Cetrimonium chloride

Endpoint summary

Description of key information

Based on the results from the 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

Reference

Reference 1

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.

Reason / purpose for cross-reference:

read-across source

Qualifier:

equivalent or similar to guideline

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.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

From 16 April, 1990 to 19 April, 1990

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Remarks:

purity not specified

Principles of method if other than guideline:

Six healthy New Zealand albino rabbits (2 males and 4 females) were clipped free of hair over approximately 10% of their body surface. 0.5 mL of test substance was placed on the site of approximately 25x25 mm and occluded for 24 h. The occluded coverings were then removed and the test site was wiped to prevent further exposure. The test sites were evaluated 24 and 72 h after initial exposure and scored according to the method of 16 CFR 1500.41.

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Davidson's Mill Farm, S. Brunswick, NJ
- Housing: Individually in suspended stainless steel caging with mesh floors
- Diet: Pelleted Purina rabbit chow ad libitum
- Water: Tap water supplied by automatic water system
- Acclimation period: 15, 16 or 48 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23

Type of coverage:

occlusive

Preparation of test site:

other: skin was clipped

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

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

Duration of treatment / exposure:

24 hours

Observation period:

72 hours

Number of animals:

Six (2 males and 4 females)

Details on study design:

TEST SITE
- Area of exposure: 25x25 mm in a 25 mm Hilltop chamber
- % coverage: 10% of the total body area
- Type of wrap if used: Durapore tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Test sites were gently wiped clean (not rinsed) of any residual test substance
- Time after start of exposure: 24 h

SCORING SYSTEM: According to FHSA primary skin irritation scoring system, 16 CFR 1500.41

Irritation parameter:

erythema score

Basis:

mean

Time point:

24 h

Score:

ca. 2.5

Max. score:

4

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

24 h

Score:

ca. 2.33

Max. score:

4

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Basis:

mean

Time point:

72 h

Score:

ca. 2.83

Max. score:

4

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

72 h

Score:

ca. 2.67

Max. score:

4

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Basis:

mean

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

edema score

Basis:

mean

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24/72 h

Score:

ca. 5.42

Max. score:

8

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

For erythema-eschar formation and edema formation: See table for “Table for Irritation score”

Table for Irritation score

Rabbit no.	24 hours (Intact)	72 hours (Intact)
6373	2^a,b/3	3^a/3
6374	2^a,c/2	3^c,b/3
6375	3^a,c/2	3/3
6376	3^c/2	3^c/3
6377	3^a,c/2	3^c/2
6378	2^a,c/3	2^c/2
Total:	15/14	17/16
Mean:	2.5/2.33	2.83/2.67

^aThickening of skin; ^bBlack staining; ^cBrown discolouration

PDI = 5.42 (Mean erythema scores + mean edema scores for 24 and 72 h divided by 2)

Interpretation of results:

study cannot be used for classification

Remarks:

Study conducted with a very low dilution/concentration

Conclusions:

Under the study conditions, the test substance was found to be irritating to skin.

Executive summary:

A study was conducted to assess the skin irritation potential of undiluted test substance, C16 TMAC (5% active in water) on rabbit skin. Rabbits were prepared by clipping the skin free of hair. Four test application sites, approximately 25 x 25 mm, were delineated on the upper left, lower left, upper right and lower right flanks of the animal. 0.5 mL undiluted test substance was deposited into a 25 mm Hilltop Chamber and placed on each site. The entire area was then wrapped with tape. Patches were removed after 24 h of exposure. Skin sites were evaluated at 24 and 72 h after initial exposure and scored according to the method of 16 CFR 1500.41. The test substance was considered to be an irritant with a high erythema and oedema scores along with thickening of skin, black staining and brown discoloration observed after 72 h and a mean primary dermal irritation index (PDII) of 5.42. Under the study conditions, the test substance was found to be irritating to skin (Shapiro, 1990).

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 (corrosive)

Eye irritation

Link to relevant study records

Reference

Reference 1

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

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

From February, 1986 to June, 1986

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Certificate of analysis of test substance not included in report.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

other: Kleinrusse Chbb: HM/Fa. Thomae

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2197 - 2317 g

Vehicle:

water

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1 mL
- Concentration (if solution): 2%

Duration of treatment / exposure:

Solution was applied at test start and no rinsing was conducted.

Observation period (in vivo):

14 days

Number of animals or in vitro replicates:

4 males

Details on study design:

SCORING SYSTEM: According to Draize JH, Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. Ass. of Food and Drug Officials of the US, pp 49-52 (1959) at 1, 6, 24, 48, 72 and 96 h, as well 8, 11 and 14 days post-application.

