Amines, N-C12-18-alkyltrimethylenedi-

Endpoint summary

Description of key information

Available studies result to GHS classification Category 3 for acute oral toxicity (LD50 between 50 and 300 mg/kg bw) with a LD50 cut-off of 300 mg/kg bw. Acute dermal toxicity LD50 is > 2000 mg/kgbw. There is no data available on acute toxicity via inhalation.

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:

2007-11-21 to 2008-01-22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Principles of method if other than guideline:

not applicable

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

other: HsdRccHan: WIST (Full-Barrier)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelmann GmbH, D-33178 Borchen
- Weight at study initiation:
Step 1: 168 g (1 animal)
Step 2: 170-186 g
Step 3: 141-177 g
Step 4: 135-158 g
Step 5: 128-131 g

- Fasting period before study: overnight and 3-4 hours after dosing
- Housing: macrolon cages on Altromin saw fibre bedding
- Diet: ad libitum (Altromin 1324 (TPF)
- Water: ad libitum (drinking water)
- Acclimation period: at least 5 days
- Other: marked individually by tail painting, SPF animals

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 55 +/- 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

cotton seed oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle:
Step 1: 1.0 g/ 5 mL
Step 2: 0.3 g/ 10 mL
Step 3: 0.3 g/ 10 mL
Step 4: 0.1 g/ 20 mL
Step 5: 0.1 g/ 20 mL
- Amount of vehicle: 10 mL/ kg body weight
- Justification for choice of vehicle: non-toxic and lipophil
- Lot/batch no. : Lot 067K0116, Sigma Chemicals

MAXIMUM DOSE VOLUME APPLIED: 1.86 mL

DOSAGE PREPARATION : freshly mixed prior to administration

CLASS METHOD
- Rationale for the selection of the starting dose:
preliminary test with one animal performed (2000 mg/kg), due to immeadiate preacute lethality
the starting dose was choosen to be 300 mg/kg bw

Doses:

Step 1: 2000 mg/kg bw
Step 2: 300 mg/kg bw
Step 3: 300 mg/kg bw
Step 4: 50 mg/kg bw
Step 5: 50 mg/kg bw

No. of animals per sex per dose:

Step 1 (2000 mg/kg bw): 1 female rat
Step 2 (300 mg/kg bw): 3 female rats
Step 3 (300 mg/kg bw): 3 female rats
Step 4 (50 mg/kg bw): 3 female rats
Step 5 (50 mg/kg bw): 3 female rats

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: A careful clinical examination was made several times on the day of dosing.
Parts of this were at least three observations within the first four hours post-dose.
Animals were observed once a day thereafter.
The animals were weighed prior to the administration and once a week thereafter.

- Necropsy of survivors performed: yes

- Other examinations performed: Cage side observations included changes in the skin and fur, eyes and mucous membranes.
Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity
and behaviour pattern were examined. Particular attention was directed to observations of tremor,
convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Statistics:

not applicable

Sex:

female

Dose descriptor:

approximate LD50

Effect level:

300 mg/kg bw

Remarks on result:

other: acute toxic class method; according to GHS (Globally Harmonized Classification System) the test item N-coco-1,3-diaminopropane was classified into Category 3

Mortality:

Step 1 (2000 mg/kg bw, 1 female rat): within 1 h 30 min post-dose the animal was found dead
Step 2 (300 mg/kg bw): no deaths observed within the observation period
Step 3 (300 mg/kg bw): Animal 2 was found dead five days and animal 3 three days post-dose
Step 4 and 5 ( 50 mg/kg bw): no deaths observed within the observation period

Clinical signs:

other: see remarks on results including tables and figures

Gross pathology:

Animal no. 1 of step 1 (2000 mg/ kg bw):
The stomach showed haemorrhage with a foamy content. The small intestine
also showed haemorrhage with a bloody content. The large intestine and appendix were bloody.
Animal no.2 of step 3 (300 mg/ kg bw):
The animal was found dead in a lateral position and exhibited piloerection.The anus was smeared with
faeces.
Animal no. 3 of step 3 (300 mg/ kg bw):
The stomach was bloody. The small intestine was slightly bloody.

Signs of toxicity related to dose level used, time of onset and duration:

Animal no. 1 of step 1 (2000 mg/kg bw): 30 min post-dose: moderately reduced spontaneous activity, salivation, face down position.1 h 30 min post-dose: this animal was found dead.

