Oligomerisation products of 2,2'-[(1-methylethylidene)bis(4,1-phenyleneoxymethylene)]bisoxirane with acrylic acid and fatty acids, C18-unsatd., dimers and nonanoic acid

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From October 12, 2011 to October 26, 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Principles of method if other than guideline:

The study also followed this guideline: "Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000; including the most recent partial revisions".

GLP compliance:

yes

Test material

Test material information

1

Reference substance name:

Oligomerisation products of 2,2'-[(1-methylethylidene)bis(4,1-phenyleneoxymethylene)]bisoxirane with acrylic acid and fatty acids, C18-unsatd., dimers and nonanoic acid

EC Number:

701-359-2

Cas Number:

216689-76-8

Molecular formula:

Molecular formula not available for this UVCB.

IUPAC Name:

Oligomerisation products of 2,2'-[(1-methylethylidene)bis(4,1-phenyleneoxymethylene)]bisoxirane with acrylic acid and fatty acids, C18-unsatd., dimers and nonanoic acid

Test material form:

liquid

Specific details on test material used for the study:

Specific Gravity / Density: 1.14 g/cm3; pH: (1% in water, indicative range) 5.5 – 5.5 (determined at NOTOX); Stability at higher temperatures: yes, maximum temperature 40°C.

Test animals

Species:

rat

Strain:

Wistar

Remarks:

strain, Crl:WI (Han) (outbred, SPF-Quality).

Sex:

male/female

Details on test animals or test system and environmental conditions:

Source: Charles River Deutschland, Sulzfeld, Germany. Number of animals 5 males and 5 females (females were nulliparous and non-pregnant). Age and body weight: young adult animals (approx. 11 weeks old) were selected. Body weight: variation did not exceed +/- 20% of the sex mean. Identification: earmark. Health inspection: a health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of health. Special attention was paid to the skin to be treated, which was intact and free from any abnormality.
Conditions: Animals were housed in a controlled environment, in which optimal conditions were considered to be approximately 15 air changes per hour, a temperature of 21.0 ± 3.0ºC (actual range: 19.3 – 21.2ºC), a relative humidity of 40-70% (actual range: 46 - 73%) and 12 hours artificial fluorescent light and 12 hours darkness per day. Accommodation: individually housed in labeled Makrolon cages (MIII type, height 18 cm.) containing sterilized sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) 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. During the acclimatization period the animals were group housed in Makrolon cages (MIV type, height 18 cm). Diet: free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany). Water: free access to tap water. Results of analysis for diet (nutrients and contaminants), sawdust, paper and water were assessed and did not reveal any findings that were considered to have affected the study integrity. All certificates and results of analysis are retained in the NOTOX archives.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

polyethylene glycol

Details on dermal exposure:

The formulations (w/w) were prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level. Adjustment was made for specific gravity of test substance and vehicle. In consultation with the sponsor, in order to obtain homogeneity, the test substance and test substance formulations were heated in a water bath with a maximum temperature of 55.8ºC for 21 minutes. The test substance formulations were allowed to cool down to a temperature of maximally 25.3ºC prior to dosing.

Duration of exposure:

24h, after which dressings were removed and the skin cleaned of residual test substance using tap water.

Doses:

2000 mg/kg (10 mL/kg) body weight

No. of animals per sex per dose:

5 males and 5 females

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

Chromodacryorrhoea was noted in two males and one female on Day 1 only. Yellow discolouration of the back, scabs on the treated skin and/or scales on the back and/or treated skin were observed among the animals. No clinical signs were noted for one male and four females.

Body weight:

The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.

Gross pathology:

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

Other findings:

One male showed diaphragmatic hernia of the median lob of the liver. This is occasionally noted among rats of this age and strain and was considered not toxicologically significant.

Any other information on results incl. tables

A dermal LD50 value was derived. The results were evaluated according to: Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2007), and Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labelling and packaging of substances and mixtures.

Applicant's summary and conclusion

Interpretation of results:

other: CLP criteria not met

Conclusions:

Under the study conditions, the acute dermal toxicity of the test substance was > 2000 mg/kg bw.

Executive summary:

A study was conducted to determine the acute dermal toxicity of the test substance according to OECD Guideline 402, EU Method B.3 and EPA OPPTS 870.1200. The substance was administered to five Wistar rats of each sex by a single dermal application at 2000 mg/kg bw for 24 h. Animals were subject to daily observations and weekly determinations of body weight. Microscopic examination was performed at terminal sacrifice (Day 15). No mortality occurred. Chromodacryorrhoea was noted in two males and one female on Day 1 only. Yellow discolouration of the back, scabs on the treated skin and/or scales on the back and/or treated skin were observed. No clinical signs were noted for one male and four females. The mean body weight gain during the observation period was within the range expected for rats used in this type of study. Finally, no toxicologically relevant abnormalities were found at macroscopic post mortem examination. Under the study conditions, the acute dermal toxicity of the test substance was > 2000 mg/kg bw (Stitzinger, 2011).