Mecrilate

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1966

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

Deviations:

yes

Remarks:

16 instead of 20 animals/dose group, no information on ophthalmological examination/neurological endpoints

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Mecrilate

EC Number:

205-275-2

EC Name:

Mecrilate

Cas Number:

137-05-3

Molecular formula:

C5H5NO2

IUPAC Name:

methyl 2-cyanoprop-2-enoate

Test material form:

other: polymerised

Details on test material:

Poly (Methyl-2-cyanoacrylate)

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

ANIMALS:
64 healthy weanling albino rats, 32 females and 32 males

HOUSING:
individually in elevated metal cages

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

90 d

Frequency of treatment:

daily

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

50 mg/kg bw/day (nominal)

Remarks:

nominal in diet

Doses / concentrations 2

Dose / conc.:

100 mg/kg bw/day (nominal)

Remarks:

nominal in diet

Doses / concentrations 3

Dose / conc.:

200 mg/kg bw/day (nominal)

Remarks:

nominal in diet

No. of animals per sex per dose:

8

Control animals:

yes, plain diet

Examinations

Observations and examinations performed and frequency:

- observation of symptoms indicating toxic or pharmalogic effects
- weekly body weights
- urine analysis during the study
- hematological values, transaminase, blood urea nitrogen, blood glucose and urinalyses at termination after 90 d

Sacrifice and pathology:

Haematology, urinalysis, histopathology performed after 90 d application

Other examinations:

none

Statistics:

no data

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

see "Any other information on results"

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

see "Any other information on results"

Histopathological findings: neoplastic:

not specified

Effect levels

Key result

Dose descriptor:

NOAEL

Effect level:

> 200 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No statistical significant systemic effects observed

Target system / organ toxicity

Key result

Critical effects observed:

no

Any other information on results incl. tables

RESULTS

Symptomatology:

No untoward indications of toxic or pharmalogic effect were noted over the course of the 90 d experminetal period.

Growth:

Mean weekly body weights, weight ranges and survival data show no statistically significant differences in growth between rats recieving poly (methyl 2-cyanoacrylate) in the diet at different levels, and those in the control group.

Clinical:

Hematological values, transaminase, blood urea nitrogen, blood glucose, and urinalyses were not significantly different between the three test groups and the control group upon termination of the 90 d period. Urine analyses were generally within normal limits, and comparable among both control and test groups during the study.

Histopathology:

The lesion sfound in trachea, lungs and livers were of an infectious nature consistent with the average experience in colony disease. Both control and experimental rats presented similar frequency and severity of lesions, with no sex predominating.

Occurrence of renal pathology was scarce, and more frequent in the controls as a group, except for a rare focus of acute tubulonephritis in one rat on the 100 mg/kg bw/d level of the test agent.

Increases in the terminal ovary weights and respective organ/body weight ratios were recorded in females at all three dose levels.

Other weight and ratio increases included the thyroid in both males and females. These weight changes, when viewed in the light of the negative histopathological and clinical findings, suggest a coincidental statistical phenomenon, although a circumstance of subtle endocrine stress remains plausible.

Applicant's summary and conclusion

Conclusions:

No statistical significant systemic effects induced by oral administration of poly (methyl 2-cyanoacrylate) over a 90 day period to rats. A NOAEL of >200 mg/kg b.w./d was deduced.