Cyclohexyldimethylamine

Endpoint summary

Description of key information

Acute oral, inhalation and dermal studies are available.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Provides basic data; some details missing including dose levels.

Qualifier:

no guideline followed

Principles of method if other than guideline:

The test substance was administered to groups of male and female Sprague Dawley rats by oral gavage and observed for a period of 14 days.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Age: no data
- Weight at study initiation: 110 g
- Housing: During the observation period the rats were housed in stainless steel hanging cages with up to two rats of the same sex and dosage group per cage.

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 0.63ml/kg.

Doses:

Dosages ranged from 0.25 to 0.63ml/kg.

No. of animals per sex per dose:

10/sex/dose

Control animals:

no

Details on study design:

ADMINISTRATION: 
- Doses: 0.25-0.63 ml/kg
- Doses per time period: single 
- Post dose observation period: 14-days

EXAMINATIONS:
mortality/clinical signs
limited necropsy on all animals that died and on up to 3/sex/treatment of the survivors

Statistics:

No information provided

Preliminary study:

Not relevant

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 272 - < 289 mg/kg bw

Remarks on result:

other: Originally reported in ml/kg; mg/kg bw  determined using a density of 0.849 g/cm3.

Sex:

male

Dose descriptor:

LD50

Effect level:

289 mg/kg bw

95% CL:

> 221 - < 340

Remarks on result:

other: originally reported as 0.34 ml/kg bw, 95% confidence interval 0.26-0.40

Sex:

female

Dose descriptor:

LD50

Effect level:

272 mg/kg bw

95% CL:

> 238 - < 306

Remarks on result:

other: Originally reported as 0.32 ml/kg, 95% confidence interval 0.28-0.36

Mortality:

- Number of deaths at each dose: not specified
- Time of death: within 24 hours, and a few delayed deaths

Clinical signs:

other: decreased activity, ataxia, jerks, tremors, dyspnea, clonic convulsions, salivation and squinting. These signs usually lasted less than 24 hours.

Gross pathology:

(a) in the majority of animals that died: gastric lesions, suggestive of irritation, were observed, including red linear mucosal streaks or red discoloration of mucosa. An occasional erosion and one example of mucosal oedema was also observed.
(b) in some animals that survived: thin connective tissue adhesions in stomach serosa and varios adnexal structures were found in some animals. Mucosal keratinization of stomach was found in one animal.

Other findings:

No additional information provided

Gross examination of animals dying acutely or survivors at the end of the 14 day observation period, suggested that Polycat 8 was irritating to the stomach under the conditions of this study.

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Under the conditions of this study, the LD50 of the test substance was found to be between 272 and 289mg/kg bw. Based on this result, the test substance was considered to be a Category 3 toxicant and should have the signal word Danger and the hazard statement, H301: Toxic if swallowed associated with it. According to Directive 67/548/EEC, the test substance should be classified as Harmful and have the risk phrase R22: Harmful if swallowed associated with it.

Executive summary:

In a study conducted in 1979, the test substance, cyclohexyldimethylamine (DMCHA) was evaluated for its ability to induce toxicity when administered to male and female Sprague Dawley rats via oral gavage. The concentration administered ranged from 0.25 to 0.63 ml/kg. Following a single administration, the animals were observed for a 14 day post-exposure period.

Rats treated with DMCHA exhibited decreased activity, ataxia, jerks, tremors, dyspnea, clonic convulsions, salivation and squinting. These signs usually lasted less than 24 hours. Most deaths occurred within 24 hours after treatment although a few delayed deaths also occurred.

Gross examination of animals dying acutely and survivors at the end of the 14-day recovery period suggested that DMCHA, administered under the conditions of this study, was irritating to the stomach.

Under the conditions of this study, the LD₅₀ of the test substance was found to be between 272 and 289mg/kg bw. Based on this result, the test substance was considered to be a Category 3 toxicant and should have the signal word Danger and the hazard statement, H301: Toxic if swallowed associated with it. According to Directive 67/548/EEC, the test substance should be classified as Harmful and have the risk phrase R22: Harmful if swallowed associated with it.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

272 mg/kg bw

Quality of whole database:

Older proprietary study, considered sufficient for classification and hazard identification

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

11 to 30 November 1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Similar to guideline study; GLP. Six hour exposure rather than 4 hour.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

Exposed for 6 hours instead of 4 hours.

