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Administrative data

Description of key information

Acute oral toxicity: Six reliable studies are available, 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 [Fulfs JC (1978)], the reported LD50 (rat) was 3800 mg/kg bw, equivalent to 1064 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:
experimental study
Adequacy of study:
key study
Study period:
1977-11-18 - 1977-12-01
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study meets OECD Guidelines 401. Non-GLP
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
no
Remarks:
Pre-GLP
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Ind.
- Age at study initiation: Not available
- Weight at study initiation: Male- 211 - 264 gm and Female- 190 - 232 gm
- Fasting period before study: 18-20 hours
- Housing: Individually housed in stainless steel cages with stainless steel grid flooring
- Diet (e.g. ad libitum): Purina Rat Chow manufactured by the Ralston Purina Co.
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: Minimum 4 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.7 - 22.8 °C
- Humidity (%): 46 - 63%
- Air changes (per hr): Not available
- Photoperiod (hrs dark / hrs light): 12 hours on/off fluorescent lighting


IN-LIFE DATES: From: 1977-11-18 To: 1977-12-01
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: Not applicable
- Amount of vehicle (if gavage): Not applicable
- Justification for choice of vehicle: Not applicable
- Lot/batch no. (if required): Not applicable
- Purity: Not applicable


MAXIMUM DOSE VOLUME APPLIED: 1.4 ml


DOSAGE PREPARATION (if unusual): None


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: None
Doses:
1500, 2100, 3000, 4100, and 5800 mg P7270/kg bw which is equivalent to 420, 588, 840, 1148, and 1624 mg DDAO/kg BW
No. of animals per sex per dose:
5 males and 5 females per dose level
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observation was done at 1/4, 1/2, 1, 2 and 4 hours post-administration and daily thereafter for 14 days. Prefasted body weight was taken and on 14th day.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, mortality and gross pathology
Statistics:
LD50 was calculated using the computer program BLISS 17 (D. J. Finney)
Preliminary study:
Not applicable
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 800 mg/kg bw
Based on:
test mat.
95% CL:
3 100 - 4 800
Remarks on result:
other: aqueous solution as manufactured and supplied containing 28 %w/w AO
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 064 mg/kg bw
Based on:
act. ingr.
95% CL:
868 - 1 344
Mortality:
0/5 males and 0/5 females at 1500 mg/kg
0/5 males and 2/5 females at 2100 mg/kg
1/5 males and 0/5 females at 3000 mg/kg
2/5 males and 4/5 females at 4100 mg/kg
5/5 males and 4/5 females at 5800 mg/kg
Clinical signs:
The gross toxic signs observed included decreased motor activity and salivation in all five test groups. Pilo erection was observed in the 4100 and 5800 mg/kg dose groups. Blanching and nasal hemorrhaging were observed in the 2100, 3000, 4100 and 5800 mg/kg dose groups. Diarrhea was observed in the 1500, 3000, 4100 and 5800 mg/kg dose groups.
Body weight:
Body weight gain was seen in surviving animals at all the dose levels except slight loss in body weight was seen at 5800 mg/kg dose level.
Gross pathology:
1500 mg/kg (male/female): Not remarkable observation
2100 mg/kg (male): Tan discoloration and pale lungs
(female): Gas and fluid in stomach and intestines
3000 mg/kg (males): Gas and fluid in stomach and intestines
(females): Petechiae on lungs
4100 mg/kg (males): Tan discoloration on lungs, fluid filled stomach and intestines, bright red lungs.
(females): Fluid in stomach, yellow fluid in small intestine, Gas and fluid in stomach and intestine, Fluid filled stomach and intestines and Tan discoloration on lungs.
5800 mg/kg (males): Liver- colored lungs, fluid filled stomach and small intestines, Tan discoloration and petechiae on lungs.
(females): Liver- colored lungs, fluid filled stomach and small intestines, Tan discoloration and petechiae on lungs, gas and fluid in
stomach.
Other findings:
- Organ weights: None
- Histopathology: None
- Potential target organs: None
- Other observations: None

None

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The LD50 of P7270 is 3800 mg/kg which is equivalent to 1064 mg AO/kg on an active DDAO level. Therefore this test material is classified under OECD GHS Toxicity Category IV.
Executive summary:

The LD50 of dodecyl dimethyl amine oxide is 1064 mg/kg bw based on an active substance level (3800 mg/kg nominal as P7270). Therefore it was concluded that this test substance belongs to OECD GHS Toxicity Category IV.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
1 064 mg/kg bw
Quality of whole database:
Six reliable studies are available.

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 from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
21/12/2009 - 19/02/2010
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study conducted according to GLP;
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: CD/Crl: CD(SD)
Sex:
male/female
Details on test animals 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:
No clinical signs seen during the study
Body weight:
All animals gained the expected weight throughout the experimental period
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
2 000 mg/kg bw
Quality of whole database:
Two reliable studies are available.

Additional information

Acute oral toxicity:

Six reliable studies are available. All the studies have been performed with commercial grades of C12 -14 amine oxide (AO) as supplied (normally an approximately 30 % aqueous solution). In the key study [Fulfs JC (1978)] 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 (1984)], >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 alkyl dimethylamine oxide. 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)] the substance 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
Study chosen because it gives the lowest definitive LD50 value

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

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 by Fulfs JC (1978), where LD50 = 1064 mg AO/kg bw. This results in classification of the pure amine oxide as Acute Toxicity 4, with the Hazard Statement H302: Harmful if swallowed.

Acute dermal toxicity: An OECD TG 402 study performed using C12 -18 alkyl dimethylamine oxide resulted in a LD50 > 2000 mg AO/kg bw [Haferkorn J (2010)]. This is supported by a limit test performed with the substance 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.