irritating to skin (Jung and Weigand, 1982). Considering the results obtained with the test substance containing 40% of the a.i. along with the evidence from a study with read across substance, Coco TMAC, it is proposed that 100% C12-14 TMAC can be considered to be corrosive to rabbit skin.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

From 23 February, 1988 to 8 March, 1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

KL2 due to RA

Justification for type of information:

Refer to the Quaternary ammonium salts (QAS) category or section 13 of IUCLID for details on the category justification. The study with the read across substance is considered sufficient to fulfil the information requirements as further explained in the provided endpoint summary.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute 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: Mohican Valley Rabbitry; Loudonville, Ohio
- Age at study initiation: Young adult
- Weight at study initiation: 2,736 to 3,450 g at study initiation
- Housing: Individual suspended wire-mesh cages. The animals were maintained in accordance with the recommendations contained in the "guide for care and use of laboratory animals" NIH publication, No. 85023.
- Diet: Purina Certified Rabbit Chow #5322
- Water: Tap water
- Acclimation period: 7 d

ENVIRONMENTAL CONDITIONS
- Temperature : 71-74 °F
- Humidity (%): 50-74%
- Photoperiod (hrs dark / hrs light): 12 h light/12 h dark

IN-LIFE DATES: From: 23 February, 1988 to 8 March, 1988

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.5 mL/site

Duration of treatment / exposure:

4 h

Observation period:

14 d

Number of animals:

3 males and 3 females

Details on study design:

TEST SITE
0.5 mL dose was applied under secured 1 x 1 inch2 guaze patches that were overwrapped with a gauze binder secured with dermiform tape. Plastic restraint collars were applied and remained on the animals for the duration of the exposure period.

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: At the end of 4 h, the collars and bandages were removed and the sites wiped with wet disposable paper towels.

SCORING SYSTEM: Draize

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24 and 72 hours

Score:

5.6

Max. score:

8

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: severly irritating (due to not completely reversible reactions (moderate irritation was still present in one rabbit); in addition desquamation was noted on all sites late in the study period and fissuring was present on two sites

Irritation parameter:

erythema score

Basis:

mean

Time point:

72 h

Score:

ca. 2.8

Reversibility:

fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

mean

Time point:

72 h

Score:

ca. 2.2

Reversibility:

fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 3

Max. score:

4

Reversibility:

not fully reversible within: 14 d

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

ca. 3

Max. score:

4

Reversibility:

fully reversible within: 14 d

Remarks on result:

probability of moderate irritation

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

ca. 2.6

Max. score:

4

Reversibility:

fully reversible within: 14 d

Remarks on result:

probability of moderate irritation

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

ca. 3

Max. score:

4

Reversibility:

fully reversible within: 14 d

Remarks on result:

probability of moderate irritation

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

ca. 3

Max. score:

4

Reversibility:

fully reversible within: 14 d

Remarks on result:

probability of moderate irritation

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

ca. 3

Max. score:

4

Reversibility:

fully reversible within: 14 d

Remarks on result:

probability of moderate irritation

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 3.6

Max. score:

4

Reversibility:

not fully reversible within: 14 d

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

ca. 1.6

Max. score:

4

Reversibility:

fully reversible within: 14 d

Remarks on result:

probability of mild irritation

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

ca. 2

Max. score:

4

Reversibility:

fully reversible within: 14 d

Remarks on result:

probability of moderate irritation

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

ca. 3

Max. score:

4

Reversibility:

fully reversible within: 14 d

Remarks on result:

probability of moderate irritation

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

ca. 3.6

Max. score:

4

Reversibility:

fully reversible within: 14 d

Remarks on result:

probability of moderate irritation

Irritation parameter:

edema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

ca. 2.3

Max. score:

4

Reversibility:

fully reversible within: 14 d

Remarks on result:

probability of moderate irritation

Irritant / corrosive response data:

Average erythema score for all animals at 24h: 3; 48h: 3; 72h: 2.8
Average edema score for all animals at 24h: 3.2; 48h: 2.8; 72h: 2.2
Reversibility: Yes, the highest levels of irritation occurred two to three days after dosing and irritation subsequently decreased although moderate reactions still persisted in one animal after study Day 12.
The test substance induced moderate erythema and moderate to severe oedema on all sites. Irritation decreased as the study progressed, however, moderate irritation was present in one rabbit (score: erythema:2; edema:1) through study Day 11.

Other effects:

Desquamation was noted on all sites late in the study period and fissuring was present on two sites.

Mortality: One rabbit was sacrificed in extremis on Day 3 due to broken back.

Body weight: No remarkable changes occurred.

Interpretation of results:

other: Category 1C (corrosive) based on CLP criteria

Conclusions:

Under the study conditions, the test substance (containing 33% a.i.) was found to be severly irritating to rabbit skin; therefore, 100% Coco TMAC can be considered to be corrosive. Based on the read across approach, a similar corrosive behaviour can be expected for C12-14 TMAC.

