Considerations for the optimization of in vitro models of chloropicrin toxicity.
Arch Toxicol
; 97(1): 255-261, 2023 01.
Article
in En
| MEDLINE
| ID: mdl-36329301
ABSTRACT
Chloropicrin (CP) is a common agricultural fumigant historically used as a chemical warfare agent and is a concern for potential use in warfare and terrorist applications. Our inability to effectively treat CP-induced injuries makes it essential to better understand CP toxicity. We set out to elucidate variables that must be understood to achieve optimal exposure conditions for in vitro investigations given that such models are important for the study of CP injury and potential therapeutics. To this end, we evaluated the effects of volatility, cell seeding density, and serum concentration of cell culture medium on CP toxicity in an immortalized human corneal epithelial cell line. We found that even with very dilute solutions, CP remained highly volatile, so much so that a 0.0019% CP solution resulted in 90% cell death at time 0, but was nearly nontoxic 45 min later. Not surprisingly, the CP-induced IL-8 response was shown to vary with cell viability in this experiment. After exposure with 0.00115% CP, cells that were 12% confluent experienced over 40% more cell death than cells exposed at 87% confluency. Exposure with the same CP dose in medium containing concentrations of fetal bovine serum (FBS) ranging from 0.1% to 15% exhibited a 17% difference in cell viability. Given that chemical toxicity can be significantly influenced by volatility, cell density, and serum content of cell culture medium, these phenomena should be explored during the development and optimization of toxicant exposure models.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Chemical Warfare Agents
/
Hydrocarbons, Chlorinated
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Arch Toxicol
Year:
2023
Document type:
Article
Affiliation country:
United States