Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
08-29 November 2017 (In-life)
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report Date:
2018

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
17th December 2001
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
Species and strain: Rat, Hsd: Sprague Dawley SD
Sex: Females (nulliparous and non-pregnant)
Age: 6-7 weeks old
Supplier: Envigo RMS s.r.l., San Pietro al Natisone (UD), Italy
Breeder: Envigo RMS B.V., Kreuzelweg 53, 5961 NM Horst, Netherlands
Date of arrival: 02 November 2017
Weight range at arrival: 157-164 g
Acclimatisation period: At least 5 days
Veterinary health check: During acclimatisation period
Animals per cage: 3 during the study; up to 5 during acclimatisation
Housing: Polisulfone solid bottomed cages measuring 59.5×38×20 cm, with nesting material provided into suitable bedding bags
Water: Drinking water supplied to each cage via a water bottle; Water supply ad libitum
Diet: 4 RF 18 diet supplied ad libitum throughout the study
Room lighting: Artificial (fluorescent tubes), daily light/dark cycle of 12/12 hours
Air changes: Approximately 15 to 20 air changes per hour
Temperature: Range 22 °C±2 °C
Relative humidity: Range 55%±15%

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE: water (softened by reverse osmosis).
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10mL/kg bw
- Justification for choice of vehicle: based on solubility
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
Two groups of 3 females (4-hour fasted)
Control animals:
no
Details on study design:
A first group of 3 female animals of approximately 8 week of age, was dosed at a level of 2000 mg/kg bw (Step 1). Mortality did not occur. A second group, similarly composed, was then dosed at the same dose level (Step 2). No mortality occurred. No further doses were investigated since the objective of the study had been achieved.
Statistics:
Not required

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred in either group of three female rats.
Clinical signs:
In the first group of three rats, some clinical signs were observed in all animals on the day of dosing. Hunched posture and ataxia were recorded from 30 minutes after dosing up to 4 hours after dosing, piloerection from two hours up to 4 hours and decreased activity at two hours after dosing. In addition, one animal showed rales at 30 minutes after dosing. This sign recovered at two hours after dosing.

In the second group of three rats, Decreased activity was recorded in all animals from 30 minutes up to 4 hours after dosing, ataxia from 30 minutes up to two hours after dosing, hunched posture and piloerection at 4 hours after dosing. These signs had resolved by Day 2 of the study.
Body weight:
Changes in bodyweight observed during the study were within the expected range for this strain and age of animals, based on historical data.
Gross pathology:
No abnormalities were observed at necropsy.

Any other information on results incl. tables

Summary of findings

Group

Rats

Mortality

1

3 female

0/3

2

3 female

0/3

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
No mortality occurred in the six animals following dosing at 2000 mg/kg bw. Decreased activity, ataxia, hunched posture and piloerection were observed in all animals on the day of dosing but had resolved by Day 2 of the study. The acute toxicity estimate (ATE) is therefore >2000 mg/kg bw. No classification is required for acute toxicity according to CLP criteria.
Executive summary:

The acute toxicity of DMP Tech. (reaction mass of 2-ethyl-2 -(methoxymethyl)-propane-1,3-diol and 2 -ethylpropane-1,3 -diol) was investigated following a single oral administration to the Sprague Dawley rat followed by a 14-day observation period. A first group of three female rats was initially dosed at 2000 mg/kg bw (Step 1). No mortality occurred. Some clinical signs were observed in all animals on the day of dosing: hunched posture and ataxia were recorded from 30 minutes after dosing up to 4 hours after dosing, piloerection from two hours up to 4 hours and decreased activity at two hours after dosing. In addition, one animal showed rales at 30 minutes after dosing. A second group of three female rats was dosed at the same dose level (Step 2). No mortality occurred. Decreased activity was recorded in all animals from 30 minutes up to 4 hours after dosing, ataxia from 30 minutes up to two hours after dosing, hunched posture and piloerection at 4 hours after dosing. Bodyweight changes recorded during the study were within the expected range for this strain and age of animals. Gross necropsy did not reveal any effects of treatment. The acute oral LD50 of DMP Tech. was therefore found to the >2000 mg/kg bw under the conditions of this study.