Animal no. 1 of step 2 (300 mg/kg bw): 25 min post-dose: slightly reduced spontaneous activity, apathy, piloerection.1 h 45 min post-dose: slightly reduced spontaneous activity, piloerection, half eyelid-closure. 5 h 45 min post-dose: slightly reduced spontaneous activity, piloerection, sunken flank. 22 h 45 min as well as 28 h 45 min post-dose: slightly reduced spontaneous activity, piloerection, sunken flank, diarrhoea. 46 h 45 min post-dose: slightly reduced spontaneous activity, piloerection, diarrhoea, bloody snout, bloody mouth. 50 h 45 min post-dose: slightly reduced spontaneous activity, piloerection, diarrhoea, weight loss. 78 h 15 min post-dose: piloerection, diarrhoea, weight loss. 98 h 10 min post-dose: slightly reduced spontaneous activity, piloerection, diarrhoea, heavy breathing (rattling). 119 h 45 min post-dose: slightly reduced spontaneous activity, piloerection, apathy, weight loss. 143 h 45 min post-dose: apathy, piloerection.166 h 45 min post-dose: weight gain.

Animal No. 2 and 3 of step 2 (300 mg/kg bw): 30 min post-dose: slightly reduced spontaneous activity, apathy, salivation. 2 h 15 min post-dose: slightly reduced spontaneous activity (animal no. 3), moderately reduced spontaneous activity (animal no. 2), piloerection, half eyelid-closure. 4 h 15 min post-dose: moderately reduced spontaneous activity, piloerection. 23 h 15 min post-dose: slightly reduced spontaneous activity, piloerection. 28 h 15 min post-dose: moderately reduced spontaneous activity, piloerection, half eyelid-closure. 2 days post-dose until the end of the observation period: no further symptoms were observed.

Animal no. 1 of step 3 (300 mg/kg bw): 15 min post-dose: slightly reduced spontaneous activity, apathy, piloerection. 2 h as well as 4 h 30 min, 22 h post-dose: moderately reduced spontaneous activity, apathy, piloerection, half eyelid-closure. 47 h post-dose: moderately reduced spontaneous activity, apathy, piloerection, half eyelid-closure, diarrhoea, bloody snout, anal discharge. 71 h post-dose: slightly reduced spontaneous activity, apathy, piloerection, diarrhoea, weight loss. 97 h post-dose: moderately reduced spontaneous activity, apathy, piloerection, diarrhoea, weight loss. 121 h post-dose: slightly reduced spontaneous activity, piloerection, diarrhoea. 144 h post-dose: slightly reduced spontaneous activity, piloerection. 7 days post-dose until the end of the observation period: no further symptoms were observed.

Animal no. 2 of step 3 (300 mg/kg bw): 15 min post-dose: slightly reduced spontaneous activity, apathy, piloerection. 2 h as well as 4 h, 22 h post-dose: moderately reduced spontaneous activity, apathy, piloerection, half eyelid-closure. 47 h post-dose: moderately reduced spontaneous activity, apathy, piloerection, half eyelid-closure, diarrhoea, anal discharge. 71 h post-dose: slightly reduced spontaneous activity, apathy, piloerection, diarrhoea, weight loss. 97 h post-dose: severely reduced spontaneous activity, piloerection, diarrhoea, weight loss. 5 days post-dose the animal was found dead.

Animal no.3 of step 3 (300 mg/kg bw): 15 min post-dose: slightly reduced spontaneous activity, apathy, piloerection. 2 h as well as 4 h, 22 h post-dose: moderately reduced spontaneous activity, apathy, piloerection, half eyelid-closure. 47 h post-dose: moderately reduced spontaneous activity, apathy, piloerection, half eyelid-closure, diarrhoea, anal discharge, bloody snout.3 days post-dose the animal was found dead.

Animal no. 1, 2 and 3 of step 4 and 5 (50 mg/kg bw): No compound related mortality was recorded for any animal.

Absolute body weights in g :

Animal No.	Sex	Day 0	Day 7	Day 14
Step 1 (2000 mg/kg bw)
1	female	168	This animal was found dead.
Step 2 (300 mg/kg bw)
1	female	170	150	190
2	female	180	189	205
3	female	186	196	213
Step 3 (300 mg/kg bw)
1	female	177	180	201
2	female	141	92-this animal was found dead
3	female	149	This animal was found dead.
Step 4 (50 mg/kg bw)
1	female	135	138	142
2	female	158	191	206
3	female	158	183	197
Step 5 (50 mg/kg bw)
1	female	128	162	177
2	female	131	161	176
3	female	130	163	174

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Considering the reported data of this toxicity test it can be stated that the test item N-Coco-1,3-diaminopropane showed acute oral toxic characteristics.
According to GHS (Globally Harmonized Classification System) the test item N-Coco-1,3-diaminopropane was classified into Category 3 (LD50 cutoff:300 mg/kg bw).

