Amines, C12-18-alkyldimethyl, N-oxides

Endpoint summary

Description of key information

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

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

846 mg/kg bw

Quality of whole database:

Two reliable studies performed on the susbtance itself and six reliable studies on a read across substance.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

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 - one performed ont he susbtance itself and one on a read across substance.

Additional information

Acute oral toxicity:

Two reliable studies are available for C12-18 AO and six for C12-14 AO. All the studies have been performed with commercial grades of amine oxide (AO) as supplied (normally an approximately 30 % aqueous solution). In the key study [Rupprich N & Weigand W (1983)] performed according to OECD TG 401 groups of rats (Wistar) were dosed by gavage at 1250, 2000, 2500 or 3150 mg test material/kg bw (females, 5/group) or 3150, 4000 or 5000 mg test material/kg bw (males, 5/group) (equivalent to 375, 600, 750 or 945 mg AO/kg bw for females and 945, 1200 or 1500 mg AO/kg bw for males). One female died in the 2500 mg/kg bw group and 4 died in the 3150 mg/kg bw group, whilst 3 males died in the 4000 mg/kg bw group and 4 in the 5000 mg/kg bw group. Signs of toxicity included ruffled fur in all groups, diarrhoea, squatting and subdued behaviour at doses of 2000 mg/kg bw and higher, narrow palpebral fissures from 2500 m/kg bw. Necropsy revealed no visible macroscopic findings in 1250 or 2000 mg/kg bw females. At higher doses findings included gastrointestinal tract filled with yellow fluid & full bulging stomach (2500 mg/kg bw) protruding gastrointestinal tract vessels, tract filled with reddish or yellow fluid, thorax filled with pink fluid, full bulging stomach, autolysis (advanced) (3150 mg/kg bw females). There were no visible macroscopic abnormalities in the 3150 mg/kg bw males. Findings at higher doses included full bulging stomach, small intestine filled with yellowish-green liquid, autolysis (early stages) and liver lightened. The LD50 was 2820 mg/kg bw, equivalent to 846 mg AO/kg bw for females and 4120 mg/kg bw, equivalent to 1236 mg AO/kg bw for males.

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

Jones JR et al (1986) dosed rats (Sprague-Dawley, 5 animals/sex) by gavage with 2000 mg/kg bw of a 30 % solution of C12 -14 AO in a limit test performed according to OECD TG 401 under GLP. There were no deaths during the study. All the animals showed hunched posture and piloerection one and four hours after treatment. All animals recovered and appeared normal on day 1 and for the rest of the study period. All animals showed normal gains in bodyweight. Abnormalities noted at necropsy were scattered white raised areas covering approximately 25 % of the non-glandular region of the stomach. No other abnormalities were noted. Based on these results the LD50 was > 2000 mg/kg bw, equivalent to > 600 mg AO/kg bw. Hofmann T (1987) also dosed rats (Wistar, 5 animals/sex) by gavage with 2000 mg/kg bw of a 30 % solution of C12 -14 AO in a limit test performed according to OECD TG 401 under GLP. There were no deaths or clinical signs noted during the study period. Bodyweight gains were not impaired and there were no macroscopically visible changes noted at necropsy. Based on these results the LD50 was > 2000 mg/kg bw, equivalent to > 600 mg AO/kg bw. In the three further studies, 5600 mg/kg bw (equivalent to 1680 mg AO/kg bw) [Bullens P (1984)], >2000 mg/kg bw (equivalent to > 600 mg AO/kg bw) [Gunn J & Goodwin M (1983)] and >5000 mg/kg bw (equivalent to >300 mg AO/kg bw) [Gill CRB (1977)].

Acute dermal toxicity:

Two studies are available. The key study [Haferkorn J (2010)] was performed using C12 -18 AO. In this study, performed according to OECD TG 402 under GLP the test substance was applied as a solution in water to the skin of 5 male and 5 female rats (CD/Crl: CD(SD)) at a dose of 2000 mg AO/kg bw and covered with an occlusive dressing for 24 hours. After completion of the exposure period the dressing was removed. There were no deaths or signs of systemic toxicity during the 14 -day observation period and animals showed the expected bodyweight gains. Erythema (grade 2-4) was observed at the application site in all 5 males and 5 females immediately after patch removal until test day 6. No Oedema was observed in any animal at any time period. Erythema was not observed from day 7 onwards (Grade = 0). Necropsy revealed no macroscopic findings. The LD50 was > 2000 mg AO/kg bw. In the second study, performed according to OECD TG 402 [Dean WP (1978a)] C12 -14 AO was applied as a solution in water to the skin of 3 male and 3 female rabbits (New Zealand White) at a dose of 2000 mg. kg bw (equivalent to 560 mg AO/kg bw) and covered with an occlusive dressing for 24 hours. One rabbit died during the observation period. This death was attributed to pneumonia and was not considered to be related to treatment. One female rabbit showed hypoactivity, decreased limb tone ataxia and anorexia. Surviving animals showed expected bodyweight gains. Necropsy revealed pale green fluid and white mucoid material adhering to mucosa in the stomach, severe congestion, consolidation and white film adhering in the lungs of the animal that died of pneumonia. In the surviving animals no gross lesions were noted except mottled colouration in the kidneys of one male. The LD50 >2000 mg/kg bw (equivalent to > 560 mg AO/kg bw).

Acute inhalation toxicity:

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

Justification for selection of acute toxicity – oral endpoint
Study chosen because it was performed on the substance itself and gives the lowest definitive LD50 value

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

Justification for selection of acute toxicity – dermal endpoint
Reliable study performed on the substance itself.

Justification for classification or non-classification

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

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

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