Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

No acute toxicity studies have been performed using C12 -16 amine oxide. Data are read across from C12-14 and C12-18 AO on the basis of the large overlap in chain length distributions between the substances.
Acute oral toxicity: Two reliable studies are available for C12-18 AO and six for C12-14 AO, all performed on the commercial product as supplied. In all cases, the reported LD50 values (rat) are > 2000 mg/kg bw (based on test substance). In the key study [Rupprich N & Weigand W (1983)], the reported LD50 (rat, female) was 2820 mg/kg bw, equivalent to 846 mg AO/kg bw.
Acute dermal toxicity: Two reliable studies are available. In the key study performed using C12-18 alkyl dimethylamine oxide, the reported LD50 (rat) was > 2000 mg AO/kg bw [Haferkorn J (2010)].
Acute inhalation toxicity: No studies are available. The substance is a solid with very low vapour pressure. It is manufactured and supplied as an aqueous solution, therefore there is no possibility of exposure to dust. It is used in some spraying applications, but it is expected that inhalation exposure from these applications will be low and hence the dermal route is more relevant.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
27-09-1983 to 22-11-1983
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study.
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hoescht AG.
- Age at study initiation:
- Weight at study initiation: Males, mean = 202 g (191 - 219 g ); females, mean = 194 g (185 - 205 g)
- Fasting period before study: 16 h before and 2 h after application.
- Housing: Air-conditioned room in makrolon cages (type 4) on soft wood shavings in groups of 5 animals.
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2 ºC
- Humidity (%): 55 ± 10 %
- Photoperiod (hrs dark / hrs light): 12 h light/12 dark
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 25 % w/v

MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg
Doses:
1250, 2000, 2500, 3150, 4000 and 5000 mg/kg bw.
No. of animals per sex per dose:
5 females only for groups dosed at 1250, 2000 and 2500 mg/kg.
5/sex/dose for the group dosed at 3150 mg/kg.
5 males only for groups dosed at 4000 and 5000 mg/kg.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were weighed weekly
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs and body weight
Statistics:
The LD50, the 95 % confidence range and the calculation of the probit were determined directly from the death rates (Probit analysis by the method of Lindner and Weber; the confidence limits were calculated according Fieller or Sidak).
Preliminary study:
No data
Sex:
male
Dose descriptor:
LD50
Effect level:
4 120 mg/kg bw
Based on:
test mat.
95% CL:
3 400 - 5 010
Sex:
female
Dose descriptor:
LD50
Effect level:
2 820 mg/kg bw
Based on:
test mat.
95% CL:
2 360 - 3 540
Sex:
male
Dose descriptor:
LD50
Effect level:
1 236 mg/kg bw
Based on:
act. ingr.
Sex:
female
Dose descriptor:
LD50
Effect level:
846 mg/kg bw
Based on:
act. ingr.
Mortality:
There were deaths in the female rats at 2500 mg/kg (1/5) and at 2500 mg/L (4/5).
Deaths in male rats occurred at 4000 mg/kg (3/5) and 5000 mg/kg (4/5).
Animals died at 1 - 2 days post exposure.
Clinical signs:
other: After 10 minutes after treatment male animals were observed squatting or prone on their stomach or side and a narrowing of the lids. After 30 - 60 miniutes these symptoms were also observed in the females. 30 -60 minutes post application diarrhoea was ob
Gross pathology:
The necropsy of the male animals that died during the study showed the stomach and small intestine filled with yellowish-green liquid and partial whitening of the liver was observed. The necropsy of the dead females showed a reddish liquid-filling the gastrointestinal tract. In two animals the thorax was filled with pink liquid. Some animals showed autolytic changes. Surviving animals were free from visible macroscopic changes.
Other findings:
No data

Clinical signs observed in females:

Time after

application

From

0

min

10

min

30

min

1 h

2 h

4 h

1 d

2 d

3 d

4 d

To

10

min

30

min

60

min

2 h

4 h

6 h

14 d

1250 mg/kg bw: Females

Mortality

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

Number of animals with symptoms:

Ruffled fur

 

 

 

5

5

5

 

 

 

 

No symptoms

5

5

5

 

 

 

5

5

5

5

Necropsy:

