Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
10 May 2017 - 01 Jun 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

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

Materials and methods

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

Test material

Reference
Name:
Unnamed
Test material form:
liquid
Details on test material:
Appearance: Clear colourless liquid
Purity/Composition: UVCB
Test item storage: At room temperature protected from light
Stable under storage conditions until: 31 March 2018 (expiry date)

Test animals

Species:
rat
Strain:
other: Crl: WI(Han)
Sex:
female
Details on test animals and environmental conditions:
Source: Charles River Deutschland, Sulzfeld, Germany
Number of Animals: 6 Females (nulliparous and non-pregnant). Each dose group consisted of 3 animals.
Age at the Initiation of Dosing: Young adult animals (approximately 11 weeks old) were selected.
Weight at the Initiation of Dosing: 174 to 200 g.

On arrival and following assignment to the study, animals were group housed (up to 5 animals of the same sex and same dosing group together) in polycarbonate cages (Makrolon MIV type; height 18 cm.) containing sterilized sawdust as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) equipped with water bottles.

The actual daily mean temperature during the study period was 21 to 22°C with an actual daily mean relative humidity of 43 to 64%. A 12 hour light/12 hour dark cycle was maintained. Ten or greater air changes per hour with 100% fresh air (no air recirculation) were maintained in the animal rooms.

Pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany) was provided ad libitum throughout the study, except during designated procedures.

Animals were deprived of food overnight (for a maximum of 20 hours) prior to dosing and until 3-4 hours after administration of the test item.

Municipal tap-water was freely available to each animal via water bottles.

Administration / exposure

Route of administration:
oral: gavage
Details on oral exposure:
A single dose of test item was administered to the appropriate animals by oral gavage on Day 1, using a syringe with a plastic gavage cannula attached.
The dose volume for each animal was based on the body weight measurement prior to dosing.
Doses:
The dose levels were based on the OECD test guidelines and were selected from the series 5 (lowest dose level), 50, 300 and 2000 (highest dose level) mg/kg body weight
No. of animals per sex per dose:
6 Females (nulliparous and non-pregnant). Each dose group consisted of 3 animals
Details on study design:
The toxicity of the test item was assessed by stepwise treatment of groups of 3 females. 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. The first group was treated at a dose level of 2000 mg/kg. Based on the results, one additional group was dosed at 2000 mg/kg.
Statistics:
No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
One animal was found dead on Day 6, no further mortality occurred.
Clinical signs:
Hunched posture and piloerection were noted for all animals between Days 1 and 11.
Body weight:
The body weight gain shown by the surviving animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.
Gross pathology:
Abnormalities of the stomach (thickened limiting ridge, isolated perforations, dark red discoloration, dark red discoloration of the glandular mucosa, gray-white discoloration of the forestomach and irregular surface of the forestomach), duodenum (thickened and dark red discoloration), liver (grown together with stomach) and abdominal cavity (watery-cloudy contents) were noted for the animal that was found dead on Day 6.
No abnormalities were found at macroscopic post mortem examination of the surviving animals.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In an OECD 423 study, conducted under GLP, the LD50 (female) of MEA Polyborate 1:1 is >2000 mg/kg bw.