Executive summary:

A study was conducted to determine the skin irritation potential of the read across substance, Coco TMAC (active ingredient 33%), in New Zealand White rabbits according to OECD 404 Guideline, in compliance with GLP. Six animals were treated with 0.5 mL undiluted test substance (33%) in a semi-occlusive patch (1” X 1” gauze) that was overwrapped with a gauze binder and secured with dermiform tape. Plastic restraint collars were applied and remained on the animals for the duration of the 4 h exposure period, after which the tape and test substance were removed. The Draize classification scoring criteria was used to evaluate the irritation potential. Application sites were observed for erythema and oedema at 4, 24, 48 and 72 h after exposure and then daily up to 14 d. The test substance induced moderate erythema and moderate to severe edema on all sites. Remission of irritation signs occurred as the study progressed, however, moderate irritation was still present in one rabbit after study Day 12 (erythema: 2 ‘slight’; edema:1 ‘barely perceptible’). In addition, desquamation was noted on all sites late in the study period and fissuring was present on two sites. The Primary Irritation Index was calculated to be 5.6 (indicative of moderate irritation). Under the study conditions, due to persistence of irritation reactions in one animal as well as desquamation on all sites and fissuring on 2 sites, the test substance is considered to be severely irritating. Considering the results obtained with the test substance containing 33% of the a.i., it is proposed that 100% Coco TMAC can be considered to be corrosive to rabbit skin (Naas, 1988). Based on the read across approach, a similar corrosive behaviour can be expected for C12-14 TMAC.

Reference 3

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 for cross-reference:

data waiving: supporting information

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Study not GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

no

Specific details on test material used for the study:

- Präpagen 2916 (Hoe S 2916)
- Composition: ca. 40% C12-14 alkylmethylammonium chloride, ca. 1% amine/aminehydrochloride with mentioned C chain, ca. 1% salt, ca. 60% water
- Form: Clear liquid
- Storage: in the dark at 2°C

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Hoechst AG, conventional breeding
- Weight at study initiation: 2.2 - 2.5 kg
- Housing: individual cages in climatised room
- Diet (e.g. ad libitum): ERKA Z 6000 (Robert Koch oHG, Germany)
- Water (e.g. ad libitum): deinosed chlorinated water
Lighting: 12 h daily

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24°C
- Humidity (%): 30-70%

Controls:

other: Untreated eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):0.1 ml
- Concentration (if solution): undiluted

Duration of treatment / exposure:

24 h

Observation period (in vivo):

7 d

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with physiological saline at 37°C
- Time after start of exposure: 24 h

SCORING SYSTEM: as per OECD guideline

TOOL USED TO ASSESS SCORE: biomicroscope

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 2.1

Max. score:

4

Reversibility:

not fully reversible within: 7 d

Remarks on result:

positive indication of irritation

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 1.3

Max. score:

4

Reversibility:

not fully reversible within: 7 d

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 2.1

Max. score:

4

Reversibility:

not fully reversible within: 7 d

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

(swelling)

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 3.2

Max. score:

4

Reversibility:

not fully reversible within: 7 d

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Irritant / corrosive response data:

Corneal opacity was observed in all animals at the 1 h time point and was still present after 7 d when vascularisation of the cornea was also seen in 2/3 rabbits. Effects on the iris appeared after 1 h and increased in intensity until the 7 d timepoint when they were still scored at 2 in all rabbits. Conjunctival redness and swelling was also present from 1 h to the end of the study, with no reversibility of the symptoms. After 7 d, the nictating membrane was milky in all treated eyes. There was also bleeding of the conjunctiva and hair loss in a large area around the eyes.

Individual results are presented in the attachment entitled 'Präpagen eye irritation'.

Interpretation of results:

other: Category 1 (irreversible effects on the eye) based on CLP criteria

Conclusions:

Under the study conditions, the test substance was considered to be severely irritating to eyes.

Executive summary:

A study was conducted to determine the eye irritation potential of the test substance, C12-14 TMAC (active ingredient 40%) in rabbit, according to OECD 405 Guideline. Three New Zealand White rabbits were exposed to undiluted substance (i.e., 40% test substance) applied as a 0.1 mL drop in the left conjunctival sack. The right eye was untreated and served as control. After 24 h of exposure, the eyes were gently washed with physiological saline solution at 37°C. Observations for corneal opacity, effects on the iris and conjunctival reddening/swelling were made 1, 4, 24, 48 and 72 h after eye washing, then after 7 d. Corneal opacity was observed in all animals at the 1 h time point and was still present after 7 d when vascularisation of the cornea was also seen in 2/3 rabbits. Effects on the iris appeared after 1 h and increased in intensity until the 7 d timepoint when they were still scored at 2 in all rabbits. Conjunctival redness and swelling was also present from 1 h to the end of the study, with no reversibility of the symptoms. After 7 d, the nictating membrane was milky in all treated eyes. There was also bleeding of the conjunctiva and hair loss in a large area around the eyes. Under the study conditions, the test substance was considered to be severely irritating to eyes (Jung and Weigand, 1982).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

