Teratogenicity of asbestos in mice

Our plain-English summary of Teratogenicity of asbestos in mice, by T. Fujitani, M. Hojo, A. Inomata, et al (The Journal of Toxicological Sciences, 2014).

The study

• Authors: T. Fujitani, M. Hojo, A. Inomata, A. Ogata, A. Hirose, T. Nishimura, D. Nakae
• Journal: The Journal of Toxicological Sciences
• Published: 2014;39(2):363-70
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Possible teratogenicity of 3 different asbestos (crocidolite, chrysotile and amosite) was assessed in CD1(ICR) mice. Dams on day 9 of gestation were given a single intraperitoneal administration at dose of 40 mg/kg body weight of asbestos suspended in 2% sodium carboxymethyl cellulose solution in phosphate buffered saline, while dams in the control group were given vehicle (10 ml/kg body weight). Dams and fetuses were examined on day 18 of gestation. To compare with the control group, the mean percentage of live fetuses in implantations in the group given crocidolite and the incidence of dams with early dead fetuses in the groups given chrysotile or amosite were increased. While no external or skeletal malformation was observed in the control group, the incidence of external malformation (mainly reduction deformity of limb) in the group given amosite, and the incidences of skeletal malformation (mainly fusion of vertebrae) in the all dosed groups were significantly increased. The result indicated that asbestos (crocidolite, chrysotile and amosite) have fetotoxicity and teratogenicity in mice.

In plain English

This was an experiment in pregnant mice of the CD1(ICR) strain. On day 9 of pregnancy, the mice received a single injection into the abdominal cavity of 40 mg/kg body weight of crocidolite, chrysotile or amosite asbestos. Control mice received only the suspending liquid. Mothers and fetuses were examined on day 18. Mothers given chrysotile or amosite were significantly more likely to have early dead fetuses (8 of 9 and 8 of 10 mothers, against 1 of 9 controls). In the crocidolite group, the share of implantations that were live fetuses was significantly lower (64% against 99%). No external or skeletal malformations were seen in the 130 control fetuses. External malformations, mainly missing fingers or forelimbs, were significantly increased only with amosite (5 of 116 fetuses). Skeletal malformations, mainly fused vertebrae, were significantly increased in all three asbestos groups (6 of 92, 5 of 93 and 13 of 116 fetuses, against 0 of 130 controls). The authors concluded that these three asbestos types showed fetotoxicity and teratogenicity (harm to fetuses and birth defects) in mice. They said other exposure routes, such as intratracheal or oral, might need further study.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal experiment: pregnant mice given a single intraperitoneal (abdominal cavity) injection of asbestos, compared with a vehicle-only control group
• Who was studied: Pregnant female Crlj: CD1(ICR) mice from Charles River Japan. 10 mice were mated per group; 9 control, 10 crocidolite, 9 chrysotile and 10 amosite mice were pregnant and examined. Fetuses examined for external and skeletal malformations: 130 control, 92 crocidolite, 93 chrysotile, 116 amosite.
• Exposure: UICC reference samples of crocidolite, chrysotile and amosite, autoclaved and suspended in 2% sodium carboxymethyl cellulose in phosphate buffered saline. Given as a single intraperitoneal dose of 40 mg/kg body weight on day 9 of gestation. Controls received the vehicle only.
• Main results:
  • Mothers with early dead fetuses were significantly increased in the chrysotile group (8/9) and the amosite group (8/10) compared with controls (1/9). The crocidolite group (5/10) was not marked as significant.
  • In the crocidolite group, the percentage of implantation sites with live fetuses was significantly lower than in controls (64 ± 36% vs 99 ± 3%).
  • No external or skeletal malformations were observed in control fetuses (0/130 for each). Fetuses were examined for external and skeletal anomalies; internal organs were not reported as examined for malformations.
  • External malformations were significantly increased only in the amosite group: 4/10 litters (40%) and 5/116 fetuses, against 0/9 litters and 0/130 fetuses in controls. These included reduction deformity of limb (4 fetuses), cleft face, omphalocele, absent genital tubercle and absent tail.
  • One limb reduction deformity (lack of a finger) in the crocidolite group and one open eyelid in the chrysotile group were not statistically significant increases.
  • Fetuses with skeletal malformations were significantly increased in all asbestos groups compared with controls: 6/92 crocidolite, 5/93 chrysotile and 13/116 amosite, against 0/130 controls. Fusion of vertebral body and arch was the main finding (5, 5 and 9 fetuses). Litters with skeletal malformations were significantly increased for chrysotile (4/9) and amosite (7/10) but not crocidolite (3/10).
  • The body weight of live fetuses was not changed by asbestos.
  • No mothers died. In mothers given crocidolite or amosite, total white blood cell and neutrophil counts were significantly higher than in controls, and liver and spleen weights were also higher. Spleen weights were 422 ± 206 mg for crocidolite and 418 ± 126 mg for amosite, against 137 ± 20 mg in controls.
• The authors' conclusion: The authors concluded that crocidolite, chrysotile and amosite showed fetotoxicity and teratogenicity in mice.
• Limitations the authors state:
  • The authors said further study by other routes of administration, such as intratracheal or oral, may be needed to clarify a non-hazardous dose for humans.
  • The authors stated that the relation between the immune changes seen in the mothers and the defects in embryo development is unclear.
  • Only one dose was tested. The authors reported that a preliminary study at 4 mg/kg showed no adverse effects on mothers or fetuses, and that the dose-dependent profile was still being assessed.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Amosite, Chrysotile, Crocidolite.

Medical terms in this study, explained in our Lexicon: Crocidolite, Chrysotile, Amosite.

Related studies

• Asbestos in organs and placenta of five stillborn infants suggests transplacental transfer — A.K. Haque, M.G. Mancuso, et al. (1992)
• Chrysotile asbestos fibers detected in the newborn pups following gavage feeding of pregnant mice — A.K. Haque, I. Ali, et al. (2001)
• Effects of sustained stimulation with multi-wall carbon nanotubes on immune and inflammatory responses in mice — A. Yamaguchi, T. Fujitani, et al. (2012)
• MicroRNA expression in lung tissues of asbestos-exposed mice: Upregulation of miR-21 and downregulation of tumor suppressor genes Pdcd4 and Reck — Y. Hiraku, J. Watanabe, et al. (2021)
• Placental transfer of asbestos — H.M. Cunningham, R.D. Pontefract (1974)
• Asbestos surface provides a niche for oxidative modification — H. Nagai, T. Ishihara, et al. (2011)

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