Fatty acids, linseed-oil, reaction products with bisphenol A-epichlorohydrin polymer and glycidyl neodecanoate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From March 15, 2016 to March 30, 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

Lot Number: #210162718
Reaction products of linseed-oil fatty acids, 4,4'-methylendiphenyldiglycidylether with neodecanoic fatty acid, oxiranylmethylester
Purity 100% as per definition of UVCB
Appearance: brown liquid

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Source: Velaz Prague, Czech Republic
Age at first dose: 8-12 weeks
Acclimation: 5 days prior to the start of treatment
Room temperature: 22 ± 2° C, relative humidity: 55 ± 10%
The light regimen was set to a 12-hour light /12-hour dark cycle
Diet: laboratory food Altromin (Altromin Spezialfutter GmbH, Germany), water: tap water

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

The required amount of the test substance (according to the body weight and dose) was mixed with vehicle (olive oil) shortly before administration. The test substance was administered in a single dose by gavage using a metal stomach tube. Animals were fasted prior to dosing (food but not water were withheld over-night). Following the period of fasting, the animals were weighted and the test substance administered. After the test substance had been administered, food was withheld for further 3-4 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6

Control animals:

no

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

All 6/6 females survived the limit dose of 2000 mg/kg

Clinical signs:

other: Animals lived through observation period without signs of intoxication. Neither change of health nor negative reactions were registered

Gross pathology:

No changes were observed

Interpretation of results:

other: CLP criteria not met

Remarks:

does not require classification

Conclusions:

Under the study conditions, the LD50 of the test substance was greater than 2000 mg/kg, after single oral administration to rats.

Executive summary:

A study was conducted to determine the acute oral toxicity of the test substance according to OECD Guideline 423 (acute toxic class method), in compliance with GLP. Six females were administered the test substance at a concentration of 2000 mg/kg bw by gavage. Animals were observed individually immediately after the administration of the test substance and then 0.5, 1, 2, and 4 h later. Then each animal was inspected daily for the next 14 days. Individual weights of animals were determined shortly before the test substance was administered and weekly thereafter. Weight differences after first and second weeks after administration were calculated and recorded. All test animals were subjected to gross necropsy. All gross pathological changes were recorded for each animal. All 6/6 females survived the limit dose of 2000 mg/kg. Animals lived through observation period without signs of intoxication. Neither change of health nor negative reactions were registered. The body weights of all animals were increasing during the study. No body weight losses were observed between first and second week after administration. No changes were observed at necropsy. Under the study conditions, the LD50 of the test substance was greater than 2000 mg/kg bw, after single oral administration to rats (Hozova, 2016).

Cross-reference 2

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From March 24, 2016 to April 15, 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Specific details on test material used for the study:

Batch no.: #210162718
Composition: reaction products of linseed-oil fatty acids, 4,4'Methylendiphenyldiglycidylether with neodecanoic fatty acid, oxiranylmethylester
Purity: 100 % as per definition of UVCB
Appearance: brown liquid

Species:

mouse

Strain:

CBA/Ca

Sex:

female

Details on test animals and environmental conditions:

Source: AnLab Prague, Czech Republic
Age: at least 8 - 10 weeks old (non-pregnant and nulliparous)
Acclimation: 7 days
Room temperature: 22 ± 2°C, relative humidity: 55 ± 10 %
The light regimen was set to a 12-hour light / 12-hour dark cycle
Feed and water: Altromin and tap water, ad libitum

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

100, 50 and 25% (25 µL to the dorsum of each ear)
The pre-screen test was performed using dose of 100 % (v/v). Based on the observations recorded in the preliminary test, the concentration of 100 % was selected as top dose for the main test.