Principles of method if other than guideline:

not relevant

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Age: 8 weeks
- Weight at study initiation: 168.4-239.8 g (males), 120.9-143.0 g (females)
- Source: Charles River Breeding Laboratories, Inc., Kingston, NY.
- Housing: Rats were group housed prior to exposure and singly housed during the 2 week post-exposure period.
- Diet: Purina Certified Rodent Chow #5002 ad libitum, except during exposure.
- Water: available ad libitum.

IN-LIFE DATES: From: 11 November 1987 To: 30 November 1987

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Vehicle:

not specified

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Exposure chamber
- Exposure chamber volume: 157L
- Method of holding animals in test chamber: No data
- Source and rate of air: Vapors of DMCHA were generated using the glass J-tube method. Liquid test material was metered into the J-tube. The rate of air flow was approximately 30L per minute
- Method of conditioning air: Compressed air heated with a flameless heat torch to the minimum extent necessary passed through the J-tube to volatilize the test material.
- System of generating particulates/aerosols: No data
- Method of particle size determination: No data
- Treatment of exhaust air: No data
- Temperature, humidity, pressure in air chamber: Temperature: 24 ± 1°C, Humidity: 40 - 49%

TEST ATMOSPHERE
- Brief description of analytical method used: Airflow through each chamber was determined with a manometer, which was calibrated with a DTM-115 gas meter. The analytical concentration of DMCHA in the chamber was determined at least 3 times/exposure period by gas chromatography using a flame ionization detector. A 6 ft nickel column packed with 10% OV-11 on 100/120 Supelcoport was used. The gas chromatograph was calibrated with air standards of DMCHA. Air standards of known concentrations of the test substance were prepared by injecting measured volumes into bags containing measured volumes of dry, compressed air. The analytical system was checked prior to each exposure with at least one standard of known concentration.
- Samples taken from breathing zone: No data

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: No data
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): No data

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: No data

Analytical verification of test atmosphere concentrations:

yes

Remarks:

3 times/exposure period by gas chromatography with FID

Duration of exposure:

6 h

Remarks on duration:

Exposure period at the highest concentration was restricted to 150 minutes due to mortality

Concentrations:

actual: 88, 320, 1120 ppm; nominal: 106, 303, 1018 ppm

No. of animals per sex per dose:

5/sex/dose

Control animals:

no

Details on study design:

- airflow: ~ 12 air changes/hour
- Particle size: not applicable, vapour exposure
- Type or preparation of particles: vapour was generated using the glass J-tube method

EXAMINATIONS: 
-2 week post-exposure observation period mortality/clinical signs daily body weight prior to exposure and on day 2, 4, 8, 12 and 14/15
-ophthalmologic examination prior to exposure
-macroscopy on all animals 
-histopathology: in situ examination of the eyes at 320 ppm

Statistics:

no data

Preliminary study:

Not relevant

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 1 700 - < 5 800 mg/m³ air

Exp. duration:

6 h

Remarks on result:

other: LC50 = 1.7-5.8 mg/L

Mortality:

- Time of death: within 150 min at 1120 ppm, shortly after end of exposure at 320 ppm
- Number of deaths at each dose: 
dose   males   females
88       0/5      0/5
320      1/5      2/5
1120    5/5      5/5

Clinical signs:

other: 1120 ppm: labored respiration and body tremors during exposure in the visible animals 320 ppm:  (a) during exposure in the visible animals laboured respiration, soiling of the nose and mouth, rough hair coat and body tremors (b) post-exposure bilateral 

Body weight:

decreased 6-9% at 320 ppm, but recovery appparent within a week of treatment. Bodyweights unaffected at 88 ppm.

Gross pathology:

1120 ppm: generalized visceral congestion, soiling of the external nares by clear fluid, urine soiling of the perineum in half of the animals

320 ppm: (a) in animals that died, multiple dark foci in lungs, congestion of the liver, erosions and/or ulcers in the glandular portion of the stomach, hemolyzed blood in the digestive tract and facial and perineal soiling (b) survivors' eye lesions varying from slight haziness of the cornea to dense pale opacification of the cornea. Mineralisation of the corneal basement was noted in the eyes of rats having slight haziness of the corneas, the least severe lesion. This mineralization was present as a thin plaque involvoing large areas of the basement membrane. Rats having more severe involvement had much thicker mineralized plaques involving the corneal basement membrane accompanied by inflammation and neovascularization of hte cornea.
88 ppm:  no treatment-related effects

Other findings:

HISTOPATHOLOGY: mineralization of the corneal basement membrane of the eyes, inflammation (5/7) and neovascularization of the cornea (5/7), corneal ulcer (1/7) in the test group administered 320ppm test substance.

