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

Endpoint summary

Description of key information

The registration substance is of low acute and dermal toxicity.

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:

2015-12-15 to 2016-04-11

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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

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

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.

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.

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

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

One recently performed guideline study.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

27 May 2016 to 05 July 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Not applicable

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

OECD Guidelines for Testing of Chemicals No. 402 (Section 4: Health Effects) “Acute Dermal Toxicity” adopted on 24 February 1987

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: In-house bred animals
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 10 Weeks
- Weight at study initiation: 222.85 g to 236.20 g (males); 210.48 g to 216.07 g (females)
- Fasting period before study: Not applicable
- Housing: housed individually in a standard polypropylene cage (Size: L 430 x B 285 x H 150 mm)
- Diet (e.g. ad libitum): Teklad Certified (2014SC) Global 14 % Protein Rodent Maintenance Diet - Pellet, manufactured by Envigo Laboratories
- Water (e.g. ad libitum): Deep bore-well water passed through activated charcoal filter and exposed to ultraviolet rays in Aquaguard water filter with purifier
- Acclimation period: 5 Days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.0 to 22.6°C
- Humidity (%): 50 to 69%
- Air changes (per hr): 12 to 15
- Photoperiod (hrs dark / hrs light): 12 hours fluorescent light and 12 hours dark cycle

IN-LIFE DATES: From: 27 May 2016 To: 15 June 2016

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorso-lateral area of the trunk
- % coverage: 10% of the total body surface area
- Type of wrap if used: semi-occlusive dressing (crepe bandage)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): using distilled water and dried with absorbent cotton
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg body weight
- Concentration (if solution): Undiluted

Duration of exposure:

24 hours

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observed for clinical signs of toxicity and mortality at 30 to 40 min, 1 hour (±10 minutes), 2 hours (±10 minutes), 3 hours (±10 minutes) and 4 hours (±10 minutes) post application of the test item on Day 1 and once daily thereafter for clinical signs of toxicity and twice daily for mortality during the experimental period.

Individual animal body weight was recorded at receipt and on Day 1 (before test item application) and on days 8 and 15 during the experimental period.

- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

Not applicable

Preliminary study:

Not applicable

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr.

Mortality:

The animals did not reveal any mortality during the observation period

Clinical signs:

other: The animals did not reveal any clinical signs of toxicity during the observation period

Gross pathology:

No treatment related gross pathological findings were observed in any of the animals sacrificed at the end of the experimental period.

SUMMARY OF CLINICAL SIGNS OF TOXICITY AND MORTALITYRECORD

Test	Dose (mg/kg body weight)	No. of Animals	Sex	Clinical Signs of Toxicity	Mortality (No. of Mortality/ No. of Animals Dosed)
Limit Test	2000	5	M	N	0/5
Limit Test	2000	5	F	N	0/5

SUMMARY OF BODY WEIGHT (g) AND PERCENT CHANGE IN BODY WEIGHT WITH RESPECT TO DAY 1

Test	Dose (mg/kg body weight)	Sex		Body Weight (g) on Day 1	Body Weight (g) on Day 8	Body Weight (g) on Day 15		PercentChange in Body Weight with Respect to Day 1on Day 8	PercentChange in Body Weight with Respect to Day 1on Day 15
Limit Test	2000	M	Mean	256.28	278.86	309.23		8.76	20.61
			±SD	9.89	15.07	18.11		2.14	3.53
			n	5	5	5		5	5
Limit Test	2000	F	Mean	222.74	231.8	242.25		4.07	8.76
			±SD	3.58	3.72	4.82		0.48	1.11
			n	5	5	5		5	5

SUMMARY OF GROSS PATHOLOGICAL FINDINGS

Test	Dose (mg/kg body weight)	No. of Animals	Sex	Fate	External Gross Pathology Findings	Internal Gross Pathology Findings
Limit Test	2000	5	M	TS	NAD	NAD
Limit Test	2000	5	F	TS	NAD	NAD

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal toxicity of the registration substance was investigated according to the Guideline OECD 402. Rats were treated at dose of 2000 mg/kg bw. No effects were found. No classification is warranted.

Executive summary:

The acute dermal toxicity of the registration substance was investigated according to the Guideline OECD 402. Five female and five male rats were treated dermally (semi-occlusive) with N,N-Dimethyl-D-Glucamine at dose of 2000 mg/kg bw for 24 hours, 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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

One recently performed guideline study.

Additional information

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.

The acute dermal toxicity of the registration substance was investigated according to the Guideline OECD 402.Five female and five male rats were treated dermally (semi-occlusive) with N,N-Dimethyl-D-Glucamine at dose of 2000 mg/kg bw for 24 hours, 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.

Justification for classification or non-classification

In acute oral toxicity study (OECD 423) no effect was observed at limit dose of 2000 mg/kg bw.

In acute dermal toxicity study (OECD 402) no effect was observed at limit dose of 2000 mg/kg bw.

No classification is justified.