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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
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:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Details on test animals 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
Remarks:
Doses / Concentrations:
0, 50, 100, 200 or 300 ppm
Basis:

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

Maternal developmental toxicity

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
Basis for effect level:
other: maternal toxicity

Results (fetuses)

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
Basis for effect level:
other: teratogenicity

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

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).

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