Amines, C12-16-alkyldimethyl, N-oxides

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

27-09-1983 to 22-11-1983

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Amines, C12-18 (even numbered) -alkyldimethyl, N-oxides

IUPAC Name:

Amines, C12-18 (even numbered) -alkyldimethyl, N-oxides

Constituent 2

Reference substance name:

931-341-1

EC Number:

931-341-1

IUPAC Name:

931-341-1

Details on test material:

- Name of test material: Hoe S 3406 (Alkyl-dimethyl-aminoxid)
- Physical state: Clear liquid
- Molecular weight: ca. 260.
- Lot/batch No.: E 06201846
- Storage condition of test material: In the dark at ca. 22 ºC.
- Other: Density ca 0.97 g/cm2 (20 ºC); pH value in water: 6 - 8 (1 % in distilled water); soluble in water.
Composition: 30 % alkylmethylaminoxid, 70 % water and impurities.
Impurities: Max. 0.3 % free fatty alcohol; max. 0.5 % free amine; max. 0.1 % H2O2.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hoescht AG.
- Age at study initiation:
- Weight at study initiation: Males, mean = 202 g (191 - 219 g ); females, mean = 194 g (185 - 205 g)
- Fasting period before study: 16 h before and 2 h after application.
- Housing: Air-conditioned room in makrolon cages (type 4) on soft wood shavings in groups of 5 animals.
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2 ºC
- Humidity (%): 55 ± 10 %
- Photoperiod (hrs dark / hrs light): 12 h light/12 dark

Administration / exposure

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).

Results and discussion

Preliminary study:

No data

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

4 120 mg/kg bw

Based on:

test mat.

95% CL:

3 400 - 5 010

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

2 820 mg/kg bw

Based on:

test mat.

95% CL:

2 360 - 3 540

Effect levels 3

Sex:

male

Dose descriptor:

LD50

Effect level:

1 236 mg/kg bw

Based on:

act. ingr.

Effect levels 4

Sex:

female

Dose descriptor:

LD50

Effect level:

846 mg/kg bw

Based on:

act. ingr.

Mortality:

There were deaths in the female rats at 2500 mg/kg (1/5) and at 2500 mg/L (4/5).
Deaths in male rats occurred at 4000 mg/kg (3/5) and 5000 mg/kg (4/5).
Animals died at 1 - 2 days post exposure.

Clinical signs:

other: After 10 minutes after treatment male animals were observed squatting or prone on their stomach or side and a narrowing of the lids. After 30 - 60 miniutes these symptoms were also observed in the females. 30 -60 minutes post application diarrhoea was ob

Gross pathology:

The necropsy of the male animals that died during the study showed the stomach and small intestine filled with yellowish-green liquid and partial whitening of the liver was observed. The necropsy of the dead females showed a reddish liquid-filling the gastrointestinal tract. In two animals the thorax was filled with pink liquid. Some animals showed autolytic changes. Surviving animals were free from visible macroscopic changes.

Other findings:

No data

Any other information on results incl. tables

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

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral toxicity of the test substance was assessed in male and female rats according to OECD guideline 401 and EU method B.1. The acute oral LD50 of the test substance in males rats was 4120 mg/kg bw with 95 % confidence limits of 3400 - 5010 mg/kg bw. The acute oral LD50 of the test substance in female rats was 2820 mg/kg with 95 % confidence limits of 2360 - 3540 mg/kg bw.