Dodecyldimethylamine oxide

Endpoint summary

Description of key information

Acute oral toxicity: No studies are available on C12 AO. However, studies are available for C12-14 AO, where C12 AO makes up 60-80 % of the substance. Read across to the key study [Fulfs JC (1978)] gives an LD50 value of 1064 mg/kg bw.

Acute dermal toxicity: No studies are available for C12 AO. Studies are available for C10 AO [Haferkorn j (2012b)], C12-14 AO [Dean WP (1978)] and C12-18 AO [Haferkorn J (2010)] and these are used in a weight of evidence approach since the range of chain lengths covers the C12 AO. On this basis, the LD50 is > 2000 mg/kg bw.

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

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

Date started 1986-11-07; Date completed 1986-12-03

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

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, Cambridgeshire
- Age at study initiation: 5-8 weeks at start of main study
- Weight at study initiation: Males 126-137 g; Females 123-138 g at start of main study
- Fasting period: In the main study, overnight immediately before dosing and for approximately two hours after dosing
- Housing: Solid floor polypropylene cages with sawdust bedding
- Diet: Free access to Rat and Mouse Expanded Diet No. 1, Special Diet Services Limited, Witham, Essex, U.K.
- Water: Free access to mains drinking water
- Acclimation period: Minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23
- Humidity (%): 45-65
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark controlled by a time switch

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Range-finding study

In order to establish a suitable dose level for the main study a group of two rats (one male and one female) was treated once only. Animals were observed 1 and 4 hours after dosing and then daily for five days.

Main study

All animals were dosed once only by gavage using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing. Animals were observed 1 and 4 hours after dosing and subsequently once daily for 14 days. Deaths and evidence of overt toxicity were recorded at each observation.

Doses:

See below

No. of animals per sex per dose:

Range-finding study: 1 male and 1 female

Main study: 5 male and 5 female

Control animals:

no

Details on study design:

The test material was used as supplied. The specific gravity as given by the study sponsor was used to calculate the appropriate dose volumes for the required dose levels. The identity and stability of the test material were not determined.

The animals were selected at random and given a unique number within the study by ear punching and a number written on a cage card.

Range-finding study

Individual bodyweights were recorded on the day of dosing to allow calculation of individual treatment volumes. No necropsies were performed.

Main study

Individual bodyweights were recorded on the day of treatment (day 0) and on days 7 and 14. All animals were subjected to gross necropsy examination for any macroscopic abnormalities. No tissues were retained.

Statistics:

Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test material was made. Clinical observations, bodyweights and necropsy records were examined for any adverse but non-lethal effects resulting from treatment.

Preliminary study:

Using the mortality data from the range-finding study (see below), the oral LD50 of the test material was considered to be greater than 2000 mg/kg. This dose level was therefore used for the main study.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: aqueous solution as manufactured and supplied containing 30 %w/w AO

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 600 mg/kg bw

Based on:

act. ingr.

Mortality:

No animals died during the range-finding study or the main study (see tables below)

Clinical signs:

other: All treated animlas showed hunched posture and pilo-erection one and four hours after treatment in the main study. All animals recovered and appeared normal on day one and for the rest of the study period. Individual clinical observations are given in Tab

Gross pathology:

Abnormalities noted at necropsy of animals killed at the end of the main study were scattered white raised areas covering approximately 25% of the non-glandular region of the stomach. No other abnormalities were noted. Individual necropsy findings are given in Table 3 (attached).

Other findings:

No data

Mortality data for the range-finding study

Dose Level Mg/kg	Sex	Deaths on Day						Total Deaths
		0	1	2	3	4	5
2000	Male	0	0	0	0	0	0	0/2
	Female	0	0	0	0	0	0

Mortality data for main study

Dose Level m/kg	Sex	Deaths on Day								Total Deaths
		1	2	3	4	5	6	7	8-14
2000	Male	0	0	0	0	0	0	0	0	0/10
	Female	0	0	0	0	0	0	0	0

Conclusions:

The acute oral median lethal dose (LD50) of the test material, AROMOX DMMCD-W, to the rat was found to be > 2000 mg/kg bodyweight. This result equates to an LD50 of > 600 mg/kg bodyweight based on active ingredient.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1987-07-16 to 1987-07-30

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hoechst AG, Kastengrund SPF breeding colony
- Age at study initiation: 6-10 weeks
- Weight at study initiation: 164.0- 173.0 g (males); 162.0-172.0 g (females)
- Fasting period: From about 16 hours before to 3-4 hours after treatment
- Housing: In fully air-conditioned rooms in macrolon cages (type 4) on soft wood granulate in groups of 5 animals
- Diet: Altromin 1324 ad libitum
- Water: Tap water in plastic bottles ad libitum
- Acclimation period: At least seven days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 50 ± 20
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12 hours daily

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

The observation period following treatment lasted for 14 days.

