Registration Dossier

Administrative data

Description of key information

Acute oral toxicity: Five reliable studies are available 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 [Fulfs JC (1978)], the reported LD50 (rat) was 3800 mg/kg bw, equivalent to 1064 mg AO/kg bw.

Acute dermal toxicity: The key study was performed using category member C12-18 AO. In this study the reported LD50 (rat) was > 2000 mg AO/kg bw [Haferkorn J (2010)].

Acute inhalation toxicity: No studies are available.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

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:
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:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
2011-11-28 to 2012-02-03
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals 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: ca. 8 weeks
- Weight at study initiation: 160-194 g
- Fasting period before study: yes, ca. 16 hours before start
- Housing: MAKROLON cages (type III plus) with granulated textured wood as bedding.
- Diet (e.g. ad libitum): ad libitum prior to fasting period and in recovery period
- Water (e.g. ad libitum): ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 55 ± 15%
- Air changes (per hr): Not specified
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

IN-LIFE DATES: From: 2011-11-28 To: 2011-12-29
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 5.09 mL/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: based on toxicity information from study sponsor.
Doses:
300 and 2000 mg AO/kg bw
No. of animals per sex per dose:
6 animals at 300 mg AO/kg bw
3 animals at 2000 mg AO/kg bw
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 surviving animals were observed for a period of 14 days.
During the follow-up period of two weeks, changes of skin and fur, eyes and mucous membranes, respiratory and the circulatory, autonomic and central nervous system and somatomotor activity, as well as behaviour pattern were observed at least once a day until all symptoms subsided, thereafter each working day. Attention was also paid to possible tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Observations on mortality were made at least once daily to minimize loss of animals during the study. Individual body weights were recorded before administration of the test item and thereafter in weekly intervals up to the end of the study and at death. Changes in weight were calculated and recorded.

- Necropsy of survivors performed: yes
Statistics:
No applicable
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
act. ingr.
Mortality:
300 mg AO/kg bw: No animal died prematurely.
2000 mg AO/kg bw: Two of 3 animals died prematurely within 6 hours after administration.
Clinical signs:
Under the present test conditions, a single oral administration of 300 mg N,N-dimethyldecylamine-N-oxide/kg b.w. to female rats revealed slight salivation in 4 of 6 animals.
A single oral administration of 2000 mg N,N-dimethyldecylamine-N-oxide/kg b.w. to female rats revealed slight salivation in 3 of 3 animals.
Body weight:
All surviving animals gained the expected body weight.
Gross pathology:
No pathological changes were observed at necropsy.

Table 1: Summary of results

Symptoms/criteria

300 mg AO/kg bw

2000 mg AO/kg bw

Females (n = 3)

First step

Females (n = 3)

Second step

Females (n = 3)

First step

Clinical signs:

salivation

+

15’

(3)

+

5’-15’

(1)

+

15’

(3)

Mortality:

Within 6h

Within 24h

Within 7d

Within 14d

 

 

 

0

0

2

0

0

2

0

0

2

0

0

2

Mean bodyweight (g)

Start

After 7d

After 14 d

 

 

 

169.0

171.0

185.0

195.0 (+15.5)

198.7 (+16.3)

241.0 (+24.1)

212.7 (+25.9)

220.0 (+28.8)

273.0 (+40.7)

Inhibition of bodyweight gain

none

none

none

Necropsy findings

none

none

none

In brackets:      clinical signs: no of animals affected

                        Bodyweight: bodyweight gain in %, compared to start value

+ = slight

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The acute oral (gavage) LD50 is in the range 300 - 2000 mg AO/kg bw.
Executive summary:

Test Guideline

OECD Guideline 423 and EC Method B1 tris (acute toxic class)

Method and material

In a first step 3 female Sprague-Dawley rats were dosed by oral gavage with 300 mg/kg of the test material as supplied (corrected for active content). As no animals died a further three female rats were dosed at the same dose level. No animals died. Three female rats were then dosed by oral gavage at 2000 mg/kg. Animals were observed for 14 days after dosing for mortalities, bodyweight gain and clinical signs of toxicity. All surviving animals under went necropsy at study termination.

Results

300 mg AO/kg bw: No animal died prematurely.

2000 mg AO/kg bw: Two of 3 animals died prematurely within 6 hours after administration.

Salivation was noted in animals in both dose groups after dose administration. There was no effect on bodyweight gain. There were no macroscopic treatment related effects noted at necropsy.

The acute oral (gavage) LD50 is in the range 300 - 2000 mg AO/kg bw.

Conclusion

In accordance with CLP Regulation (EC) No 1272/2008 the substance is classified as Acute category 4 for oral toxicity.