5/5 no visible macroscopic abnormalities

2000 mg/kg bw: Females

Mortality

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

Number of animals with symptoms:

Squatting

 

 

2

2

2

2

 

 

 

 

Ruffled fur

 

 

 

5

5

5

 

 

 

 

Subdued

 

 

 

 

5

5

 

 

 

 

Diarrhoea

 

 

 

5

5

5

 

 

 

 

No symptoms

5

5

3

 

 

 

5

5

5

5

Necropsy:

5/5 no visible macroscopic abnormalities

2500 mg/kg bw: Females

Mortality

0/5

0/5

0/5

0/5

0/5

0/5

1/5

1/5

1/5

1/5

Number of animals with symptoms:

Squatting

 

2

3

5

3

5

 

 

 

 

Narrow palpebral fissures

 

3

4

5

5

5

 

 

 

 

Positioned on their belly or side

 

 

 

 

2

 

 

 

 

 

Belly and flanks drawn in

 

 

2

3

5

3

 

 

 

 

Ruffled fur

 

 

 

 

5

5

 

 

 

 

Diarrhoea

 

 

2

3

5

5

 

 

 

 

No symptoms

5

 

 

 

 

 

4

4

4

4

Necropsy:

1/5 gastrointestinal tract filled with yellow fluid

1/5 full bulging stomach

4/5 no visible macroscopic abnormalities

3150 mg/kg bw: Females

Mortality

0/5

0/5

0/5

0/5

0/5

1/5

4/5

4/5

4/5

4/5

Number of animals with symptoms:

Squatting

 

 

3

3

3

 

 

 

 

 

Ruffled fur

 

 

 

5

5

 

 

 

 

 

Positioned on their belly or side

 

 

 

2

2

3

 

 

 

 

Subdued

 

 

 

5

5

4

 

 

 

 

Decreased respiratory rate

 

 

 

 

2

4

 

 

 

 

Diarrhoea

 

5

5

5

5

5

 

 

 

 

No symptoms

5

 

 

 

 

 

1

1

1

1

Necropsy:

1/5 vessels of the gastrointestinal tract protruding

3/5 gastrointestinal tract filled with reddish fluid

2/5 thorax filled with pink fluid

1/5 gastrointestinal tract filled with yellow fluid

1/5 full bulging stomach

3/5 autolysis (advanced)

1/5 no visible macroscopic abnormalities

Clinical signs observed in males:

Time after

application

From

0

min

10

min

30

min

1 h

2 h

4 h

1 d

2 d

3 d

4 d

To

10

min

30

min

60

min

2 h

4 h

6 h

14 d

3150 mg/kg bw: Males

Mortality

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

Number of animals with symptoms:

Squatting

 

4

2

2

1

1

 

 

 

 

Belly and flanks drawn in

 

5

5

5

5

5

 

 

 

 

Subdued

 

5

5

5

5

5

 

 

 

 

Positioned on their belly or side

 

1

2

3

3

3

 

 

 

 

Decreased respiratory rate

 

 

1

3

3

3

 

 

 

 

Ruffled fur

 

 

5

5

5

5

 

 

 

 

High-legged position

 

 

 

2

2

2

 

 

 

 

Narrow palpebral fissures

 

 

 

4

5

5

 

 

 

 

Diarrhoea

 

 

 

5

5

5

 

 

 

 

No symptoms

5

 

 

 

 

 

5

5

5

5

Necropsy:

5/5 no visible macroscopic abnormalities

4000 mg/kg bw: Males

Mortality

0/5

0/5

0/5

0/5

0/5

0/5

3/5

3/5

3/5

3/5

Number of animals with symptoms:

Subdued

5

5

5

5

5

5

 

 

 

 

Narrow palpebral fissures

 

5

5

3

5

5

 

 

 

 

Belly and flanks drawn in

 

5

5

5

3

3

 

 

 

 

Creeping forward

 

5

5

5

3

3

 

 

 

 

Decreased respiration rate

 

 

2

2

3

3

 

 

 

 

Eyelids closed

 

 

2

2

2

2

 

 

 

 

Supine position

 

 

1

1

 

 

 

 

 

 

Squatting

 

 

 

 

2

2

 

 

 

 

Diarrhoea

 

 

3

5

5

5

 

 

 

 

Strong noisy breathing

 