Doses:

The animlas received the compound as a 20% solution in water, the administration volume being 10 mL/kg body weight

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

The observation period following treatment lasted 14 days. Symptoms were recorded twice every day (in the morning and in the afternoon), on weekends and public holidays only once. During this time the animals were weighed weekly. At the end of the observation period the animals were killed by carbon dioxide asphyxiation, dissected and examined for macroscopically visible changes.

Statistics:

No data

Preliminary study:

No data

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: aqueous solution as manufactured and supplied containing 30 %w/w AO

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 600 mg/kg bw

Based on:

act. ingr.

Mortality:

No deaths occurred during the study

Clinical signs:

other: No clinical symptoms were observed after administration of 2000 mg/kg body weight

Gross pathology:

The animals killed at the end of the observation period showed no macroscopically visible changes

Conclusions:

Acute oral toxicity testing of Genaminox LA in the rat yielded a median lethal dose (LD50) above 2000 mg/kg body weight in both male and female animals. This result equates to an LD50 of 600 mg/kg bodyweight based on active ingredient.

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

No data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

according to guideline

Guideline:

other: No data

Deviations:

not specified

Principles of method if other than guideline:

The acute oral LD50 in rats was determined using 10 rats (5/sex/group) administered a single oral dose followed by a 14-day observation period.

GLP compliance:

no

Remarks:

Study pre-dates GLP.

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

other: The test material was administered in the form supplied for hte highest dose group; all others were diluted with water.

Doses:

15, 5, 0.5, 0.05 and 0.01 g/kg; followed by two further groups dosed at 15.1 and 5.1 g/kg.

No. of animals per sex per dose:

Five rats/sex/group in the definitive test; one rat/sex/group in the pilot study.

Control animals:

no

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: aqueous solution as manufactured and supplied containing 6 %w/w AO

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 300 mg/kg bw

Based on:

act. ingr.

Conclusions:

The 14-day acute oral toxicity LD50 of the test substance in the rat was in excess of 5.0 g/kg bw and would be classed as practically nontoxic according to the toxicity classes of Hodge and Sterner, 1943. There were no deaths or any overt signs of toxicity during the 14-day observation period at this dose. At 15 .1 g/kg bw all ten rats were lethargic within 4 h of treatment. Two/sex died 24 h after treatment and a further 2 male and 1 female rats died 48 h after treatment. The remaining three rats survived the 14 day test period and showed no overt signs of toxicity from Day 3 onwards.

Reference 4

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

10-05-1983 to 24-10-1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Qualifier:

according to guideline

Guideline:

other: No data

Deviations:

not specified

Principles of method if other than guideline:

The acute toxicity of the test material over a 14 day period was assessed through administration of a single oral dose to 10 rats (5/sex). The dose was determined by an initial range-finding study.

GLP compliance:

no

Remarks:

Study pre-dates GLP.

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

water

Doses:

25, 200 and 2000 mg/kg bw

No. of animals per sex per dose:

5/sex/group

Control animals:

no

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: aqueous solution as manufactured and supplied containing 30 %w/w AO

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 600 mg/kg bw

Based on:

act. ingr.

Conclusions:

The 14 day acute oral LD50 of the test substance was > 2000 mg/kg bw (equivalent to >600 mg AO/L), the maximum dose tested in this study. There were no deaths and no overt signs of toxicity.

Reference 5

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:

guideline study with acceptable restrictions

Qualifier:

according to guideline

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 or test system 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:

other: 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/

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

Conclusions:

The LD50 of P7270 is 3800 mg/kg which is equivalent to 1064 mg AO/kg. Therefore this test material is classified under OECD GHS Toxicity Category IV.