Due to the lethal effect of the test substasnce at the highest dose level, the test was terminated after 150 minutes of exposure.

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Under the conditions of this study, the LC50 was determined to be greater than 320ppm (equivalent to 1.7 mg/L) in both sexes. Based on these results, the test substance should be considered to be an Acute Toxicity Category 3 (Inhalation vapours) toxicant and have the hazard statement H331: Toxic if inhaled and the signal word, Danger. According to Directive 67/548/EEC, the test substance should be classified as toxic (T) and have the risk phrase, R23 Toxic by inhalation associated with it.

Executive summary:

In a study conducted by Nitschke et al, (1988) the test substance cyclohexyldimethylamine (DMCHA) was investigated for its ability to cause toxicity when administered to male and female Fischer 344 rats via the inhalation route. The animals were exposed via whole body exposure in exposure chambers at 3 concentrations, specifically, 88, 320 and 1120 ppm. In the top dose group, the exposure period was terminated at 150 minutes while in the two lower concentration groups, the animals were exposed for 6 hours, with a post-exposure observation period of two weeks.

At the highest concentration, 1120 ppm, all animals died within 150 minutes. Body tremors and labored respiration were observed prior to death. At 320 ppm, 1 male and 2 females died shortly after exposure. Tremors, laboured respiration and soiling of the nose and mouth were observed during exposure. Body weight decreased 6 to 9% immediately after exposure but recovered quickly. In animals sacrificed on test day 14, exposure-related lesions were observed in the eye only. Microscopically, slight to severe corneal opacities along with inflammation and neovascularization of the cornea were observed in these animals. These corneal opacities were judged likely to be irreversible although the lens and retina were unaffected. There were no real effects observed following exposure at 88ppm.

Under the conditions of this study, the LC₅₀ was determined to be 320 to 1120ppm (equivalent to 1.7 - 5.8 mg/L).

Based on these results, the test substance should be considered to be an Acute Toxicity Category 3 (Inhalation vapours) toxicant and have the hazard statement H331: Toxic if inhaled and the signal word, Danger. According to Directive 67/548/EEC, the test substance should be classified as toxic (T) and have the risk phrase, R23 Toxic by inhalation associated with it.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

1 700 mg/m³ air

Quality of whole database:

GLP study comparable to guideline

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

8th January 1986 to 30th January 1986.

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study, not GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Principles of method if other than guideline:

Not relevant

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Interfauna U.K. Limited, Wyton, Huntingdon.
- Age at study initiation: ten to fourteen weeks old.
- Weight at study initiation: Males: 200 - 254g
Females: 200 - 245g
- Fasting period before study: Not documented
- Housing: Housed in polypropylene cages with sawdust bedding.
- Diet (e.g. ad libitum): Rat and Mouse Expanded Diet No. 1 ad libitum
- Water (e.g. ad libitum): Mains drinking water ad libitum
- Acclimation period: Not documented

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 22°C
- Humidity (%): 45 - 60%
- Air changes (per hr): Approximately 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark

IN-LIFE DATES: From: 8 January 1986 To: 30 January 1986

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Back and flanks of each animal, approximately 6 x 12 cm.
- % coverage: Approximately 10%
- Type of wrap if used: A sheet of aluminium foil (7 x 4cm) was placed over the treatment area and occluded with a double layer of adhesive strapping (SLEEK) wrapped around the trunk of the rat.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes - the test area and surrounding hair were wiped with moist absorbant paper to remove any residual test sample.
- Time after start of exposure: After the 24 hour contact period

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.36, 0.43, 0.50 and 0.59 ml/kg.

Duration of exposure:

24 hours

Doses:

300, 360, 420, 500 mg/kg bw

No. of animals per sex per dose:

5/sex/dose

Control animals:

no

Details on study design:

EXAMINATIONS: 
14 days observation period mortality/clinical signs 1 and 4 hours after dosing and once daily thereafter body weights prior to dosing and on day 7 and 14 macroscopy on all animals.

Statistics:

Weil C.S. (1952), Biometrics 8, 249

Preliminary study:

Not relevant

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

380 mg/kg bw

Based on:

not specified

95% CL:

330 - 440

Remarks on result:

other: Three animals (1 male and 2 females) were found dead at the 4 hour observation and one male and female were found dead on day 1.

