Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2015-12-15 to 2016-04-11
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report date:
2016

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
(Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit, München, Germany)
Test type:
acute toxic class method

Test material

Constituent 1
Reference substance name:
k.A.
IUPAC Name:
k.A.
Test material form:
solid: flakes
Details on test material:
- Name of test material (as cited in study report): LICOCARE RBW 106 FL TP


Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
Housing and Feeding Conditions
- Full barrier in an air-conditioned room
- Temperature: 22 +/- 3 °C
- Relative humidity: 55 +/- 10%
- Artificial light, sequence being 12 hours light, 12 hours dark
- Air change: 10 x / hour
- Free access to Altromin 1324 maintenance diet for rats and mice (lot no. 0446)
- Free access to tap water, sulphur acidified to a pH value of approximately 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals)
- The animals were kept in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding (lot no. 02102150820)
- Certificates of food, water and bedding are filed for two years at BSL Munich and afterwards archived at Eurofins Munich
- Adequate acclimatisation period (at least five days) under laboratory conditions

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
The animals were marked for individual identification by tail painting.
Prior to the administration a detailed clinical observation was made of all animals. Only healthy animals were used.
Prior to the administration food was withheld from the test animals for 16 to 19 hours (access to water was permitted). Following the period of fasting the animals were weighed and the test item was administered. Food was provided again approximately 4 hours post dosing.
The test item was administered at a single dose by gavage using a feeding tube.
The test item was administered at a dose volume of 10 mL/kg body weight.

Doses:
The starting dose was selected to be 2000 mg active component / kg body weight. No compound-related mortality was recorded for any animal of
step 1 or 2. Based on these results and according to the acute toxic class method regime no further testing was required.
No. of animals per sex per dose:
3 per step (2 steps performed)
Control animals:
no
Details on study design:
All animals were observed for 14 days after dosing for general clinical signs, morbidity and mortality.
Weight Assessment
The animals were weighed on day 1 (prior to the administration) and on days 8 and 15.
Clinical Examination
A careful clinical examination was made several times on the day of dosing (at least once during the first 30 minutes and with special attention
given during the first 4 hours post-dose). Thereafter, the animals were observed for clinical signs once daily until the end of the observation
period.
Cageside observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central
nervous systems and somatomotor activity and behaviour pattern were examined. Particular attention was directed to observations of tremor,
convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Pathology
At the end of the observation period the animals were sacrificed with an overdosage of pentobarbital injected intraperitoneally
(Narcoren®, Merial; lot no.: 250055; expiry date: 31/05/2018) at a dosage of 250-400 mg/kg bw.
All animals were subjected to gross necropsy and examined macroscopically for gross pathological changes. In absence of gross pathological
changes no tissues were preserved for a possible histopathological evaluation.
Statistics:
According to OECD guidelines, the biological relevance of the results is the criterion for the interpretation of results, a statistical evaluation of the
results is not regarded as necessary.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
discriminating dose
Effect level:
2 000 mg/kg bw
Based on:
act. ingr.
Mortality:
none
Clinical signs:
The test item showed no acute oral toxicity characteristics after a single dose administration.
Body weight:
None of the animals showed weight loss during the observation period.
Gross pathology:
With the exception of acute injection of blood vessels in the abdominal region, which is due to the euthanasia injection, no specific gross pathological changes were recorded for any animal.

Any other information on results incl. tables

Clinical Signs - Individual Data

Step Sex Starting Dose (mg/kg bw) Animal No. Observations
1 Female 2000 1 no specific findings during
the whole observation period
2 no specific findings during
the whole observation period
3 no specific findings during
the whole observation period
2 Female 2000 4 no specific findings during
the whole observation period
5 no specific findings during
the whole observation period
6 no specific findings during
the whole observation period

bw = body weight

Absolute Body Weights in g and Body Weight Gain in %

Step Animal No. / Sex Starting Dose (mg/kg bw) Body Weight (g) Body Weight in Comparison
Day 1 Day 8 Day 15 to Day 1 (%)
1 1 / Female 2000 170 193 203 19
2 / Female 164 190 200 22
3 / Female 157 178 183 17
2 1 / Female 2000 167 182 190 14
2 / Female 170 194 197 16
3 / Female 165 190 199 21

bw = body weight

Findings of the Necropsy - Individual Data

Step Animal No. / Sex Starting Dose (mg/kg bw) Organ Macroscopic Findings
1 1 / Female 2000  -  nsf
2 / Female  -  nsf
3 / Female  -  nsf
2 4 / Female 2000  -  nsf
5 / Female  -  nsf
6 / Female  -  nsf

bw = body weight;nsf = no specific findings

LD50Cut-Off

Starting Dose (mg/kg bw) Number of Animals  Number of Intercurrent Deaths LD50Cut-Off
2000 6 0 unclassified

bw = body weight

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral toxicity of the registration substance was investigated according to the Guideline OECD 423. Rats were treated at dose of 2000 mg/kg bw per gavage. No effects were found.
No classification is warranted.
Executive summary:

The acute oral toxicity of the registration substance was investigated according to the Guideline OECD 423. Six female rats were treated orally (per gavage) with N,N-Dimethyl-D-Glucamine at dose of 2000 mg/kg bw, observed for clinical effect, including body weight development and food consumption, for up to 14 days and subjected to necropsy. No effect was found throughout observation period and no effect was found upon gross pathological examination. No classification is warranted.