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

4 animals

Time point:

24/48/72 h

Score:

ca. 0.33

Max. score:

4

Reversibility:

fully reversible within: 14 d

Remarks on result:

positive indication of irritation

Irritation parameter:

iris score

Basis:

mean

Remarks:

4 animals

Time point:

24/48/72 h

Score:

ca. 0.67

Max. score:

4

Reversibility:

fully reversible within: 14 d

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Remarks:

4 animals

Time point:

24/48/72 h

Score:

ca. 2.67

Max. score:

4

Reversibility:

fully reversible within: 11 d

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

4 animals

Time point:

24/48/72 h

Score:

ca. 1.08

Max. score:

4

Reversibility:

fully reversible within: 11 d

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

(exudation)

Basis:

mean

Remarks:

4 animals

Time point:

24/48/72 h

Score:

ca. 2.75

Max. score:

4

Reversibility:

fully reversible within: 11 d

Remarks on result:

positive indication of irritation

Irritation parameter:

overall irritation score

Remarks on result:

not measured/tested

Irritation parameter:

maximum mean total score (MMTS)

Remarks on result:

not measured/tested

The effects noted in the study are summarised in the following table:

Endpoint	1hour	6 hours	24 hours	48 hours	72 hours	96 hours	8 d	11 d	14 d
Opacity grade	0	0.5	0.5	0.25	0.25	0.25	0.25	0.25	0
Opacity surface	0	0.5	0.5	1.0	0.5	0.5	0.25	0.25	0
Redness	1.5	2.0	2.25	3.0	2.75	1.75	0.25	0	-
Chemosis	1.75	2.0	1.5	1.0	0.75	0.25	0	0	-
Exsudation	2.75	3.0	3.0	2.75	2.50	1.50	0	0	-

Interpretation of results:

other: Category 2 (irritant)

Remarks:

based on CLP criteria

Conclusions:

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

Executive summary:

A study was performed to assess the eye irritation potential of test substance, C16 TMAC (2% active in water) in rabbits, according to OECD Guideline 405, in compliance with GLP. 0.1 mL of the test substance (diluted at 2%) was placed in the conjunctival sac of the right eye of four rabbits. The other eye of each rabbit remained untreated and served as a control. Ocular lesions were evaluated at 1, 6, 24, 48, 72 and 96 h as well 8, 11 and 14 days post-application according to the Draize (1959) method. In two rabbits, a slight corneal reaction was observed 2 days after the start of the study but there were no effects on the iris in any of the animals. Moderate to severe effects were however noted on the conjunctiva of the rabbits, with full recovery at 11 days. Under the study conditions, the test substance was considered to be highly irritating to the eyes (Kastner, 1986).

Reference 3

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

From 11 June, 1990 to 14 June, 1990

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

according to the Federal guideline: 16 CFR 1500.42.

Qualifier:

according to guideline

Guideline:

other: Federal guidelines: 16 CFR 1500.42

Deviations:

no

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Davidson's Mill Farm, S. Brunswick, NJ
- Housing: individually in suspended stainless steel caging with mesh floors
- Diet: Pelleted Purina rabbit chow ad libitum
- Water (e.g. ad libitum): Tap water supplied by automatic water system
- Acclimation period: 8 or 45 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-26

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1 mL
- Concentration (if solution): 5%

Duration of treatment / exposure:

24 h

Observation period (in vivo):

72 h

Number of animals or in vitro replicates:

6 (3 males and 3 females)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No
- Time after start of exposure: 24, 48 and 72 h

SCORING SYSTEM: Draize score; The eye scores were further classified by the modified system of Kay and Calandra.

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Time point:

24 h

Score:

ca. 53

Max. score:

110

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Time point:

48 h

Score:

ca. 59.7

Max. score:

110

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Time point:

72 h

Score:

ca. 58.3

Max. score:

110

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

6 animals

Time point:

24/48/72 h

Score:

ca. 1.83

Max. score:

4

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritation parameter:

other: corneal area

Basis:

mean

Remarks:

6 animals

Time point:

24/48/72 h

Score:

ca. 3.5

Max. score:

4

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritation parameter:

iris score

Basis:

mean

Remarks:

6 animals

Time point:

24/48/72 h

Score:

ca. 1

Max. score:

2

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Remarks:

6 animals

Time point:

24/48/72 h

Score:

ca. 2.83

Max. score:

3

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

6 animals

Time point:

24/48/72 h

Score:

ca. 3.22

Max. score:

4

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

(discharge)

Basis:

mean

Remarks:

6 animals

Time point:

24/48/72 h

Score:

ca. 3

Max. score:

3

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

All treated eyes had corneal opacity, iritis and conjunctival irritation during the 24 to 72 h test period.

Other effects:

Apart from the eye irritation effects, there were no signs of gross toxicity, adverse pharmacological effects or abnormal behaviour.