Study 1: A study was conducted to determine the skin irritation potential of the test substance, C12-14 TMAC (active ingredient 40%), in rabbit, according to OECD 404 Guideline. Six New Zealand White rabbits were exposed to undiluted substance (i.e., 40% test substance) on their shaved flank. The exposure period was 4 h, using a Hansplast patch and semi-occlusive bandaging. After 4 h, remaining test substance was carefully removed. The treated skin area was observed after 0.5-1, 24, 48 and 72 h then 7 and 14 d. After the 4 h exposure period, moderate to severe erythema gradually developped, leading in part to the appearance of scabs after 48 h. There was pronounced edema in all animals. Seven days after application, the treated skin was hardened. Large and small detachments were seen. In 4 out of 6 animals, scars remained on the skin. Based on the strong effects observed (scarring), the test substance was considered to be irritating to skin (Jung and Weigand, 1982).

Study 2: A study was conducted to determine the skin irritation potential of the read across substance, Coco TMAC (active ingredient 33%), in New Zealand White rabbits according to OECD 404 Guideline, in compliance with GLP. Six animals were treated with 0.5 mL undiluted test substance (33%) in a semi-occlusive patch (1” X 1” gauze) that was overwrapped with a gauze binder and secured with dermiform tape. Plastic restraint collars were applied and remained on the animals for the duration of the 4 h exposure period, after which the tape and test substance were removed. The Draize classification scoring criteria was used to evaluate the irritation potential. Application sites were observed for erythema and oedema at 4, 24, 48 and 72 h after exposure and then daily up to 14 d. The test substance induced moderate erythema and moderate to severe edema on all sites. Remission of irritation signs occurred as the study progressed, however, moderate irritation was still present in one rabbit after study Day 12 (erythema: 2 ‘slight’; edema:1 ‘barely perceptible’). In addition, desquamation was noted on all sites late in the study period and fissuring was present on two sites. The Primary Irritation Index was calculated to be 5.6 (indicative of moderate irritation). Under the study conditions, due to persistence of irritation reactions in one animal as well as desquamation on all sites and fissuring on 2 sites, the test substance is considered to be severely irritating. Considering the results obtained with the test substance containing 33% of the a.i., it is proposed that 100% Coco TMAC can be considered to be corrosive to rabbit skin (Naas, 1988).

Overall, considering the results obtained with the test substance containing 40% of the a.i. along with the evidence from a study with read across substance, it is proposed that 100% C12-14 TMAC can be considered to be corrosive to rabbit skin.

Eye irritation

A study was conducted to determine the eye irritation potential of the test substance, C12-14 TMAC (active ingredient 40%) in rabbit, according to OECD 405 Guideline. Three New Zealand White rabbits were exposed to undiluted substance (i.e., 40% test substance) applied as a 0.1 mL drop in the left conjunctival sack. The right eye was untreated and served as control. After 24 h of exposure, the eyes were gently washed with physiological saline solution at 37°C. Observations for corneal opacity, effects on the iris and conjunctival reddening/swelling were made 1, 4, 24, 48 and 72 h after eye washing, then after 7 d. Corneal opacity was observed in all animals at the 1 h time point and was still present after 7 d when vascularisation of the cornea was also seen in 2/3 rabbits. Effects on the iris appeared after 1 h and increased in intensity until the 7 d timepoint when they were still scored at 2 in all rabbits. Conjunctival redness and swelling was also present from 1 h to the end of the study, with no reversibility of the symptoms. After 7 d, the nictating membrane was milky in all treated eyes. There was also bleeding of the conjunctiva and hair loss in a large area around the eyes. Under the study conditions, the test substance was considered to be severely irritating to eyes (Jung and Weigand, 1982).

Justification for classification or non-classification

Skin

Based on the effects observed in in vivo skin irritation studies conducted with the test substance as well as read across substance, 100% concentrations of C12 -14 TMAC can be considered to be classified as 'skin corrosive category 1C; H314 - causes severe skin burns and eye damage' according to EU CLP criteria (Regulation EC 1272/2008).

Eye

Based on the effects observed in a study with test substance containing 40% active ingredient, 100% concentrations of C12-14 TMAC can be considered to be classified as 'Eye damage 1; H318- causes serious eye damage' according to EU CLP criteria (Regulation EC 1272/2008). Labelling for this endpoint is covered by the above classifications for skin effects.