Dibutyl hydrogen phosphate

Repeated dose toxicity: other routes

Administrative data

Endpoint:

short-term repeated dose toxicity: other route

Type of information:

experimental study

Reliability:

3 (not reliable)

Data source

Reference

Reference Type:

publication

Title:

Uptake, Accumulation, and Biomarkers of PM2.5-Associated Organophosphate Flame Retardants in C57BL/6 Mice after Chronic Exposure at Real Environmental Concentrations

Author:

Chen M

Bibliographic source:

Environ. Sci. Technol. 2020, 54, 9519−9528

Materials and methods

Principles of method if other than guideline:

no guideline followed

Test animals

Species:

mouse

Administration / exposure

Route of administration:

other: intratracheal

Details on exposure:

20 μL of an OPFR standard solution (mixture of 6 different flame retardants, including tributyl phosphate) or 20 μL 0.9% saline was injected through the mouth into the trachea. The OPFR exposure concentrations are calculated based on the respiratory volume of an adult mouse (30 mL·min−1). Instillation was performed once every three days for 72 days.

Results and discussion

Results of examinations

Details on results:

The mice were randomly divided into four groups, each with eight mice: a control group (C-group), a low OPFR dosage group (L-group, 0.088 μg·kg−1·day−1) whose dosage corresponds approximately to the OPFR concentration observed in PM2.5 samples collected in Guangzhou during winter, a medium dosage group (M-group, 0.88 μg·kg−1·day−1), and a high dosage group (H-group, 8.8 μg·kg−1·day−1). Intratracheal instillation of mice was performed as described previously. Briefly, 20 μL of an OPFR standard solution (mixture of 6 different flame retardants, including tributyl phosphate) or 20 μL 0.9% saline was injected through the mouth into the trachea. The OPFR exposure concentrations are calculated based on the respiratory volume of an adult mouse (30 mL·min−1). Instillation was performed once every three days for 72 days. After 72 days of exposure mice were sacrificed after the final exposure and all samples were stored at −80 °C. The sum of organophosphate flame retardants (OPFR) concentrations in tissues from mice in the medium dosage group decreased in the order of intestine > heart > stomach > testis > kidney > spleen > brain > liver > lung > muscle. Of the OPFRs detected in all three exposure groups, chlorinated alkyl OPFRs were most heavily accumulated in mice. We found a significant positive correlation between the bioaccumulation ratio and octanol−air partition coefficient (KOA) in mice tissues for low log KOW OPFR congeners (log KOW ≤ 4, p < 0.05). Three urinary metabolites (di-p-cresyl phosphate: DCrP, diphenyl phosphate: DPhP, dibutyl phosphate: DnBP) were detected from the high dosage group.
This study is of low relevance for the assessment of di- and tributyl phosphate due to test item being a OPFR mixture, the intratracheal route of exposure, the explorative nature and test system.