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:
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 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:
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 Table 1 (attached).
Body weight:
All animals showed normal gains in bodyweight during the main study. Individual bodyweights, together with weekly bodyweight gains are given in Table 2 (attached).
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, a 30% solution of C12-14 AO, 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.
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:
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 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 animals 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:
No clinical symptoms were observed after administration of 2000 mg/kg body weight
Body weight:
Development of body weight was not impaired
Gross pathology:
The animals killed at the end of the observation period showed no macroscopically visible changes
Conclusions:
Acute oral toxicity testing of the test item, a 30% aqueous solution of C12-14 AO, 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.
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:
no guideline followed
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 the 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, a 6% aqueous solution of C12-14 AO, 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.
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:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline followed
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, a 30% aqeous solution of C12-14 AO, 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.
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
31-01-1978 to 28-02-1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Principles of method if other than guideline:
The acute oral toxicity of the test substance was assessed by single oral doses administered by gavage to female rats. Rats were fasted for 16 h before application of the test substance and for 2 h post appplication. Rats were dosed at 3000 and 5000 mg/kg bw with 10 rats per dose. The rats were observed for 14 days, during which they were weighed weekly. All rats underwent macroscopic assessment .
GLP compliance:
no
Remarks:
Study pre-dates GLP
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: SPF-Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 160 to 178 g (mean weight 170 g).
- Fasting period before study: 16 h
- Housing: In plastic cages with wood shavings.
- Diet: Ad libitum Altomin 1324 (Altomin GMBH).
- Water: Ad libitum
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
No data
Doses:
3000 and 5000 mg/kg body weight
No. of animals per sex per dose:
10 females/dose
Control animals:
not specified
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:
No data
Preliminary study:
Not applicable
Sex:
female
Dose descriptor:
LD50
Effect level:
3 000 - 5 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
900 - 1 500 mg/kg bw
Based on:
act. ingr.
Mortality:
At a dose of 5000 mg/kg bw of the test material all 10 animals died within 24 h. At 3000 mg/kg bw of test material one out of 10 rats died.
Clinical signs:
Prior to death animals exhibited decreased respiratory rate, narrowed palpebral fissures and were found in a prone position.
Body weight:
Body weight development of surviving animals was normal.
Gross pathology:
No macroscopic abnormalities were found in surviving animals. In the animals that died, one was found with the intestinal tract full of the preparation. The other necropsies showed no notable observations.
Other findings:
No data

Results:

Dose

(mg/kg)

Concentration

(%)

Number of dead animals/

Number of total animals

3000

25

1/10

5000

25

10/10

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The acute oral toxicity of the test substance was assessed in female rats from a single oral dose. All rats dosed at 5000 mg/kg bw died within 24 h. One rat exposed to 3000 mg/kg bw test substance died. The acute oral LD50 for female rats was between 3000 and 5000 mg/kg/day bw, equivalent to 900 - 1500 mg AO/kg bw.
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
27-09-1983 to 22-11-1983
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Qualifier:
according to
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 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:
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 observed in males and females.
This symptom was observed after 30 - 60 minutes.
Female survivors were free of symtpoms on the first day.
The male survivors on the second day post application were squatting with very noisy breathing and ruffled fur.
Body weight:
There was no reduction of body weight gain.
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
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, equivalent to 1236 mg AO/kg bw. The acute oral LD50 of the test substance in female rats was 2820 mg/kg, equivalent to 846 mg AO/kg bw..
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
not specified
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
20% dilution
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 per sex/dose
Control animals:
no
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 500 mg/kg bw
Based on:
act. ingr.
Mortality:
No mortalities
Clinical signs:
None indicated
Body weight:
No indication of effect on bodyweight.
Interpretation of results:
Toxicity Category IV
Conclusions:
The acute oral median lethal dose (LD50) of the test material to the rat was found to be > 2000 mg/kg bw. This result equates to an LD50 of > 500 mg/kg bw based on active ingredient.
Executive summary:

The acute oral toxicity of C14 AO was assessed in male and female rats in accordance to OECD Guideline No. 401. Five male and five female rats were dosed by oral gavage with 2000 mg/kg bw test material (ca. 25% active). After a 14 day observation period there were no mortalities and no treatment related effects observed on bodyweight or at gross necropsy. The LD50 was > 500 mg AO/kg bw.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1997-10-29 to 1997-12-12
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Sprague-Dawley, Indianapolis, Indiana
- Age at study initiation: 6 to 10 weeks
- Weight at study initiation: 206 - 260 g
- Fasting period before study: Yes, overnight
- Housing: Individually in stainless steel cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
Temperature, humidity and light controlled room (DHEW publication No. 86-23 (NIH))

IN-LIFE DATES: From: 1997-10-29 To: 1997-11-11
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Dosage volume: 5 g/kg
Metal dosing cannula
Doses:
5 g/kg bw
No. of animals per sex per dose:
5 male/5 female
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Frequently on day of dosing (1, 2.5 and 4 hours) and once daily thereafter
- Necropsy of survivors performed: yes
Statistics:
Calculations of the LC50 and 95% confidence limits: Method of moving averages, Weil CC (1952) table for convenient calculations of median effective dose (LD50 and ED50) and instruction in their use. Biometrics, 8.
Preliminary study:
Not performed
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 1 495 mg/kg bw
Based on:
act. ingr.
Mortality:
No mortalities
Clinical signs:
No clinical observations reported
Body weight:
No treatment related effect on bodyweight reported
Gross pathology:
No treatment related effects noted at gross necropsy
Interpretation of results:
Toxicity Category IV
Conclusions:
The acute oral administration of the test material resulted in an LD50 >5000 mg/kg bw, equivalent to > 1500 mg AO/kg bw.
Executive summary:

The acute oral toxicity of C14 AO was assessed in male and female rats in accordance to OECD Guideline No. 401. Five male and five female rats were dosed by oral gavage with 5000 mg/kg bw test material (ca. 30% active). After a 14 day observation period there were no mortalities and no treatment related effects observed on bodyweight or at gross necropsy. The LD50 was > 1495 mg AO/kg bw.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1984-9-13 to 1984-10-18
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:
other: Consumer Product Safety Commission Protocol
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: CD
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River
- Age at study initiation: No data
- Weight at study initiation: 200-300 g
- Fasting period before study: 18 hours
- Housing: raised wire mesh cages
- Diet: Lab Blox ad libitum
- Water: ad libitum
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): No data
- Air changes (per hr): Air conditioned quarters
- Photoperiod (hrs dark / hrs light): No data
Route of administration:
other: Rigid stomach tube
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Following administration of each dose level the animals were observed for fourteen days for signs of toxicity.
Doses:
0.4 mL per 100g bodyweight equating to 4.0 g/kg boidyweight
0.5 mL per 100 g bodeweight equating to 5.0 g/kg bodyweight
0.7 mL per 100 g bodyweight equating to 7.0 g/kg bodyweight
No. of animals per sex per dose:
5 males and 5 females per dose level
Control animals:
no
Details on study design:
The animals were examined daily and mortality recorded. An autopsy was performed if autolysis had not occurred.
Statistics:
The method of Litchfield and Wilcoxon was used to calculate the oral LD50 (see Table 1, attached)
Preliminary study:
No data
Sex:
male/female
Dose descriptor:
LD50
Effect level:
5 600 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:
1 680 mg/kg bw
Based on:
act. ingr.
Mortality:
See Table 1 (attached)
Clinical signs:
See Table 1 (attached)
Body weight:
No data following measurements at start of study
Gross pathology:
Autopsy were performed on rats that did not show any signs of autolysis. At autopsy, no macroscopic changes were noted in any of the internal organs.
Other findings:
No data
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The LD50 was calculated to be 5.6 g/kg bodyweight based on test material. This result equates to an LD50 of 1680 mg/kg bodweight based on active ingredient.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
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

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
21/12/2009 - 19/02/2010
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
1. HYPOTHESIS FOR THE CATEGORY APPROACH (ENDPOINT LEVEL)
Please refer to the Amine Oxide Category justification attached in Section 13

2. CATEGORY APPROACH JUSTIFICATION (ENDPOINT LEVEL
Please refer to the Amine Oxide Category justification attached in Section 13
Reason / purpose:
read-across: supporting information
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:
GHS criteria not met
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:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
24 May - 01 August 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
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, 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:
No clinicals signs of toxicity
Body weight:
All animals gained the expected body weight throughout the whole experimental period
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:
GHS criteria not met
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.

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1978-03-10
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
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 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:
Males: 1-14 days: 3/3 animals appeared to be normal
Females: 1/3 rabbits showed hypoactivity, decreased limb tone, ataxia, anorexia
Body weight:
Body weight gain was seen in surviving animals
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 AO/kg (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
Quality of whole database:
Two reliable studies are available.

Additional information

Acute oral toxicity:

Five reliable studies are available for C12-14 AO. All the studies have been performed with commercial grades of the substance 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, 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.

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 two further studies, LD50 (rat) >2000 mg/kg bw (equivalent to > 600 mg AO/kg bw) [Gunn J & Goodwin M (1983)] and LD50 (rat) >5000 mg/kg bw (equivalent to >300 mg AO/kg bw) [Gill CRB (1977)] were reported.

In addition, supporting studies are available for the following category members:

C10 AO: LD50 (rat) >300 - <2000 mg AO/kg bw, LD50 cut-off value 1000 mg AO/kg bw. (OECD TG 403) [Haferkorn J (2012)].

C14 AO: LD50 (rat) > 1495 mg AO/kg bw (OECD TG 401) [Kukulinski M (1997)]; LD50 (rat) > 500 mg AO/kg bw (OECD TG 401) [Hofmann T (1988)].

C14-16 AO: LD50 (rat) = 1680 mg AO/kg bw/day (CPSC protocol) [Bullens P (1984)].

C12-18 AO: LD50 (rat) >900 – 1500 mg AO/kg bw (non-guideline study) [Mayer & Weigand (1978)]; LD50 (rat) 846 – 1236 mg AO/kg bw/day (OECD TG 401) [Rupprich & Weigand (1983)].

Acute dermal toxicity:

The key study [Haferkorn J (2010)] was performed using the category member 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 a supporting study performed according to OECD TG 402 using C12-14 AO [Dean WP (1978)] 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).

In a supporting study [Haferkorn J (2012)] performed according to OECD TG 402 under GLP using the category member C10 AO, 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, 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.

 

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: 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. Considering 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 category member 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)] and an OECD TG 402 study performed using category member C10 AO which resulted in a LD50 >2000 mg AO/kg bw [Haferkorn J (2012)]. On the basis of these three 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.