Executive summary:

The LD50 of dodecyl dimethyl amine oxide is 1064 mg AO/kg bw (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

Value:

1 064 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

24 May - 01 August 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

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, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: Approximately 8 weeks old
- Weight at study initiation: males 250-262 g; females 208-223 g
- Fasting period before study: 16 h
- Housing: During the 14-day observation period the animals were kept singly in MAKROLON cages (type III plus).
- Diet: Commercial diet, ssniff® R/M-H V1534 (ssniff Spezialdiäten GmbH, 59494 Soest, Germany served as food ad libitum. Feeding was discontinued approx. 16 hours before administration
- Water: Drinking water in bottles was offered ad libitum.
- Acclimation period: At least 5 adaptation days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 15
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12h/12h

IN-LIFE DATES: From: To: 01 June 2012-26 June 2012

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 5cmx6cm
- % coverage: approximately 10%
- 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): 5.08 mL/kg bw
- Concentration (if solution): 40.5 % w/w
- Constant volume or concentration used: not applicable
- For solids, paste formed: not applicable

VEHICLE
- Amount(s) applied (volume or weight with unit): Test material supplied as aqueous solution
- Concentration (if solution): 40.5 %w/w
- Lot/batch no. (if required): not applicable
- Purity: not applicable

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 were performed before and immediately, 5, 15, 30 and 60 min, as well as 3, 6 and 24 hours after administration. All animals were observed daily for a period of 14 days. Individual body weights were recorded before administration of the test item and thereafter in weekly intervals up to the end of the study. Changes in weight were calculated and recorded.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, skin reactions

Statistics:

not applicable

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr.

Mortality:

No deaths during the study

Clinical signs:

other: No clinicals signs of toxicity

Gross pathology:

No macroscopic findings were observed at necropsy

Other findings:

skin reactions - no skin reactions were seen in any of the animals

TABLE 1: Summarised results

 

Symptoms/ Criteria	N,N-dimethyldecylamine-N-oxide 2000 mg/kg b.w. (n=5)
	Males	Females
Clinical signs	None	None
Skin reactions	None	None
Mortality Within 6h Within 24 h Within 7d Within 14 d	0 0 0 0	0 0 0 0
Mean body weight (g) Start After 7 days After 14 days	255.4 317.4 (+24.3 %) 370 (+44.9 %)	216.4 235.4 (+8.8 %) 256.0 (+18.3 %)
Inhibition of body weight gain	None	None
Necropsy findings	None	None

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute dermal LD50 is > 2000 mg AO/kg bw

Executive summary:

Test Guideline

OECD Guideline 402 and EC Method B3

Method and material

C10 AO was applied to the shaved backs of CD rats (5 male/5 female) at a dose of 2000 mg AO/kg bw. An occlusive bandage was applied and the rats exposed for a period of 24 hours. After exposure the bandage was removed and the rats observed for 14 days for mortality, clinical signs and skin reactions. At the end of the study all animals were necropsied and examined macroscopically.

Results

There were no deaths and no clinical signs of toxicity. No skin reactions were observed in any of the animals and there were no macroscopic findings at necropsy. Bodyweight gain was normal.

The acute dermal LD50 is > 2000 mg AO/kg bw.

Conclusion

In accordance with CLP Regulation (EC) No 1272/2008 the substance is not classified for acute dernal toxicity.

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

21/12/2009 - 19/02/2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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.

Reference 3

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1978-03-10

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

3 males and 3 female were dosed instead of 5 males and 5 females

Principles of method if other than guideline:

Not applicable

GLP compliance:

no

Remarks:

Pre-GLP

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: Kuiper's Rabbit Ranch, Gary, Indiana
- Age at study initiation: Not available
- Weight at study initiation: 2310 - 2810 gm
- Fasting period before study: Not available
- Housing: Individually housed in hanging wire-mesh cages in temperature and humidity controlled quarters
- Diet (e.g. ad libitum): Purina Rabbit Chow, ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): In accordance with the recommendations contained in H.E.W. Publication No. 74-23 (N.I.H.)
- Humidity (%): In accordance with the recommendations contained in H.E.W. Publication No. 74-23 (N.I.H.)
- Air changes (per hr): In accordance with the recommendations contained in H.E.W. Publication No. 74-23 (N.I.H.)
- Photoperiod (hrs dark / hrs light): In accordance with the recommendations contained in H.E.W. Publication No. 74-23 (N.I.H.)