See the attached background material:

Table-1: Score for ocular lesions

Table-2: Scale for scoring ocular lesions

Table-3: Classification of eye score

Interpretation of results:

other: Serious eye damage (Category 1)

Remarks:

based on the CLP criteria

Conclusions:

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

Executive summary:

A study was performed to assess the potential of test substance, C16 TMAC (5% active in water) to cause eye irritation in rabbit eyes, according to the Federal guideline: 16 CFR 1500.42.. 0.1 mL of undiluted test substance was placed in the conjunctival sac of the right or left eye of six rabbits. The other eye of each rabbit remained untreated and served as a control. After instillation of the test substance, ocular lesions were evaluated at 24, 48 and 72 h according to the Draize method. The eye irritation scores were further classified by the modified method of Kay and Calandra.All treated eyes had corneal opacity, iritis and conjunctival irritation during the 24-72 h test period.Apart from the eye irritation response, there were no signs of gross toxicity, adverse pharmacologic effects or abnormal behavior. The 24 h maximum mean total score (MMTS) was 53. Under the study conditions, the test substance was considered to be extremely irritating to the eyes (Shapiro, 1990).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin

Study 1: A study was conducted to determine dermal irritation potential of the read across substance, C16-18 and C18-unsatd. TMAC (50% active in aqueous/isopropanol solution), in rabbits, according to a method similar to OECD Guideline 404. In the study, six rabbits (both sexes) were treated with 0.5 mL of undiluted read across substance 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 d 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 with an average irritation score was 5.4/8. After 10 d, 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 d. Under the test conditions, the undiluted read across substance was concluded to be non-corrosive after 1 h of occlusive exposure, but corrosive after 4 h of occlusive exposure (van Beek, 1982). Based on the results of the read across study, similar corrosion potential can be expected for the test substance.

Study 2:

A study was conducted to assess the skin irritation potential of undiluted C16 TMAC (purity not specified) on rabbit skin. Rabbits were prepared by clipping the skin free of hair. Four test application sites, approximately 25 x 25 mm, were delineated on the upper left, lower left, upper right and lower right flanks of the animal. 0.5 mL undiluted test substance was deposited into a 25 mm Hilltop Chamber and placed on each site. The entire area was then wrapped with tape. Patches were removed after 24 h of exposure. Skin sites were evaluated at 24 and 72 h after initial exposure and scored according to the method of 16 CFR 1500.41. The test substance was considered to be an irritant with a high erythema and oedema scores along with thickening of skin, black staining and brown discoloration observed after 72 h and a mean primary dermal irritation index (PDII) of 5.42 (Shapiro, 1990).

Eyes

Study 1:

A study was performed to assess the potential of C16 TMAC (5% active in water) to cause eye irritation in rabbit eyes, according to the Federal guideline: 16 CFR 1500.42.. 0.1 mL of undiluted test substance was placed in the conjunctival sac of the right or left eye of six rabbits. The other eye of each rabbit remained untreated and served as a control. After instillation of the test substance, ocular lesions were evaluated at 24, 48 and 72 h according to the Draize method. The eye irritation scores were further classified by the modified method of Kay and Calandra.All treated eyes had corneal opacity, iritis and conjunctival irritation during the 24-72 h test period.Apart from the eye irritation response, there were no signs of gross toxicity, adverse pharmacologic effects or abnormal behavior. The 24 h maximum mean total score (MMTS) was 53. Based on the scoring system used, the test substance was considered to be extremely irritating (Shapiro, 1990).

Study 2:

A study was performed to assess the eye irritation potential of C16 TMAC (2% active in water) in rabbits, according to OECD Guideline 405, in compliance with GLP. 0.1 mL of the test substance (diluted at 2%) was placed in the conjunctival sac of the right eye of four rabbits. The other eye of each rabbit remained untreated and served as a control. Ocular lesions were evaluated at 1, 6, 24, 48, 72 and 96 h as well 8, 11 and 14 days post-application according to the Draize (1959) method. In two rabbits, a slight corneal reaction was observed 2 days after the start of the study but there were no effects on the iris in any of the animals. Moderate to severe effects were however noted on the conjunctiva of the rabbits, with full recovery at 11 days. Under the study conditions and based on the scoring system used, the test substance (2% dilution) was considered to be highly irritating to the eyes.

In the above two studies, eye irritation responses at concentrations up to 5% a.i. were moderate, and at 2% a.i., were reversible (Kästner, 1986). Data available on other TMAC substances tested at higher concentrations of active ingredient were found to have corrosive effects, suggesting that solutions containing a higher concentration of C16 TMAC may also be corrosive. This is consistent with the observed corrosive effects on the skin.

Justification for classification or non-classification

Based on the results of the in vivo skin and eye irritation studies, the test substance warrants a a '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.

With regard to respiratory tract irritation, although C16 TMAC is a very corrosive substance, its low vapour pressure prohibits the occurrence of respiratory irritation by vapour. Further, the classification of corrosive is already considered to implicitly cover the potential of RTI and therefore an additional Cat.3 is considered to be superfluous (Guidance CLP Ch. 3.8.2.5).