N,N-Bis(2-hydroxyethyl)-C12-18(even numbered, C18 unsaturated) alkyl-1-amine oxides

Endpoint summary

Description of key information

LD0 > 250 mg/kg

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Start of experiment: 2012-03-28; End of experiment (last necropsy): 2012-05-25

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

no guideline followed

Principles of method if other than guideline:

For the dose-range finding puspose, the rats were treated for seven days at doses of up to 1000 mg/kg bw.
Although the study design does not correspond to any of the current study guideline for acute oral toxicity assessment, the obtained result is considered to be sufficiently evident for a reilable acute oral toxicity assessment.

GLP compliance:

yes (incl. QA statement)

Test type:

other: 7-day repeated dose toxicity study

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Species and strain: Crl:WI rats
Source: Charles River Laboratories, Germany GmbH, Sandhofer Weg 7, D-97633
Hygienic level: SPF at the supplier, standard laboratory conditions during the study
Number of animals: 8 male and 8 female rats
Age of animals: Young adult virgin rats, 10-11 weeks at starting; the
age range within the study was kept to the minimum
practicable.
Body weight: Did not exceed ± 20% of the mean weight for each
sex at onset of treatment: 369-399 g (males) and 249-269 g (females)
Acclimation period: At least 5 days (staggered treatment)

Route of administration:

oral: gavage

Vehicle:

water

Doses:

0, 62.5, 250 and 1000 mg/kg bw

No. of animals per sex per dose:

2

Control animals:

yes

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 250 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no significant toxicity within seven days of repeated dose; the dose level of 250 mg/kg bw can be safely regarded as LD0

Sex:

male/female

Dose descriptor:

LD100

Effect level:

< 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: the animals died after second or third application at daily dose of 1000 mg/kg bw; the LD100 should be regarded as < 2000 mg/kg bw

Study results

At daily dose of 1000 mg/kg bw all animals (two males and two females) died after second or third application. The clinical signs observed prior to death included decreased activity, gasping respiration, salivation, piloerection, lethargy, hunched back and lacrimation. These animals exhibited severe body weight loss prior to death. At necropsy evaluation, the findings in dead animals were dark/red discoloratioin of the enlarged lungs, white foamy material in the trachea, enlarged adrenals, dark/red discoloration/focus on the thymus or glandular/non glandular stomach, mucoid material mixed with diet within the stomach, yellow/brown mucoid material in the digestive content of the duodenum, jejunum, ileum, cecum, colon and/or rectum. Additionally, clear liquid material at the perioral/periorbital area and/or red discoloration of the periorbital/perinasal area and yellow/brown discoloured nerinasal area, were also found.

At daily dose of 250 mg/kg bw all animals (two males and two females) survived the seven days application. One female exhibited sneezing, gasping respiration, piloerection, noisy respiration, salivation, decreased activity and incoordinated movement and one male exhibited increased respiration. In addition, reduced body weight gain and reduced food consumption were found, whereas the effect was more pronounced in the first three days. At necropsy at the end of the observation period, thickened/rough surface non glandular mucosa of the stomach was found in 3/4 rats.

At daily dose of 62.5 mg/kg bw all animals (two males and two females) survived the seven days application. The clinical signs observed were limited to noisy respiration in one female and increase respiration rate in one male. The body weight gain and the food consumption were also slightly affected.

Tab: Body weight development [g]; individual values and mean
Dose group		Males			Females
		Day 0	Day 3	Day 6	Day 0	Day 3	Day 6
Control	Value 1	369	382	393	265	265	273
	Value 2	398	408	433	253	246	248
	Mean	384	395	413	259	256	261
62.5 mg/kg bw/day	Value 1	392	408	411	259	243	244
	Value 2	375	368	375	249	249	255
	Mean	384	388	393	254	246	250
250 mg/kg bw	Value 1	377	337	343	251	235	241
	Value 2	399	389	400	265	222	194
	Mean	388	363	372	258	229	218

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The oral acute toxicity is derived based on the findings in the seven days repeated dose toxicity study. The LD50 is assessed to be in the range of harmful upon ingestion.
With respect to the classification and labelling according to GHS, the Acute Tox.4 should be assigned.
With respect to the classification and labelling according to 67/548/EEC (DSD), Xn; R22 should be assigned.

Executive summary:

For the dose-range finding puspose, the rats were treated for seven days at doses of up to 1000 mg/kg bw.

Although the study design does not correspond to any of the current study guideline for acute oral toxicity assessment, the obtained result is considered to be sufficiently evident for a reilable acute oral toxicity assessment.

All animals treated at daily dose of 1000 mg/kg bw died after second or third application, whereas all animals treated at daily dose of 250 mg/kg bw survied the scheduled applicaiton of seven days.

Based on those findings, the test item can reliably be considered as harmful upon ingestion.

With respect to the classification and labelling according to GHS, the Acute Tox.4 should be assigned.

With respect to the classification and labelling according to 67/548/EEC (DSD), Xn; R22 should be assigned.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating dose

Value:

250 mg/kg bw

Quality of whole database:

One key study and two supporting experiments; consistent results were obtained

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity

For the dose-range finding puspose, the rats were treated with registration substance for seven days at doses of up to 1000 mg/kg bw.

Although the study design does not correspond to any of the current study guideline for acute oral toxicity assessment, the obtained result is considered to be sufficiently evident for a reilable acute oral toxicity assessment.

All animals treated at daily dose of 1000 mg/kg bw died after second or third application, whereas all animals treated at daily dose of 250 mg/kg bw survied the scheduled applicaiton of seven days.

Based on those findings, the registration substance can reliably be considered as harmful upon ingestion.

With respect to the classification and labelling according to GHS, the Acute Tox.4 should be assigned.

 

Justification for selection of acute toxicity – oral endpoint
Scientifically well-performed study

Justification for classification or non-classification

Based on the experimental result, the registration substance can reliably be considered as harmful upon ingestion.

With respect to the classification and labelling according to GHS, the Acute Tox.4 should be assigned.