Mecrilate

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented publication which meets basic scientific principles

Justification for type of information:

Justification: Butylcyanoacrylate (BUCA) is a structural homologue

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1969

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Repeated oral application to weaning rats

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Enbucrilate

EC Number:

229-552-2

EC Name:

Enbucrilate

Cas Number:

6606-65-1

Molecular formula:

C8H11NO2

IUPAC Name:

butyl 2-cyanoacrylate

Test material form:

other: polymer powder

Details on test material:

- n-butyl cyanoacrylate (CAS 6606-65-1)
- density 0.989 g/mL
- used as polymerized powder (preparation procedure see "any other information on materials and methods")

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

ANIMALS: 49 weaning rats, 26 females and 23 males
FEEDING: rat standard food
WATER: ad libitum

Administration / exposure

Route of administration:

oral: feed

Vehicle:

other: 10 g of rat standard food

Analytical verification of doses or concentrations:

no

Details on mating procedure:

not applicable

Duration of treatment / exposure:

10 d

Frequency of treatment:

daily

Duration of test:

10 d

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

400 other: mg

Remarks:

in 10 g standard feed

Doses / concentrations 2

Dose / conc.:

800 other: mg

Remarks:

in 10 g standard feed

Doses / concentrations 3

Dose / conc.:

1 600 other: mg

Remarks:

in 10 g standard feed

Doses / concentrations 4

Dose / conc.:

3 200 other: mg

Remarks:

in 10 g standard feed

Doses / concentrations 5

Dose / conc.:

6 400 other: mg

Remarks:

in 10 g standard feed

No. of animals per sex per dose:

see "any other information on materials and methods"

Control animals:

yes, plain diet

Details on study design:

10 day oral application to weaning rats

Examinations

Maternal examinations:

not applicable

Ovaries and uterine content:

no

Fetal examinations:

not applicable

Statistics:

no data

Indices:

not applicable

Historical control data:

no data

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:not examined. Remark: not applicable

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Remarks on result:

not determinable

Remarks:

no NOAEL identified

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:not examined. Remark: not applicable

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

All of the food was eaten each day by all of the rats, except in occasional cases where small amounts of food (including cyanoacrylate) remained.

None of the animals died during the course of the study.

Four rats - one male rat from groups B and C and one female rat from groups D and F - were lost during the course of the study and therefore were not included in the data. As noted in Table I, one male rat in Group 0 and one female rat in Group F were not included in the data. The male rat gained less weight than the average of all the male rats studied, while the female rat gained more weight than the average of all the female rats studied. The weights of each of these two rats were more than three standard deviations from the average weights of all rats of that sex and group. Because of this, these two mavericks were not included in the results.

There were no significant differences in the average weights of any of the experimental groups from the control groups for each sex. In the gross and histologic evaluation of the organs and tissues of all the rats, no abnormalities were found to suggest any systemic toxic changes resulting from the ingestion of cyanoacrylate at 0 or 90 days following ingestion of cyanoacrylate polymer powder.

Applicant's summary and conclusion

Conclusions:

There was no significant effect on the average weights of any of the experimental groups from the control groups for each sex of weaning rats. There were no gross and histologic toxic effects resulting from the ingestion of cyanoacrylate at 0 or 90 days following ingestion of cyanoacrylate polymer powder.

Executive summary:

Of six groups of weaning rats, five groups were fed varying levels of BCA polymer powder for 10 days. The rats' weights were evaluated during the ingestion period and for 90 days following ingestion, at which time the animals were killed and examined grossly and microscopically.

The results indicated that in rats, even with very high dosage levels of cyanoacrylate ingestion,

- no lethal dose level was obtained,

- the weight gains of the experimental groups were statistically no different from those of the control group,

- and there were no gross or histologic toxic effects from this ingested cyanoacrylate.