D-Glucitol, 1-deoxy-1-(dimethylamino)-

Acute Toxicity: oral

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 guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 3

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

Test material information

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:

other: The test item showed no acute oral toxicity characteristics after a single dose administration.

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.