Allyl 2-cyanoacrylate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2021

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study using OECD testing guideline

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2021

Report date:

2021

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

This study followed the procedures indicated by internal BSL Munich SOPs and the following internationally accepted guidelines and recommendations:
OECD Guidelines for Testing of Chemicals, Section 4, No. 423, “Acute Oral Toxicity – Acute Toxic Class Method” adopted 17 December 2001
Commission Regulation (EC) No. 440/2008, L 142, Annex Part B, Method B.1, tris 30 May 2008
EPA Health Effects Test Guidelines, OPPTS 870.1100 “Acute oral toxicity”, EPA 712-C-02-190, December 2002
Procedures and facilities comply with the requirements of Directive 2010/63/EU and the national legislation defined in the animal protection law concerning the protection of animals used for experimental and other scientific procedures.

GLP compliance:

yes (incl. QA statement)

Remarks:

“Chemicals Act” of the Federal Republic of Germany, Appendix 1 to § 19a as amended and promulgated on October 30, 2020 (BGBl. I S. 2232) “Consensus Document of the National and Länder Working Party on Good Laboratory Practice“

Test type:

acute toxic class method

Test material

Test material information

1

Reference substance name:

Allyl 2-cyanoacrylate

EC Number:

230-796-7

EC Name:

Allyl 2-cyanoacrylate

Cas Number:

7324-02-9

Molecular formula:

C7H7NO2

IUPAC Name:

prop-2-en-1-yl 2-cyanoprop-2-enoate

Test material form:

liquid

Specific details on test material used for the study:

Storage Condition of allyl 2-cyanoacrylate: 2–8 °C, protected from light, since test substance polymerizes very fast upon contact with water or even moisture; contact with water or aqueous materials must be avoided.

The extraction of the test item was performed according to guideline ISO 10993-12.
In total a ratio of 0.2 g of the polymerized test item per mL extraction medium was used.
Extraction conditions: 37 ±1 °C for 72 ± 2 h, under agitation.
Extraction media: physiological saline 0.9% NaCl, B. Braun Melsungen
Step 1: lot no. 20416406, expiry date: 09/2023
Step 2: lot no. 20192410, expiry date: 04/2023
cottonseed oil, Sigma-Aldrich
Step 1: lot no. MKCD7646, expiry date: 13/01/2022
Step 2: lot no. MKCD7646, expiry date: 14/01/2022
The extraction procedure did not reveal any abnormalities in any of the extraction media or the test item. No changes regarding clarity, colour and presence or absence of foreign material in any of the extracts were noted.
The extracts were neither pH-adapted nor filtered, centrifuged, diluted nor changed in any other way before application.
Up to the application within 15 minutes (step 1) or 10 minutes (step 2), the extracts were stored at room temperature.

Test animals

Species:

rat

Strain:

Wistar

Details on test animals or test system and environmental conditions:

Species/strain: healthy rats / WISTAR Crl: WI(Han)
Source: Charles River, 97633 Sulzfeld, Germany
Sex: female (non-pregnant, nulliparous)
Age at the beginning of the study: 8 – 11 weeks old
Body weight at the beginning of the study: Step 1: 165 – 184 g; Step 2: 175 – 199 g
Number of animals: 3 per step / extract, 2 steps per extract were performed (12 animals in total)
The animals were derived from a controlled full-barrier maintained breeding system (SPF). According to the German Act on Animal Welfare the animals were bred for experimental purposes.
This study was performed in an AAALAC-accredited laboratory. According to German animal protection law, the study type has been reviewed and accepted by local authorities. Furthermore, the study has been subjected to Ethical Review Process and was authorised by the Bavarian animal welfare administration.

The animals were randomly selected.
The animals were marked by tail-painting for individual identification.
Prior to the administration a detailed clinical observation of all animals was made. Only healthy animals were used for the test.
Prior to the administration food was withheld from the test animals for approximately 18 hours (access to water was permitted). Following the period of fasting the animals were weighed and the test item was administered. Food was provided again approximately 3 hours post dosing.

Body Weight: Animals were weighed on day 1 (prior to the administration) and on days 2, 3, 4, 8 and 15.