 

 

 

 

 

 

 

2

 

No symptoms

 

 

 

 

 

 

2

2

 

2

Necropsy:

2/5 liver partially lightened

1/5 full bulging stomach

3/5 small intestine filled with yellowish-green liquid

3/5 autolysis (early stages)

2/5 no visible macroscopic abnormalities

5000 mg/kg bw: Males

Mortality

0/5

0/5

0/5

0/5

0/5

0/5

2/5

4/5

4/5

4/5

Number of animals with symptoms:

 

 

 

 

 

 

 

 

 

 

Squatting

 

 

 

 

 

 

 

 

 

 

Belly and flanks drawn in

 

 

 

 

 

 

 

 

 

 

Subdued

 

 

 

 

 

 

 

 

 

 

Supine position

 

 

 

 

 

 

 

 

 

 

Eyelids closed

 

 

 

 

 

 

 

 

 

 

Creeping forward

 

 

 

 

 

 

 

 

 

 

Diarrhoea

 

 

 

 

 

 

 

 

 

 

Ruffled fur

 

 

 

 

 

 

 

 

 

 

Noisy breathing

 

 

 

 

 

 

 

 

 

 

No symptoms

 

 

 

 

 

 

 

 

 

 

Necropsy:

4/5 liver lightened

4/5 bulging translucent stomach

4/5 small intestine filled with yellowish green liquid

2/5 autolysis (early stages)

1/5 no visible macroscopic abnormalities

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral toxicity of the test substance was assessed in male and female rats according to OECD guideline 401 and EU method B.1. The acute oral LD50 of the test substance in males rats was 4120 mg/kg bw with 95 % confidence limits of 3400 - 5010 mg/kg bw. The acute oral LD50 of the test substance in female rats was 2820 mg/kg with 95 % confidence limits of 2360 - 3540 mg/kg bw.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
846 mg/kg bw
Quality of whole database:
There are 8 acute oral toxicity studies performed on either C12-14 or C12-18 AO. One study is Klimisch score 1 and the remainder are Klimisch score 2.

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:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
21/12/2009 - 19/02/2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study conducted according to GLP;
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: CD/Crl: CD(SD)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services Germany GmbH
- Age at study initiation: males 7 weeks; females 9 weeks
- Weight at study initiation: males 221-235 g; females 206-224 g
- Fasting period before study: 16 hours
- Housing: Housed singly during the 14 day observation period in Makrolon cages
- Diet (e.g. ad libitum): ssniff R/M-H V1534
- Water (e.g. ad libitum): ad libitum
- Acclimation period:at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 55 +/- 15
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To: 7/01/2010 - 3/02/2010
Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: animals back, 5x6 cm
- % coverage: approx 10 % of body surface
- Type of wrap if used: 8 layers of gauze covered with a plastic sheet and secured with adhesive plaster

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not applicable
- Time after start of exposure: not applicable

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 mL/kg bw
- Concentration (if solution): not stated
- Constant volume or concentration used: yes

Duration of exposure:
24 hours
Doses:
2000 mg AO/kg bw
No. of animals per sex per dose:
5 animals/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations before and immediately, 5, 15, 30 and 60 min, as well as 3, 6 and 24 hours after administration. During the 14 day observation period observed at least once daily until all symptoms subsided and daily thereafter. Bodyweight recorded before administration and thereafter in weekly intervals up to the end of the study
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Preliminary study:
No preliminary study performed
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
act. ingr.
Mortality:
No deaths seen during the study
Clinical signs:
other: No clinical signs seen during the study
Gross pathology:
No macroscopic changes were noted at necropsy
Other findings:
- Other observations: Erythema (grade 2-4) was observed at the application site in all 5 males and 5 females immediately after patch removal until test day 6 No oedema was observed in any animals. All reactions cleared by Day 7.

