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Toxicological information

Acute Toxicity: oral

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Administrative data

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:
other: Scientifically well-performed and well-documented study; GLP study; Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Test guideline
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. certificate)
Test type:
other: 7-day repeated dose toxicity study
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Chemical name: Ethanol, 2,2'-iminobis-, N-coco alkyl derivs., N-oxides
Other names: N,N-Bis(2-hydroxyethyl)(coconut oil alkyl)amine oxide
CAS number: 61791-47-7
Batch number: DEG4108213
Molecular weight: 303
Appearance: Light brown, honey-coloured; slightly viscous, clear
liquid at room temperature
Purity (active content): 36.4 % (w/w)
Manufacture date: 25 January 2010
Expiry date: 20 November 2012
Storage conditions: Room temperature (15-25oC, below 70 RH%)

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals 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)

Administration / exposure

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

Results and discussion

Effect levelsopen allclose all
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

Any other information on results incl. tables

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

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
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.