Executive summary:

The acute toxic class method for oral toxicity was performed on nulliparous female HsdRccHan:WIST rats, who received a single exposure of N-Coco-1,3-diaminopropane via oral gavage.

A careful clinical examination was made several times on the day of dosing. Parts of this were at least three observations within the first four hours post-dose. Animals were observed once a day thereafter for 14 days. Cage side observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Particular attention was directed to observations of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma. At the end of the observation period the animals were sacrificed by an overdosage of pentobarbital. All animals were subjected to gross necropsy. All gross pathological changes were recorded.

In step 1 single female rat was dosed by oral gavage with 2000 mg N-coco-1,3-diaminopropane/ kg body weight in cotton seed oil. Severe, immediate toxicity indicated by salivation, face down position and moderately reduced spontaneous activity was observed in this animal, followed by death at 1 h and 30 min post-dose. In step 2 three female rats were dosed with 300 mg N-coco-1,3-diaminopropane/ kg body weight. Animal 1 showed severe signs of toxicity indicated by immediate piloerection followed by half eyelid closure, sunken flank, diarrhoea, bloody snout and mouth, weight loss and heavy breathing . 7 days post-dosing the animal gained weight again and recovered. Animal 2 and 3 showed reduction in spontaneous activity, apathy, salvation, piloerection and half eyelid-closure shortly after dosing. 2 days post-dose until the end of the observation period no further symptoms were evident. In step 3 three female rats were dosed with 300 mg N-coco-1,3 -diaminopropane/ kg body weight. Observed signs of toxicity of animal 1 were reduced spontaneous activity, piloerection, apathy, half eyelid-closure, diarrhoea, bloody snout, anal discharge and weight loss until 7 days post-dose. The animal showed no symptoms thereafter. Animal 2 of step 3 displayed increasing signs of toxicity indicated by reduced spontaneous activity, piloerection, apathy, half eyelid-closure, diarrhoea, anal discharge as well as weight loss and was found dead on day 5 post-dose. Animal 3 of step 3 displayed increasing signs of toxicity indicated by reduced spontaneous activity, piloerection, apathy, half eyelid-closure, diarrhoea, bloody snout, anal discharge and weight loss and was found dead on day 3 post-dose. Animal no. 1, 2 and 3 of step 4 and 5 received 50 mg N-coco-1,3-diaminopropane/ kg body weight by oral gavage. No compound related mortality was recorded for any of the animals.

According to the toxic class regime no further testing was required.

Following pathological changes were observed in the step 1 animal (2000 mg/kg bw): The stomach showed haemorrhage with a foamy content. The small intestine also showed haemorrhage with a bloody content. The large intestine and appendix were bloody. Animal 2 of step 3 (300 mg/kg bw) that was found dead after 5 days in a lateral position exhibited piloerection. Its anus was smeared with faeces. Animal no. 3 of step 3 (300 mg/ kg bw) had a bloody stomach. Its small intestine was slightly bloody.

Considering the reported data of this toxicity test it can be stated that the test item N-coco-1,3-diaminopropane showed acute oral toxic characteristics. On basis of the test results and in conformity with the criteria given in Annex VI of the Directive 2001/59/EC the substance should be classified as toxic. According to GHS (Globally Harmonized Classification System) the test item N-Coco-1,3-diaminopropane was classified into Category 3 (LD₅₀ cut-off: 300 mg/kg bw).

The acute oral toxicity test was conducted under GLP according to the guidelines for the acute toxic class method OECD 423, EU method B1.tris and OPPTS 870.110 without deviation.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

300 mg/kg bw

Quality of whole database:

The study is GLP compliant and has Klimisch score 1

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study was performed pre-GLP and not according to standard protocol but comparable with OECD402. The animals were exposed to the test substance was under occlusion and the area of expsoure was 30%. Necropsy is only performed on the that died during the observation period. The substance is corrosive to skin and eyes but in this part of the study nothing is mentioned about skin damage.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Principles of method if other than guideline:

The test aniamls were exposed under occlusion and the test ietm covered 30% of the body surface.

