Registration Dossier

Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

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

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
Environmental controls for the animal room were set to maintain 18 to 24°C, a relative
humidity of 40 to 70%, at least 10 air changes/hour, and a 12-hour light/12-hour dark cycle.
Any variations to these conditions were maintained in the raw data and had no effect on the
outcome of the study.
Accommodation
Group housing of 3 animals per cage in labeled Makrolon cages (MIV type; height 18 cm.)
containing sterilized sawdust as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier &
Söhne GmbH + CO. KG, Rosenberg, Germany) and paper as cage-enrichment (Enviro-dri,
Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom).
Acclimatization period was at least 5 days before start of treatment under laboratory
conditions.
Diet
Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest,
Germany).
Water
Free access to tap water.
Diet, water, bedding and cage enrichment evaluation for contaminants and/or nutrients was
performed according to facility standard procedures. There were no findings that could
interfere with the study.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Oral gavage, using plastic feeding tubes. The test item was
stirred on a magnetic stirrer during dosing.
Doses:
2000 mg/kg (2.17 mL/kg) body weight.
Dose volume calculated as dose level (g/kg) / specific gravity.
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
The toxicity of the test item was assessed by stepwise treatment of groups of 3 females. The
first group was treated at a dose level of 2000 mg/kg. The absence or presence of mortality of
animals dosed at one step determined the next step, based on the test procedure defined in the
guidelines. The onset, duration and severity of the signs of toxicity were taken into account
for determination of the time interval between the dose groups.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 value of GR-86-6599 in Wistar rats was established to exceed 2000 mg/kg
body weight.
According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed
5000 mg/kg body weight.
Based on these results, GR-86-6599 does not have to be classified and has no obligatory
labelling requirement for acute oral toxicity according to the Globally Harmonized System of
Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all
amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging
of items and mixtures (including all amendments).
Executive summary:

Assessment of acute oral toxicity with GR-86-6599 in the rat (Acute Toxic Class Method).

The study was carried out based on the guidelines described in:

OECD No.423 (2001) "Acute Oral Toxicity, Acute Toxic Class Method"

Commission Regulation (EC) No 440/2008, B1 tris: "Acute Oral Toxicity, Acute Toxic Class

Method"

EPA, OPPTS 870.1100 (2002), "Acute Oral Toxicity"

JMAFF Guidelines (2000), including the most recent revisions.

GR-86-6599 was administered by oral gavage to two consecutive groups of three female

Wistar rats at 2000 mg/kg body weight. Animals were subjected to daily observations and

weekly determination of body weight. Macroscopic examination was performed after

terminal sacrifice (Day 15).

No mortality occurred.

Hunched posture and piloerection were noted for all animals on Days 1 and/or 2.

The mean body weight gain shown by the animals over the study period was considered to be

normal.

No abnormalities were found at macroscopic post mortem examination of the animals.

The oral LD50 value of GR-86-6599 in Wistar rats was established to exceed 2000 mg/kg

body weight.

According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed

5000 mg/kg body weight.