Table 1: Skin reactions observed during the study

Animal No. & sex

Skin reactions on test day

 

1

2

3

4

5

6

7

 

 

E/Oe/N

E/Oe/N

E/Oe/N

E/Oe/N

E/Oe/N

E/Oe/N

1 m

 

2/0/0

2/0/0

3/0/0

4/0/0

4/0/0

0/0/0

2 m

 

2/0/0

2/0/0

3/0/0

4/0/0

4/0/0

0/0/0

3 m

 

2/0/0

0/0/0

3/0/0

4/0/0

4/0/0

0/0/0

4 m

 

2/0/0

2/0/0

3/0/0

4/0/0

4/0/0

0/0/0

5 m

 

2/0/0

2/0/0

3/0/0

4/0/0

4/0/0

0/0/0

6 f

 

2/0/0

2/0/0

3/0/0

4/0/0

4/0/0

0/0/0

7 f

 

2/0/0

2/0/0

3/0/0

4/0/0

4/0/0

0/0/0

8 f

 

2/0/0

2/0/0

3/0/0

4/0/0

4/0/0

0/0/0

9 f

 

2/0/0

2/0/0

3/0/0

4/0/0

4/0/0

0/0/0

10 f

 

2/0/0

2/0/0

3/0/0

4/0/0

4/0/0

0/0/0

Animal No. & sex

Skin reactions on test day

 

8

9

10

11

12

13

14

 

 

E/Oe/N

E/Oe/N

E/Oe/N

E/Oe/N

E/Oe/N

E/Oe/N

1 m

0/0/0

0/0/0

0/0/0

0/0/0

0/0/0

0/0/0

0/0/0

2 m

0/0/0

0/0/0

0/0/0

0/0/0

0/0/0

0/0/0

0/0/0

3 m

0/0/0

0/0/0

0/0/0

0/0/0

0/0/0

0/0/0

0/0/0

4 m

0/0/0

0/0/0

0/0/0

0/0/0

0/0/0

0/0/0

0/0/0

5 m

0/0/0

0/0/0

0/0/0

0/0/0

0/0/0

0/0/0

0/0/0

6 f

0/0/0

0/0/0

0/0/0

0/0/0

0/0/0

0/0/0

0/0/0

7 f

0/0/0

0/0/0

0/0/0

0/0/0

0/0/0

0/0/0

0/0/0

8 f

0/0/0

0/0/0

0/0/0

0/0/0

0/0/0

0/0/0

0/0/0

9 f

0/0/0

0/0/0

0/0/0

0/0/0

0/0/0

0/0/0

0/0/0

10 f

0/0/0

0/0/0

0/0/0

0/0/0

0/0/0

0/0/0

0/0/0

m = male         E = erythema   N = necrosis

f = female         Oe = Oedema   0 = no pathological findings

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 of C12-18 amine oxide is > 2000 mg AO/kg bw
Executive summary:

The acute dermal toxicity of the substance was investigated in a GLP study performed to OECD 402. The substance was applied as a solution in water to the skin of 5 male and 5 female rats (CD/Crl: CD(SD)) at a dose of 2000 mg AO/kg bw and covered with an occlusive dressing for 24 hours. After completion of the exposure period the dressing was removed. There were no deaths or signs of systemic toxicity during the 14 -day observation period and animals showed the expected bodyweight gains. Erythema (grade 2-4) was observed at the application site in all 5 males and 5 females immediately after patch removal until test day 6. No Oedema was noted at any time period. All reactions cleared after 7 days. Necropsy revealed no macroscopic findings. The LD50 was 2000 mg AO/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
Both studies were performed to OECD guidlines and in addition, the selected study was performed undet GLP and has a Klimisch score of 1.

Additional information

No acute toxicity studies have been performed using C12 -16 amine oxide. Data are read across from C12-14 and C12-18 AO on the basis of the large overlap in chain length distributions between the substances.

Acute oral toxicity:

Two reliable studies are available for C12-18 AO and six for C12-14 AO. All the studies have been performed with commercial grades of amine oxide (AO) as supplied (normally an approximately 30 % aqueous solution).

