2,2'-ethylenedioxydiethyl dimethacrylate

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Remarks:

DATA QUALITY: Study was conducted in accordance with a recognized scientific procedure for determining the developmental toxicity of a test substance when administered repeatedly via inhalation. Study was conducted incompliance with GLP regulations. The study meets national and international scientific standards (OECD 414) and provides sufficient information to support the conclusions regarding the NOAEL and the LOAEL demonstrated from the study data.

Data source

Reference

Reference Type:

publication

Title:

Developmental Toxicities of Methacrylic Acid, Ethyl Methacrylate, n-Butyl Methacrylate, and Allyl Methacrylate in Rats following Inhalation Exposure.

Author:

Saillenfait AM, Bonnet P, Gallissot F, Peltier A, Fabriès

Year:

1999

Bibliographic source:

Toxicological Sciences 50: 136-145

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Methacrylic acid

EC Number:

201-204-4

EC Name:

Methacrylic acid

Cas Number:

79-41-4

Molecular formula:

C4H6O2

IUPAC Name:

2-methylprop-2-enoic acid

Details on test material:

Methacrylic acid (CAS: 79-41-4)
Purity: 98 %
Obtained from Fluka Chemie AG

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

Nulliparous female Sprague-Dawley rats, weighing 180-200  grams.obtained from IFFA Credo Breeding Labs. AGE at Start of Test: sexually mature females; age not specified. Mated females were  housed inclear polycarbonate cages with stainless steel wire lids and  hardwood shavings for bedding. Food and water available adlibitum except  during exposures.

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure (if applicable):

whole body

Vehicle:

unchanged (no vehicle)

Details on exposure:

 Exposures were whole  body and conducted in a 200 L chamber. Chamber temperature was 23 degrees  C, and the relative humidity was 50%. Air was passed through a heated  bubbler containing test material. The vaporized material was then  introduced into the exposure chambers.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

 Concentrations were monitored  continuously with a GC, and were determined once during each 6 hr  exposure by collecting the material and analyzing against a standard  using GC.   

Details on mating procedure:

2-3 females were caged with one male rat for mating. The  onset of gestation was based upon the presence of sperm in the vaginal  smear and this was designated gestation day 0. After confirmation of  mating, females werere turned to an individual cage. 

Duration of treatment / exposure:

6 hours per day

Frequency of treatment:

day 6 to 20 of gestation

Duration of test:

Mated females were exposed 6 hr/day on days 6 through  20 of gestation.

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

50 ppm

Remarks:

corresponds to 179 mg/m3

Doses / concentrations 2

Dose / conc.:

100 ppm

Remarks:

corresponds to 358 mg/m3

Doses / concentrations 3

Dose / conc.:

200 ppm

Remarks:

corresponds to 716 mg/m3

Doses / concentrations 4

Dose / conc.:

300 ppm

Remarks:

corresponds to 1076 mg/m3

No. of animals per sex per dose:

22-25 pregnant females per dose.

Control animals:

other: yes, concurrently to filtered room air

Examinations

Ovaries and uterine content:

 The uterus was removed and weighed. At necropsy, the uterine horns and ovaries were exposed  to count the C.L., implantation sites, resorption sites, and viable and  dead fetuses.   FERTILITY AND REPRODUCTIVE PERFORMANCE: The following data were recorded  for each group of numbers of CL, and implantation sites o number of  resorptions and viable and dead fetuses. O mean fetal body weights o  fetuses examined for gross malformations and skeletal abnormalities of  sex and of fetuses.

Fetal examinations:

Live fetuses were weighed, sexed, and examined for external  anomalies. 50% of the live fetuses were preserved in Bouin's solutionand  examined for internal soft-tissue changes. The remaining fetuses were  fixed in ethanol (70%), eviscerated and then processed for skeletal  staining with alizarin red S.

Statistics:

 The number of CL, implantation sites,and live  fetuses, maternal food consumption and various body weights were analyzed  by ANOVA, followed by Dunnett'st-test. the percentage of non-live  implant, resorptions,and males and the proportion of fetuses with  alterations ineach litter were evaluated by Kruskal-Walles test followed  by Dixon-Massey test. Rates of pregnancy and percentage of litters with  any malformations or external, visceral, or skeletal variations were  analyzed using Fisher's test. Where appropriate, least squares analysis  was performed. The level of significance was p < 0.05.

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:

not specified

Dermal irritation (if dermal study):

not specified

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Absolute weight gain was significantly reduced at 300 ppm.

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

Fopod consumption was reduced at 300 ppm.

Food efficiency:

not specified

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

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Maternal developmental toxicity

Number of abortions:

no effects observed

Pre- and post-implantation loss:

no effects observed

Total litter losses by resorption:

no effects observed

Early or late resorptions:

no effects observed

Dead fetuses:

no effects observed

Changes in pregnancy duration:

not specified

Description (incidence and severity):

Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not specified

Changes in number of pregnant:

no effects observed

Other effects:

not specified

Details on maternal toxic effects:

Maternal toxic effects:yes

Details on maternal toxic effects:
All animals survived the exposure. Exposure to 300 ppm led to significant decreases in maternal weight gain and food consumption throughout exposure. Absolute weight gain was significantly reduced at 300 ppm.

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Effect level:

200 ppm

Based on:

test mat.

Basis for effect level:

body weight and weight gain

Remarks on result:

other: corresponds to 716 mg/m³

Maternal abnormalities

Abnormalities:

effects observed, treatment-related

Localisation:

other: unspecific (body weight)

Results (fetuses)

Fetal body weight changes:

no effects observed

Description (incidence and severity):

Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): no effects observed

Reduction in number of live offspring:

not specified

Changes in sex ratio:

no effects observed

Changes in litter size and weights:

not specified

Changes in postnatal survival:

not specified

External malformations:

no effects observed

Skeletal malformations:

no effects observed

Visceral malformations:

no effects observed

Other effects:

not specified

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
There were no significant changes in number of implantations and live fetuses, in the incidence of non-live implants and sorptions, or in fetal weights across groups. One fetus of 200 ppm and two of the 300 ppm group showed different types of malfomations. There was no consistent pattern of changes to suggest any treatment-related effects. The difference of fetuses with external, visceral, and skeletal variations did not differ between the control and the treated groups. No significant increase in embryo/fetal lethality or fetal malformations were observed after exposure to methacrylic acid. While maternal toxicity was observed, methacrylic acid caused no  evidence of developmental toxicity up to 300 ppm.

Effect levels (fetuses)

Dose descriptor:

NOAEL

Effect level:

>= 300 ppm

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no effects observed

Remarks on result:

other: corresponds to 1076 mg/m³

Fetal abnormalities

Abnormalities:

no effects observed

Overall developmental toxicity

Developmental effects observed:

no

Applicant's summary and conclusion

Conclusions:

Using a valid scientific method, no significant increase in embryo/fetal lethality or fetal malformations were observed after exposure to methacrylic acid. While maternal toxicity was observed, methacrylic acid caused no  evidence of developmental toxicity up to 300 ppm.

Executive summary:

In an OECD 414 prenatal developmental toxicity study using whole body inhalation methacrylic acid produced no embryo - or foetal lethality, nor fetal malformations after exposure with methacrylic acid, despite overt maternal toxicity (decreased body weight and feed consumption). The NOEC (teratogenicity) was considerd to be 300 ppm (1076 mg/m³).

NOTE: Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.