No. of animals per dose:

5

Details on study design:

Main study
Day 1: each animal was identified and the body weight was recorded. To the dorsum of each ear 25µL of the appropriate dilution of the test substance, or the vehicle alone was applied.
Days 2 and 3: the application procedure carried out on day 1 was repeated.
Days 4 and 5: no treatment.
Day 6: The body weight of each animal was recorded. 250µL of phosphate-buffered saline (PBS) containing 2 µCi (7.4 x 104 Bq) of 125I-iododeoxyuridine and 10E-05M fluorodeoxyuridine was injected into all test and control mice via the tail vein. Five hours later, the animals were killed. The draining auricular lymph nodes from each ear were excised and pooled in PBS for each experimental group (pooled treatment group approach).
Cell suspension of lymph node cells from pooled treatment groups was prepared and the cellular proliferation was determined (incorporated radioactivity).
Erythema scores and ear thickness were recorded as well.

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Key result

Parameter:

SI

Value:

ca. 2.24

Test group / Remarks:

at 25% concentration

Remarks on result:

other: SI <3

Key result

Parameter:

SI

Value:

ca. 3.93

Test group / Remarks:

at 50% test concentration

Remarks on result:

other: SI >3

Key result

Parameter:

SI

Value:

ca. 4.38

Test group / Remarks:

at 100% concentration

Remarks on result:

other: SI >3

Key result

Parameter:

EC3

Value:

ca. 36.25

Remarks on result:

other: moderate skin sensitiser

Cellular proliferation data / Observations:

Lymph Node Proliferation:
In comparison with the control group, an increase of the pooled lymph node weights was recorded in all tested concentrations. This increase was dose dependent. The pooled lymph node weights of treated groups were 0.0371g for 25% concentration, 0.0400g for 50% concentration and 0.0574g for 100% concentration of tested substance. The lymph node weight of control group and positive control group were 0.0284g and 0.0663g, respectively. The DPM values for the three treated groups were 2228 (25%), 3899 (50%) and 4345 (100%), respectively. The SI values for the three treated groups were 2.24 (25%), 3.93 (50%) and 4.38 (100%), respectively. The calculated EC3 value was 36.25%. After application of the test substance at three concentrations (25%, 50% and 100%) animals did not show visible clinical symptoms or local irritation or systemic toxicity.
From the results of this study, the test substance was considered as a potential skin sensitizer in the murine local lymph node assay and should be classified as Skin Sensitizer Category 1B according to EC 1272/2008 on classification, labeling and packaging.

No marked changes of mean body weight were observed during the study.

Interpretation of results:

other: category 1B - as per CLP criteria

Conclusions:

Under the study conditions, the test substance was considered as a skin sensitizer in the murine local lymph node assay.

Executive summary:

A study was conducted to determine the skin sensitisation potential of the test substance according to OECD Guideline 429 (LLNA), in compliance with GLP.Three groups of 5 female CBA/J mice were treated at concentrations of 25, 50 and 100% w/w on three consecutive days by open application on the ears. Five control animals each were similarly treated, but with vehicle alone (acetone/olive oil, 4:1, v/v; negative control) and α-hexylcinnamaldehyde (positive control).Lymphocyte proliferation was measured using incorporation of radioactive 125I-iododeoxyuridine and 10E-05M fluorodeoxyuridine in the draining lymph nodes. The radioactive incorporation was expressed as disintegrations per minute (DPM)/pooled treatment group and compared with DPM values from the vehicle control group and expressed as the Stimulation Index (SI). Animals were also carefully observed once daily for any clinical symptoms, either of local irritation at the application site or of systemic toxicity. The body weight was recorded as well. In comparison with the control group, a dose dependent increase of the pooled lymph node weights was recorded in all tested concentrations. The pooled lymph node weights of treated groups were determined to be 0.0371g for 25% concentration, 0.0400g for 50% concentration and 0.0574g for 100% concentration of tested substance. The lymph node weight of control group and positive control group was 0.0284g and 0.0663g, respectively. The DPM values for the three treated groups were 2228 (25%), 3899 (50%) and 4345 (100%), respectively. The SI values for the three treated groups were 2.24 (25%), 3.93 (50%) and 4.38 (100%), respectively. The calculated EC3 value was 36.25%. The values for the negative and positive controls were in the expected ranges and the experiment was considered valid. The treated animals however did not show visible clinical symptoms or local irritation or systemic toxicity. The body weights and body weight gain of experimental animals remained in the same range as controls over the study period. Under the study conditions, the test substance was considered to be sensitizing to skin (Kochan, 2016).