In the key study [Rupprich N & Weigand W (1983) ] performed according to OECD TG 401 groups of rats (Wistar) were dosed by gavage withC12-18 AOat 1250, 2000, 2500 or 3150 mg test material/kg bw (females, 5/group) or 3150, 4000 or 5000 mg test material/kg bw (males, 5/group) (equivalent to 375, 600, 750 or 945 mg AO/kg bw for females and 945, 1200 or 1500 mg AO/kg bw for males). One female died in the 2500 mg/kg bw group and 4 died in the 3150 mg/kg bw group, whilst 3 males died in the 4000 mg/kg bw group and 4 in the 5000 mg/kg bw group. Signs of toxicity included ruffled fur in all groups, diarrhoea, squatting and subdued behaviour at doses of 2000 mg/kg bw and higher, narrow palpebral fissures from 2500 m/kg bw. Necropsy revealed no visible macroscopic findings in 1250 or 2000 mg/kg bw females. At higher doses findings included gastrointestinal tract filled with yellow fluid & full bulging stomach (2500 mg/kg bw) protruding gastrointestinal tract vessels, tract filled with reddish or yellow fluid, thorax filled with pink fluid, full bulging stomach, autolysis (advanced) (3150 mg/kg bw females). There were no visible macroscopic abnormalities in the 3150 mg/kg bw males. Findings at higher doses included full bulging stomach, small intestine filled with yellowish-green liquid, autolysis (early stages) and liver lightened. The LD50 was 2820 mg/kg bw, equivalent to 846 mg AO/kg bw for females and 4120 mg/kg bw, equivalent to 1236 mg AO/kg bw for males.

In a study using C12-14 AO [Fulfs JC (1978a) ] performed according to OECD TG 401, groups of rats (Sprague-Dawley, 5 animals/sex/dose) were dosed by gavage at 1500, 2100, 3000, 4100 or 5800 mg test material/kg bw (equivalent to 420, 588, 840, 1148 or 1624 mg AO/kg bw). There were no deaths at the lowest dose. Two females died at 2100 mg/kg bw, one male died at 3000 mg/kg bw, two males and four females died at 4100 mg/kg bw and five males and four females died at 5800 mg/kg bw. The gross toxic signs observed included decreased motor activity and salivation in all five test groups. Piloerection was observed in the 4100 and 5800 mg/kg bw dose groups. Blanching and nasal haemorrhaging were observed in the 2100, 3000, 4100 and 5800 mg/kg dose groups. Diarrhoea was observed in the 1500, 3000, 4100 and 5800 mg/kg dose groups. Bodyweight gain was seen in all dose groups except for the high dose group where a slight loss was observed. Necropsy revealed no remarkable observations at the low dose. At higher doses findings included tan discolouration, pale lungs, gas and fluid in stomach and intestines (2100 mg/kg bw), gas and fluid in stomach and intestines, petachiae on lungs (3000 mg/kg bw), tan discolouration on lungs, fluid filled stomach and intestines, bright red lungs, yellow fluid in small intestines (4100 mg/kg bw) and liver coloured lungs, fluid filled stomach and small intestines, tan discolouration and petachiae on lungs and gas in stomach (5800 mg/kg bw). The LD50 was 3800 mg/kg bw, equivalent to 1064 mg AO/kg bw.

Jones JR et al (1986) dosed rats (Sprague-Dawley, 5 animals/sex) by gavage with 2000 mg/kg bw of a 30 % solution of C12 -14 AO in a limit test performed according to OECD TG 401 under GLP. There were no deaths during the study. All the animals showed hunched posture and piloerection one and four hours after treatment. All animals recovered and appeared normal on day 1 and for the rest of the study period. All animals showed normal gains in bodyweight. Abnormalities noted at necropsy were scattered white raised areas covering approximately 25 % of the non-glandular region of the stomach. No other abnormalities were noted. Based on these results the LD50 was > 2000 mg/kg bw, equivalent to > 600 mg AO/kg bw.

Hofmann T (1987) also dosed rats (Wistar, 5 animals/sex) by gavage with 2000 mg/kg bw of a 30 % solution of C12 -14 AO in a limit test performed according to OECD TG 401 under GLP. There were no deaths or clinical signs noted during the study period. Bodyweight gains were not impaired and there were no macroscopically visible changes noted at necropsy. Based on these results the LD50 was > 2000 mg/kg bw, equivalent to > 600 mg AO/kg bw. In the three further studies, 5600 mg/kg bw (equivalent to 1680 mg AO/kg bw) [Bullens P (1984a) ], >2000 mg/kg bw (equivalent to > 600 mg AO/kg bw) [Gunn J & Goodwin M (1983) ] and >5000 mg/kg bw (equivalent to >300 mg AO/kg bw) [Gill CRB (1977) ].