Mortality:

- Time of death: all within 1 day post-dose  
dose male  female  all
300   2/5    0/5   2/10
360   2/5    3/5   5/10
420   2/5    4/5   6/10
500   3/5    5/5   8/10

Clinical signs:

other: (a) during exposure: in majority hunched posture, pilo-erection, lethargy, ataxia, decreased respiratory rate or gasping respiration, ptosis, tail arching, (occasional) body tremors. In minority red/brown staining around the eyes and/or nose, tail lashing

Gross pathology:

(a)in animals that died: congested lungs at 360 and 420 mg/kg. Haemorrhage of the subcutis, dark staining or reddening of the treatment site at all doses in all animals dying during the study. In some of these animals the upper layer of skin was peeling away from the underneath skin.
(b) in survivors: eschar on the application site with dark areas below eschar formation

Other findings:

No additional results

In the preliminary range finding study, the mortalities recorded indicated a dermal LD50 in the range of 500 - 1000 mg/kg. However, mortalities were apparent soon after dosing the initially selected low dose group (500 mg/kg) and the selected dose levels were revised, making the 500 mg/kg the high dose group.

No additional findings were noted in the main test group.

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Under the conditions of the study, the dermal LD50 of DMCHA was determined to be 380 mg/kg (330 - 440 mg/kg 95% confidence limits). Based on these results, the test substance should be classified as a Category 3 acute dermal toxicant according to Regulation EC No. 1272/2008 and should have the signal word Danger and the hazard statement H301: Toxic if swallowed associated with it. In accordance with Directive 67/548/EEC, the test substance should be classified as Toxic (T) and have the risk phrase R24 Toxic in contact with skin associated with it.

Executive summary:

In a study conducted by Jones and Collier (1986), the test substance, cyclohexyldimethylamine (DMCHA), was examined for its ability to cause acute dermal toxicity when applied to the backs and flanks of male and female Sprague-Dawley rats. A preliminary study was performed to determine the appropriate dose level to use, with 300, 360, 420 and 500 mg/kg being selected as the dose concentrations to use in the main study. The test substance was applied under an occlusive dressing and left in place for 24 hours. Following the 24 hour contact period, the dressing was removed and the test site and surrounding hair was washed with moist absorbent paper to remove any remaining test substance. Deaths were dose related with 2 deaths at 300 mg/kg, 5 deaths at 360 mg/kg, 6 deaths at 420 mg/kg and 8 deaths at 500 mg/kg. All deaths occurred within the first 24 hours and survivors all appeared normal after 3 days, with the exception of skin damage at the treatment site. Signs of toxicity included ataxia, tremors, tail arching and convulsions. At necropsy after 14 days, survivors showed no abnormalities of internal organs but all showed extensive skin damage. Under the conditions of the study, the dermal LD₅₀ of DMCHA was determined to be 380 mg/kg (330 - 440 mg/kg 95% confidence limits). Based on these results, the test substance should be classified as a Category 3 acute dermal toxicant according to Regulation EC No. 1272/2008 and should have the signal word Danger and the hazard statement H311: Toxic in contact with skin

associated with it. In accordance with Directive 67/548/EEC, the test substance should be classified as Toxic (T) and have the risk phrase R24 Toxic in contact with skin associated with it.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

380 mg/kg bw

Quality of whole database:

GLP and guideline compliant study

Additional information

Acute Oral Toxicity:

In a study conducted in 1979, the test substance, cyclohexyldimethylamine (DMCHA) was evaluated for its ability to induce toxicity when administered to male and female Sprague Dawley rats via oral gavage. The dose administered ranged from 0.25 to 0.63 ml/kg. Following a single administration, the animals were observed for a 14 day post-exposure period.

Rats treated with DMCHA

exhibited decreased activity, ataxia, jerks, tremors, dyspnoea, clonic convulsions, salivation and squinting. These signs usually lasted less than 24 hours. Most deaths occurred within 24 hours after treatment although a few delayed deaths also occurred.

Gross examination of animals dying acutely and survivors at the end of the 14-day recovery period suggested that DMCHA, administered under the conditions of this study, was irritating to the stomach.

Under the conditions of this study, the LD₅₀ for the test substance was found to be between 272 and 289 mg/kg bw. Based on this result, the test substance was considered to be a Category 3 toxicant and should have the signal word Danger and the hazard statement, H301: Toxic if swallowed associated with it. According to Directive 67/548/EEC, the test substance should be classified as Harmful and have the risk phrase R22: Harmful if swallowed associated with it.