IN-LIFE DATES: Not available

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Back of the animal
- % coverage: 20-30%
- Type of wrap if used: The application site was covered with 8-ply gauze bandaging, rubber dam and several wrappings of 75 mm Elastoplast tape


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Backs were wiped with a wet disposable paper towel
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2 ml/kg
- Concentration (if solution): Undiluted
- Constant volume or concentration used: yes
- For solids, paste formed: Not applicable


VEHICLE
- Amount(s) applied (volume or weight with unit): Not applicable
- Concentration (if solution): Not applicable
- Lot/batch no. (if required): Not applicable
- Purity: Not applicable

Duration of exposure:

24 hours

Doses:

2000 mg P7270/kg bw (male/female) which is equivalent to 560 mg active dodecyl dimethyl amine oxide/kg bw

No. of animals per sex per dose:

3 males and 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations were done at 24 hours and daily thereafter for a total of 14 days. Initial, 7th day and 14th day body weights were taken
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, mortality and gross pathology

Statistics:

None

Preliminary study:

Not applicable

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: aqueous solution as manufactured and supplied containing 28 %w/w AO

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 560 mg/kg bw

Based on:

act. ingr.

Mortality:

1/6 rabbits died during the observation period. This death was attributed to pneumonia and was not considered to be compound related.

Clinical signs:

other: Males: 1-14 days: 3/3 animals appeared to be normal Females: 1/3 rabbits showed hypoactivity, decreased limb tone, ataxia, anorexia

Gross pathology:

The rabbit which died during the study period: Stomach, pale green fluid contents; Stomach, white mucoid material adhering to mucosa; Lungs, severe congestion and consolidation; Lungs, white film adhering. The death of the rabbit was attributed to pneumonia.
Rabbits which were sacrificed following 14 days of observation: No gross lesions- 2/3 males and 2/2 females
Kidneys, mottled coloration- 1/3 males

Other findings:

- Organ weights: None
- Histopathology: None
- Potential target organs: None
- Other observations: None

None

Conclusions:

The LD50 of dodecyl dimethyl amine oxide is >560 mg/kg based (or > 2000 mg/kg bw nominal P7270).

Executive summary:

The LD50 of dodecyl dimethyl amine oxide is > 560 mg AO/kg BW (or >2000 mg/kg bw nominal P7270).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

Acute oral toxicity:

No studies are available on C12 AO. However, reliable studies are available for C12 -14 AO, where the C12 AO made up approximately 60 -80 % of the substance, with C14 AO being the other main constituent. It is valid to read across from C12 -14 AO to C12 AO on this basis.

In a study performed according to OECD TG 401 using C12 -14 AO [Fulfs JC (1978)] 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, petechiae 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 petechiae on lungs and gas in stomach (5800 mg/kg bw). The LD50 was 3800 mg/kg bw, equivalent to 1064 mg AO/kg bw. Reliable supporting studies are available for C12 -14 AO, where the C12 AO made up approximately 60 -80 % of the substance, with C14 AO being the other main constituent. The LD 50 values obtained from these studies were >300 mg AO/kg bw [Gill CRB (1977)] and >600 mg AO/kg bw [Jones JR, Hewitt DS & Warner PA (1986); Hofmann T (1987); Gunn J & Goodwin M (1983)].

Acute dermal toxicity:

No data are available for C12 AO. Studies are available for C10 AO, C12 -14 AO and C12 -18 AO, however. As the range of chainlengths covered by these substances includes C12 AO, it is considered to be acceptable to read-across from these studies to the C12 AO in a weight of evidence approach. In a study performed according to OECD TG 402 under GLP [Haferkorn J (2012b)] C10 AO 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, signs of systemic toxicity or of erythema or oedema during the 14 -day observation period and animals showed the expected bodyweight gains. Necropsy revealed no macroscopic findings. The LD50 was > 2000 mg AO/kg bw. In a second study [Haferkorn J (2010)] performed according to OECD TG 402 under GLP C12-18 AO 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 a third study, performed according to OECD TG 402 [Dean WP (1978)] 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). Based on the results of these studies it is concluded that the LD50 of C12 AO will be > 2000 mg/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 classification or non-classification

Acute oral toxicity: Classification for C12 AO is based on read-across to the study performed using C12 -14 AO [Fulfs JC (1978)] where the LD50 (rat) was 1064 mg AO/kg bw. Based on this result the classification is Acute Toxicity 4, with the Hazard Statement H302: Harmful if swallowed.

Acute dermal toxicity: Based on a weight of evidence approach using studies performed on C10 AO [Haferkorn j (2012b)], C12-14 AO [Dean WP (1978)] and C12-18 AO [Haferkorn J (2010)] it is expected that the LD50 (rat) > 2000 mg AO/kg bw. On the basis of this study 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.