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: H . A . R . E . - Rabbits for Research, Hewitt, N.J., US (H.A.R.E. - Rabbits i s a USDA approved supplier. )
- Age at study initiation: no data
- Weight at study initiation: no data
- Fasting period before study: not applicable
- Housing: individually in wire mesh bottom cages.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum if 5 days

ENVIRONMENTAL CONDITIONS
no data

IN-LIFE DATES:
no data

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: back and flanks
- % coverage: 30
- Type of wrap if used: The occlusive binder consisted of a layer of plastic wrap, a protective cloth and stockinette binder, all securely held in place with masking tape. The occlusive binder is applied to maintain contact and minimize evaporation of the applied test article .

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The exposure sites were then gently wiped with clean gauze to remove as much nonabsorbed test article as possible.
- Time after start of exposure: After an exposure period of 24 hours.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2g/kg
- Concentration (if solution): -
- Constant volume or concentration used: yes

Duration of exposure:

24h

Doses:

2g/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Body weights were recorded on the initial day of testing and at study termination or day of death.
- Necropsy of survivors performed: no

Statistics:

E . L . Crow, Biometrika, 43, 423-435 (1956)

Preliminary study:

not peformed

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

One animal died during the 14 day observation period on day 13

Clinical signs:

other: not reported

Gross pathology:

not reported

Other findings:

not reported

Interpretation of results:

Category 5 based on GHS criteria

Remarks:

Migrated information

Conclusions:

One animal died on day 13. The LD50 for duomeen C is therefore > 2000 mg/kg bw

Executive summary:

The acute dermal toxicity Duomeen C was tested in New Zealand White Rabbits according to a study design similar to OECD 402. The back and flanks of 5 male and 5 female rabbits were clipped, constituting about 30% of the total body surface. Just prior of the application test substance, the skin surface was abraded in 3 of the males and 2 of the females. The animals received 2000 mg/kg undiluted test material, which was left under occlusion for 24 hours. After the 24 hours exposures, the sites were gently wiped with clean gauze to remove non-absorbed material. One animal died during the 15-day observation period on day 13. Consequently, LD50 was determined to be > 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Older, not optimally reported pre-GLP study similar to OECD 402 guidelines.

Additional information

Oral

There are four studies available for evaluation of N-Coco-1,3-diaminopropane CAS 61791-63-7 (recently redefined as Amines, N-C12-18-alkyltrimethylenedi-, CAS 68155-37-3), also referred to as Coco-diamine.

 

In the selected key study (BSL, 073803B, 2008), the toxic effects following an acute oral dose of N-Coco-1,3-diaminopropane was determined according to the guidelines for the acute toxic class method (OECD 423) performed under GLP.

In step 1 a single female rats were dosed by oral gavage with 2000 mg N-Coco-1,3-diaminopropane /kg bw in cotton seed oil. Within 1 h 30 min post-dose the animal was found dead. In step 2 three female rats were dosed with 300 mg/kg bw. All three animals showed severe signs of toxicity indicated by immediate piloerection followed by half eyelid closure, sunken flank, diarrhoea, bloody snout and mouth, weight loss and heavy breathing. All animals recovered between 2 and 7 days post-dosing. In step 3 three female rats were dosed with 300 mg/kg bw.

Again severe signs of toxicity were observed from wich one animal recovered from day 7, whereas to other two animals were found dead on day 3 and 5. In both step 4 and 5 three animals were dose 50 mg/kg bw. No compound related mortality was recorded for any of the animals.

According to GHS classification, the substance need to classified for acute oral toxicity into Category 3, with a LD50 cut-off of 300 mg/kg bw.

 

A next GLP study (SafePharm, CESIO, 1991) evaluated the acute oral toxicity of N-Coco-1,3-diaminopropane according to OECD 401. Following a preliminary study, the substance was administered to groups of 5 male and 5 female rats at dose levels of 250, 315, 397 and 500 mg/kg. Deaths were noted one to four hours after treatment and one to seven days I after treatment. One female treated with 315 mg/kg was found dead thirteen days after treatment and one male treated with 250 mg/kg was found dead twelve days after treatment. Major signs of toxicity noted were hunched posture, pilo-erection, lethargy, decreased respiratory rate, ataxia, ptosis, pal lor of the extremities, red/brown staining around the eyes, mouth and snout, with occasional or isoated signs of coma, distended abdomen, emaciation, tiptoe gait, gasping respiration, loss of righting reflex and increased salivation. There was no difference in mortality between males and females. The study concluded to an acute oral LD50 of 272 mg/kg bw, with a confidence interval of 222-333 mg/kg bw.

 

Another non-GLP study (Hoechst, 91.0919, 1991) also evaluated the acute oral toxicity of N-Coco-1,3-diaminopropane according to OECD 401.