Acute Inhalation Toxicity:

In a study conducted by Nitschke et al, (1988) the test substance cyclohexyldimethylamine (DMCHA) was investigated for its ability to cause toxicity when administered to male and female Fischer 344 rats via the inhalation route. The animals were exposed via whole body exposure in exposure chambers at 3 concentrations, specifically, 88, 320 and 1120 ppm. In the top dose group, the exposure period was terminated at 150 minutes while in the two lower concentration groups, the animals were exposed for 6 hours, with a post-exposure observation period of two weeks.

At the highest concentration, 1120 ppm, all animals died within 150 minutes. Body tremors and labored respiration were observed prior to death. At 320 ppm, 1 male and 2 females died shortly after exposure. Tremors, laboured respiration and soiling of the nose and mouth were observed during exposure. Body weight decreased 6 to 9% immediately after exposure but recovered quickly. In animals sacrificed on test day 14, exposure-related lesions were observed in the eye only. Microscopically, slight to severe corneal opacities along with inflammation and neovascularization of the cornea were observed in these animals. These corneal opacities were judged likely to be irreversible although the lens and retina were unaffected. There were no real effects observed following exposure at 88ppm.

Under the conditions of this study, the LC₅₀ was determined to be 320 to 1120ppm (equivalent to 1.7 - 5.8 mg/L). Based on these results, the test substance should be considered to be an Acute Toxicity Category 3 (Inhalation vapours) toxicant and have the hazard statement H331: Toxic if inhaled and the signal word, Danger. According to Directive 67/548/EEC, the test substance should be classified as toxic (T) and have the risk phrase, R23 Toxic by inhalation associated with it

Acute Dermal Toxicity:

In a study conducted by Jones and Collier (1986), the test substance, cyclohexyldimethylamine (DMCHA), was examined for its ability to cause acute dermal toxicity when applied to the backs and flanks of male and female Sprague-Dawley rats. A preliminary study was performed to determine the appropriate dose level to use, with 300, 360, 420 and 500mg/kg being selected as the dose concentrations to use in the main study. The test substance was applied under an occlusive dressing and left in place for 24 hours. Following the 24 hour contact period, the dressing was removed and the test site and surrounding hair was washed with moist absorbent paper to remove any remaining test substance. Deaths were dose related with 2 deaths at 300 mg/kg, 5 deaths at 360 mg/kg, 6 deaths at 420 mg/kg and 8 deaths at 500 mg/kg. All deaths occurred within the first 24 hours and survivors all appeared normal after 3 days, with the exception of skin damage at the treatment site. Signs of toxicity included ataxia, tremors, tail arching and convulsions. At necropsy after 14 days, survivors showed no abnormalities of internal organs but all showed extensive skin damage. Under the conditions of the study, the dermal LD₅₀ of DMCHA was determined to be 380 mg/kg (330 - 440 mg/kg 95% confidence limits). Based on these results, the test substance should be classified as a Category 3 acute dermal toxicant according to Regulation EC No. 1272/2008 and should have the signal word Danger and the hazard statement H311: Toxic in contact with skin associated with it. In accordance with Directive 67/548/EEC, the test substance should be classified as Toxic (T) and have the risk phrase R24 Toxic in contact with skin associated with it.

Justification for classification or non-classification

Acute Oral Toxicity:

Based on the results of the key study, the substance, cyclohexyldimethylamine (DMCHA0 should be classified as a Category 3 toxicant and should have the signal word Danger and the hazard statement, H301: Toxic if swallowed associated with it. According to Directive 67/548/EEC, the test substance should be classified as Harmful and have the risk phrase R22: Harmful if swallowed associated with it.

Acute Inhalation Toxicity:

Based on the results of the key study, the substance, cyclohexyldimethylamine (DMCHA) should be considered to be an Acute Toxicity Category 3 (Inhalation vapours) toxicant and have the hazard statement H331: Toxic if inhaled and the signal word, Danger. According to Directive 67/548/EEC, the test substance should be classified as toxic (T) and have the risk phrase, R23 Toxic by inhalation associated with it

Acute Dermal Toxicity:

Based on the results of the key study, the substance should be classified as an Acute Toxicity Category 3, with the hazard statement H311: Toxic in contact with skin and the Signal word Danger associated with it, in accordance with Regulation EC No. 1272/2008. According to Directive 67/548/EEC, the test substance should be classified as Toxic (T) and have the risk phrase R24 Toxic in contact with skin associated with it.