Reaction mass of 1,1'-oxybis(ethylbenzene) and Styrene, oligomers

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2014-2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to OECD and GLP guidelines, and was considered relevant, adequate and reliable.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000; including the most recent partial revisions.

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of (1,1’ oxybis(ethylbenzene) and styrene, oligomers

IUPAC Name:

Reaction mass of (1,1’ oxybis(ethylbenzene) and styrene, oligomers

Constituent 2

Reference substance name:

SMPO Heavy Ends

IUPAC Name:

SMPO Heavy Ends

Test material form:

liquid: viscous

Details on test material:

- Name of test material (as cited in study report): SMPO Heavy Ends; Reaction mass of (1,1’ oxybis(ethylbenzene) and styrene, oligomers
- Substance type: UVCB
- Physical state: Brown liquid
- Analytical purity: 100% (UVCB)
- Purity test date: No data
- Lot/batch No.: BC604 17-10-2014
- Expiration date of the lot/batch: No data
- Stability under test conditions: Not indicated
- Storage condition of test material: At room temperature protected from light
- Other: pH (1% in water, indicative range) = 6.2 - 6.7 (determined by WIL Research Europe)

Test animals

Species:

rat

Strain:

other: Wistar Crl:WI (Han) (outbred, SPF-Quality)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: Young adult animals (approx. 9-10 weeks old) were selected.
- Weight at study initiation: Body weight variation did not exceed +/- 20% of the sex mean.
- Fasting period before study: Animals were deprived of food overnight prior to dosing and until 3-4 hours after administration of the test substance. Water was available ad libitum.
- Housing: 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).
- Diet (e.g. ad libitum): Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: At least 5 days before start of treatment under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24 °C
- Humidity (%): 40 to 70%
- Air changes (per hr): At least 10 air changes/hour
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 10 December 2014 To: 30 December 2014

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED:
Dose level (volume): 2000 mg/kg (1.92 mL/kg) body weight.
Dose volume calculated as dose level (g/kg) / density (g/mL)

Doses:

2000 mg/kg (1.92 mL/kg) body weight.

No. of animals per sex per dose:

6. The toxicity of the test substance 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.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing:
Mortality/Viability: twice daily.
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15. The signs were graded according to fixed scales and the time of onset, degree and duration were recorded:
Maximum grade 4 : grading slight (1) to severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1)
- Necropsy of survivors performed: yes. At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.

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

Based on:

test mat.

Remarks on result:

other: no mortality observed

Mortality:

No mortality occurred.

Clinical signs:

other: Lethargy, ventro-lateral recumbency, flat posture, hunched posture, uncoordinated movements, piloerection, ptosis and/or hypothermia were noted for the animals between Days 1 and 4.

Gross pathology:

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

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The oral LD50 value of SMPO Heavy ends 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 be 5000 mg/ kg body weight.
Based on these results:
- according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011) (including all amendments), SMPO Heavy ends should be classified as: may be harmful if swallowed (Category 5) for acute toxicity by the oral route.
-according to the Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures (including all amendments), SMPO Heavy ends does not have to be classified and has no obligatory labelling requirement for oral toxicity

Executive summary:

Assessment of acute oral toxicity with SMPO Heavy ends in the rat was conducted according to the Acute Toxic Class Method (OECD No. 423). The substance was administered undiluted by oral gavage to two subsequent 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. Lethargy, ventro-lateral recumbency, flat posture, hunched posture, uncoordinated movements, piloerection, ptosis and/or hypothermia were noted for the animals between Days 1 and 4. The 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 SMPO Heavy ends in Wistar rats was established to exceed 2000 mg/kg body weight.

According to the Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures (including all amendments), SMPO Heavy ends does not have to be classified and has no obligatory labelling requirement for oral toxicity.