Acute dermal toxicity:

Two studies are available. The key study [Haferkorn J (2010) ] was performed using C12 -18 AO. In this study, performed according to OECD TG 402 under GLP the test substance was applied as a solution in water to the skin of 5 male and 5 female rats (CD/Crl: CD(SD)) at a dose of 2000 mg AO/kg bw and covered with an occlusive dressing for 24 hours. After completion of the exposure period the dressing was removed. There were no deaths or signs of systemic toxicity during the 14 -day observation period and animals showed the expected bodyweight gains. Erythema (grade 2-4) was observed at the application site in all 5 males and 5 females immediately after patch removal until test day 6. No Oedema was observed in any animal at any time period. Erythema was not observed from day 7 onwards (Grade = 0). Necropsy revealed no macroscopic findings. The LD50 was > 2000 mg AO/kg bw.

In the second study, performed according to OECD TG 402 [Dean WP (1978a) ] C12-14 AO was applied as a solution in water to the skin of 3 male and 3 female rabbits (New Zealand White) at a dose of 2000 mg/kg bw (equivalent to 560 mg AO/kg bw) and covered with an occlusive dressing for 24 hours. One rabbit died during the observation period. This death was attributed to pneumonia and was not considered to be related to treatment. One female rabbit showed hypoactivity, decreased limb tone ataxia and anorexia. Surviving animals showed expected bodyweight gains. Necropsy revealed pale green fluid and white mucoid material adhering to mucosa in the stomach, severe congestion, consolidation and white film adhering in the lungs of the animal that died of pneumonia. In the surviving animals no gross lesions were noted except mottled colouration in the kidneys of one male. The LD50 >2000 mg/kg bw (equivalent to > 560 mg AO/kg bw).

Acute inhalation toxicity:

No data are available for the inhalation route. The substance is a solid with very low vapour pressure. It is manufactured and supplied as an aqueous solution therefore there is no possibility of exposure to dust. It is used in some spraying applications, but it is expected that inhalation exposure from these applications will be low and hence the dermal route is more relevant.


Justification for selection of acute toxicity – oral endpoint
All the available acute oral toxicity studies were performed on products containing approximately 30 %w/w/ AO. Rupprich N & Weigand W (1983) was selected because it is a guideline study performed under GLP and gave the lowest absolute value for the LD50.

Justification for selection of acute toxicity – inhalation endpoint
The substance is a solid with very low vapour pressure. It is used in some spraying applications, but it is expected that inhalation exposure from these applications will be low. The most likely route of exposure for consumers and professionals is the dermal route. Testing for acute toxicity via the inhalation route is, therefore, not required.

Justification for selection of acute toxicity – dermal endpoint
Both acute dermal toxicity studies were performed on commercial grades of amine oxides, typically containing approximately 30 % AO in aqueous solution. The study performed using C12-18 AO was selected because it was performed at a sufficiently high dose level to allow the discriminating dose to be elucidated.

Justification for classification or non-classification

No acute toxicity studies have been performed using C12 -16 amine oxide. Data are read across from C12-14 and C12-18 AO on the basis of the large overlap in chain length distributions between the substances and used to determine the classification and labelling of C12-16 amine oxide.

Acute oral toxicity: All studies were performed using commercial grades of the substance (normally an approximately 30 % aqueous solution of the amine oxide). In all cases, the LD50 of the test substance was > 2000 mg/kg bw, indicating that the commercial product as supplied should not be classified. Taking into account the concentration of amine oxide present in the solution, the lowest LD50 is derived from the OECD TG 401 study using C12-18 AO performed by Rupprich N & Weigand W (1983), where LD50 (females) = 846 mg AO/kg bw. Based on this result the classification of the pure amine oxide is Acute Toxicity 4, with the Hazard Statement H302: Harmful if swallowed.

Acute dermal toxicity: An OECD TG 402 study performed using C12 -18 AO resulted in a LD50 > 2000 mg AO/kg bw [Haferkorn J (2010)]. This is supported by a limit test performed with C12-14 AO which resulted in a LD50 > 560 mg AO/kg bw [Dean WP (1978a)]. On the basis of these two studies classification for acute dermal toxicity is not required.

Acute inhalation toxicity: No data are available. Testing was not performed as the dermal route was considered to be the most likely route of exposure.