Housing and Feeding Conditions
- Full barrier in an air-conditioned room
- Temperature: 22 ± 3 °C
- Relative humidity: 55 ± 10%
- Artificial light, sequence being 12 hours light, 12 hours dark
- Air change: at least 10 x / hour
- Free access to Altromin 1324 maintenance diet for rats and mice
- Free access to tap water, sulphur acidified to a pH value of approx. 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals)
- The animals were kept in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding
- Certificates of food, water and bedding are filed for two years at BSL Munich and afterwards archived at Eurofins Munich
- Adequate acclimatisation period (at least 5 days) under laboratory conditions

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Each test item extract was administered undiluted at a single dose by gavage using a feeding tube.
Volume of administration: Each test item extract (100% concentration) was administered according to the body weight at a volume of 10 mL/kg bw.

Doses:

In total a ratio of 0.2 g of the polymerized test item per mL extraction medium was used as follows physiological saline 0.9% NaCl 10ml, cottonseed oil 10ml.

No. of animals per sex per dose:

3 per step / extract, 2 steps per extract were performed (12 animals in total)

Control animals:

not specified

Details on study design:

The test for acute toxicity is performed on the rat. Although several mammalian species may be used, the rat has been the preferred rodent species.
It is the principle of the acute toxic class method that, based on a stepwise procedure with the use of a minimum number of animals per step, sufficient information is obtained on the acute toxicity of the test item. Absence or presence of compound-related mortality of the animals dosed at one step will determine the next step.

The animals were observed for 14 days after dosing. A careful clinical examination was made several times on the day of dosing (at least once during the first 30 minutes and with special attention given during the first 4 hours post-dose). Thereafter, the animals were observed for clinical signs once daily until the end of the observation period.
Cageside observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Particular attention was directed to observations of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

No validated in vitro method is available for assessing acute systemic toxicity.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat. (total fraction)

Remarks:

Extracts of the test item were administered. The extraction of the test item was performed according to guideline ISO 10993-12. In total a ratio of 0.2 g of the polymerized test item per mL extraction medium was used.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No mortality (0/6)

Clinical signs:

other: All animals survived throughout the test period without showing any clinical signs of toxicity. The piloerection observed on day 1 in all animals is not considered to be related to the test item but to the administration procedure and the possible stress

Gross pathology:

No specific gross pathological changes were recorded for any animal.

Other findings:

Clinical Signs

Any other information on results incl. tables

 

Clinical Signs Extraction Medium: Physiological Saline 0.9% NaCl

Time of Observation Post-Administration	Step 1	Step 2
0 min – 180 min	nsf	nsf
180 min – 240 min	slight piloerection	slight piloerection
240 min – d 15	nsf	nsf

Clinical Signs Extraction Medium: Cottonseed Oil

Time of Observation Post-Administration	Step 1	Step 2
0 min – 180 min	nsf	nsf
180 min – 240 min	slight piloerection	slight piloerection
240 min – d 15	nsf	nsf

d = study day (study day 1 = day of administration); min = minute(s) post-application; nsf = no specific findings

Step 1, Extraction Medium: Physiological Saline 0.9% NaCl

Day	Animal Number 1	Animal Number 2	Animal Number 3
1	165	167	165
2	176	180	180
3	161	169	175
4	174	188	188
8	184	198	199
15	204	207	205
Weight Gain (Day 1-15) g	39	40	40
Body Weight Change in Comparison to Day 1 (%)	23.6	24	24.2

Step 1, Extraction Medium:Cottonseed Oil

Day	Animal Number 4	Animal Number 5	Animal Number 6
1	184	171	182
2	196	183	196
3	191	185	188
4	190	184	195
8	200	192	210
15	214	198	210
Weight Gain (Day 1-15) (g)	30	27	28
Body Weight Change in Comparison to Day 1 (%)	16.3	15.8	15.4

 

Step 2, Extraction Medium: Physiological Saline 0.9% NaCl

Day	Animal Number 7	Animal Number 8	Animal Number 9
1	199	184	175
2	210	194	192
3	212	195	195
4	213	192	193
8	220	201	196
15	225	210	206
Weight Gain (Day 1-15) (g)	26	26	31
Body Weight Change in Comparison to Day 1 (%)	13.1	14.1	17.1

Step 2, Extraction Medium:Cottonseed Oil

Day	Animal Number 10	Animal Number 11	Animal Number 12
1	190	179	177
2	202	192	189
3	208	196	194
4	210	197	195
8	216	203	195
15	218	210	205
Weight Gain (Day 1-15) (g)	28	31	28
Body Weight Change in Comparison to Day 1 (%)	14.7	17.3	15.8

 

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the present study it can be stated that the test item Allyl 2-cyanoacrylate showed no acute toxic characteristics.