Test substance was administered as a emulsion in deionised water to groups of 5 male and 5 female rats at levels of 200 and 315 mg/kg bw, At 315 mg/kg bw all animals died. At 200 none of the animals died. Consequently, LD50 was determined to be between 200 mg/kg bw (0% mortality) and 315 mg/kg (100% mortality).

 

A non-GLP study (F&D Res.Lab, SD-1684, 1981) evaluated the acute oral toxicity of N-Coco-1,3-diaminopropane according to similar principles as OECD 401. Validity is limited as reporting is limited and it involves a poor copy. The actually applied dose levels are not visible.

Following a preliminary study, the substance was administered to groups of 5 male and 5 female. The study concluded to an acute oral LD50 of 147.5 mg/kg bw, with a confidence interval of 136.3-161.1 mg/kg bw. To explain the somewhat lower LD50 value from this study compared to the other available data, it is possible that the substance was administered in a pure form, which would result to maximal corrosive properties in gastro-intestinal system.

 

Below an overview of the relevant information on acute oral toxicity available for the shorter chain diamines (C12, C12-14, C12-18 or Coco) showing consistent results.

Chain	Design	Study	Result
Coco	OECD 423	BSL, 073803B, 2008	LD50 cut-off of 300 mg/kg bw.
Coco	OECD 401	SafePharm, CESIO, 1991	LD50 = 272 mg/kg bw (c.i. 222-333)
Coco	OECD 401	Hoechst, 91.0919, 1991	LD50 200 - 315 mg/kg
Coco	OECD 401	F&D Res.Lab, SD-1684, 1981	LD50 = 147.5 mg/kg bw,(c.i. 136-161)
C12-14	OECD 423	BSL, 073803C, 2008	LD50 cut-off of 200 mg/kg bw.
C12	OECD 401	Hoechst, 93.0083, 1994	LD50 200 - 315 mg/kg

 

Inhalation:

There is no study on inhalation toxicity available for N-C12-18-alkyltrimethylenediamines.

REACH stipulates that testing by the inhalation route is appropriate if exposure of humans via inhalation is likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size. REACH guidance R.7.a, chapter. 7.4 Acute toxicity indicates that in principle no inhalation studies are needed when vp < 0.1 Pa at 20°C or particle size > 100 µm. Amines, N-C12-18-alkyltrimethylenedi-, is a liquid/paste with no inhalable particles and a vapour pressure of 0.0015 Pa at 20°C (value based on read-across from C_12-14-diamine showing almost similar average molecule weight). Also the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalation route will be unlikely to occur, and no acute inhalation test was performed.

 

N-C12,18-alkyl-1,3-diaminopropane is a liquid with pasty elements, and a melting point of 20°C is indicated. At ambient temperatures around 20°C and lower it is therefore no fluid and viscosity has therefore not been measured. No information on viscosity is available at 40°C, and hence the hazard for aspiration cannot be adequately assessed.

 

Dermal:

The acute dermal toxicity N-Coco-1,3-diaminopropane (N-C12-18-alkyltrimethylenediamines) was tested in New Zealand White Rabbits according to a study design similar to OECD 402 (F&D Res.Lab, SD-1684, 1981 - pre-GLP). The back and flanks of 5 male and 5 female rabbits were clipped, constituting about 30% of the total body surface. Just prior of the application test substance, the skin surface was abraded in 3 of the males and 2 of the females. The animals received 2000 mg/kg undiluted test material, which was left under occlusion for 24 hours. After the 24 hours exposures, the sites were gently wiped with clean gauze to remove non-absorbed material. One animal died during the 15-day observation period. Consequently, LD50 was determined to be > 2000 mg/kg bw. No information is provided on possible local effects, observed clinical effects or possible differences between the group with abrade and non-abraded skin.

Justification for classification or non-classification

Available studies result to GHS classification Category 3 for acute oral toxicity (LD50 between 50 and 300 mg/kg bw) based on LD50 cut-off of 300 mg/kg bw. Testing for dermal toxicity is not required in view of its corrosive properties, but information from acute dermal toxicity study is available, showing a low systemic toxicity following dermal application not requiring classification.

 

Related to low vp and no inhalable particles, there will be no exposures via inhalation.

No classification STOT-SE Cat.3 needed:

The active substance is not structurally related to any known class of neurotoxic chemicals. In addition, repeated dose studies did not show indications of specific neurotoxicity, in specific neurotoxicity measures as sensory activity, grip strength, and motor activity assessment.