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Developmental toxicity of 1,6-hexamethylene diisocyanate (HDI) in the Sprague-Dawley rat.
Teratology. 2000 Oct; 62(4):205-13.T

Abstract

BACKGROUND

1,6-Hexamethylene diisocyanate (HDI), a widely used chemical in commercial polyurethane manufacture, has been shown to affect the respiratory tract of experimental animals. However, its potential to affect neonatal development, particularly after inhalation exposure, is less well described. The present study was conducted to assess the developmental toxicity of HDI.

METHODS

Gravid Sprague-Dawley rats were exposed to concentrations of 0, 0. 005, 0.050, or 0.300 ppm HDI via inhalation (whole-body exposure) on days 0-19 of gestation. Maternal toxicity, as demonstrated by clinical signs and changes in body weight gain during gestation, was characterized. Dams were sacrificed on gestation day 20, at which time fetuses were removed by cesarean section, the uterus was examined, and a gross maternal necropsy was performed. Maternal evaluation also included lung weight and a detailed histopathologic assessment of the nasal turbinates, larynx, trachea, and lungs. All fetuses were evaluated for external anomalies. Approximately one-half of each litter was examined for visceral effects, the other half underwent a skeletal (bone and cartilage) examination.

RESULTS

Maternal toxicity was demonstrated in the 0.300- and, to a lesser extent, in the 0.050-ppm exposure groups. No maternal effects were noted in the 0.005-ppm group. Test compound-related maternal effects were restricted to histopathological findings and included acanthosis, hyperkeratosis, inflammation of the nasal turbinates, and, more seriously, degeneration of the olfactory epithelium. No pathological alterations were noted in the larynx, trachea, or lungs in any dose group. No test compound-related effects were observed on any reproductive parameters, or any embryonic endpoints, including pre/postimplantation loss and resorption. There were no effects on litter size or the number of fetuses per implantation site and no effects on fetal or placental weights were observed. No test compound-related fetal external, visceral, or skeletal findings were observed. No effect on the fetal or litter incidence of total malformations or variations was observed, and there was no difference in the incidence of malformations between males and females.

CONCLUSIONS

Administered as described in this study, 1, 6-HDI produced maternal effects (nasal turbinate histopathology) at concentrations of 0.050 and 0.300 ppm with no developmental toxicity observed at any concentration.

Authors+Show Affiliations

Bayer Corporation, Agriculture Division, Toxicology Department, Stilwell, Kansas 66085, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10992262

Citation

Astroff, A B., et al. "Developmental Toxicity of 1,6-hexamethylene Diisocyanate (HDI) in the Sprague-Dawley Rat." Teratology, vol. 62, no. 4, 2000, pp. 205-13.
Astroff AB, Sturdivant DW, Lake SG, et al. Developmental toxicity of 1,6-hexamethylene diisocyanate (HDI) in the Sprague-Dawley rat. Teratology. 2000;62(4):205-13.
Astroff, A. B., Sturdivant, D. W., Lake, S. G., Shiotsuka, R. N., Simon, G. S., & Andrews, L. S. (2000). Developmental toxicity of 1,6-hexamethylene diisocyanate (HDI) in the Sprague-Dawley rat. Teratology, 62(4), 205-13.
Astroff AB, et al. Developmental Toxicity of 1,6-hexamethylene Diisocyanate (HDI) in the Sprague-Dawley Rat. Teratology. 2000;62(4):205-13. PubMed PMID: 10992262.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Developmental toxicity of 1,6-hexamethylene diisocyanate (HDI) in the Sprague-Dawley rat. AU - Astroff,A B, AU - Sturdivant,D W, AU - Lake,S G, AU - Shiotsuka,R N, AU - Simon,G S, AU - Andrews,L S, PY - 2000/9/19/pubmed PY - 2001/2/28/medline PY - 2000/9/19/entrez SP - 205 EP - 13 JF - Teratology JO - Teratology VL - 62 IS - 4 N2 - BACKGROUND: 1,6-Hexamethylene diisocyanate (HDI), a widely used chemical in commercial polyurethane manufacture, has been shown to affect the respiratory tract of experimental animals. However, its potential to affect neonatal development, particularly after inhalation exposure, is less well described. The present study was conducted to assess the developmental toxicity of HDI. METHODS: Gravid Sprague-Dawley rats were exposed to concentrations of 0, 0. 005, 0.050, or 0.300 ppm HDI via inhalation (whole-body exposure) on days 0-19 of gestation. Maternal toxicity, as demonstrated by clinical signs and changes in body weight gain during gestation, was characterized. Dams were sacrificed on gestation day 20, at which time fetuses were removed by cesarean section, the uterus was examined, and a gross maternal necropsy was performed. Maternal evaluation also included lung weight and a detailed histopathologic assessment of the nasal turbinates, larynx, trachea, and lungs. All fetuses were evaluated for external anomalies. Approximately one-half of each litter was examined for visceral effects, the other half underwent a skeletal (bone and cartilage) examination. RESULTS: Maternal toxicity was demonstrated in the 0.300- and, to a lesser extent, in the 0.050-ppm exposure groups. No maternal effects were noted in the 0.005-ppm group. Test compound-related maternal effects were restricted to histopathological findings and included acanthosis, hyperkeratosis, inflammation of the nasal turbinates, and, more seriously, degeneration of the olfactory epithelium. No pathological alterations were noted in the larynx, trachea, or lungs in any dose group. No test compound-related effects were observed on any reproductive parameters, or any embryonic endpoints, including pre/postimplantation loss and resorption. There were no effects on litter size or the number of fetuses per implantation site and no effects on fetal or placental weights were observed. No test compound-related fetal external, visceral, or skeletal findings were observed. No effect on the fetal or litter incidence of total malformations or variations was observed, and there was no difference in the incidence of malformations between males and females. CONCLUSIONS: Administered as described in this study, 1, 6-HDI produced maternal effects (nasal turbinate histopathology) at concentrations of 0.050 and 0.300 ppm with no developmental toxicity observed at any concentration. SN - 0040-3709 UR - https://www.unboundmedicine.com/medline/citation/10992262/Developmental_toxicity_of_16_hexamethylene_diisocyanate__HDI__in_the_Sprague_Dawley_rat_ L2 - https://doi.org/10.1002/1096-9926(200010)62:4<205::AID-TERA6>3.0.CO;2-S DB - PRIME DP - Unbound Medicine ER -