Registration Dossier

Administrative data

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:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
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 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:
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.

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:
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. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals 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:
The animals did not reveal any clinical signs of toxicity during the observation period
Body weight:
No treatment related changes were noted in the body weight and percent change in body weight with respect to Day 1 in both male and females
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.