Toxicokinetic study following intratracheal instillation or oral gavage of two [7Be]-tagged carbon black samples

Abstract

Background: The toxicokinetic behaviour of nanostructured particles following pulmonary or oral deposition is of great scientific interest. In this toxicokinetic study, following the general principles of OECD TG 417, the systemic availability of carbon black, a nanostructured material consisting of agglomerated aggregates was characterised.

Methods: Each of two grades of beryllium-7 labelled carbon black (Monarch® 1000, oxidized and Printex® 90; untreated) was administered either intratracheally or orally to adult rats. Independent of route, rats received a single dose of approximately 0.3 mg radiolabelled carbon black. A total of 12 rats were treated per grade and per exposure route: 4 females each for feces/urine/organs and serial blood kinetics; 4 males for organs. At necropsy, the complete suite of organs was analysed for females, but only the lungs, liver, kidney, reproductive organs for males.

Results: In the pulmonarily exposed animals, ⁷Be-Monarch® 1000 and ⁷Be-Printex® 90 was detected in feces in the first 3 days after treatment at significant levels, i.e. 17.6% and 8.2%, respectively. In urine, small percentages of 6.7% and 0.4% were observed, respectively. In blood, radioactivity, representative of carbon black was within the background noise of the measurement method. At necropsy, 20 days post-instillation, both test items were practically exclusively found in lungs (75.1% and 91.0%, respectively) and in very small amounts (approximately 0.5%) in the lung-associated lymph nodes (LALN). In the other organs/tissues the test item was not detectable. BAL analyses indicated that carbon black particles were completely engulfed by alveolar macrophages. In orally exposed animals, 98% (⁷Be-Monarch® 1000) and 99% (⁷Be-Printex® 90) of the measured radioactivity was detected in feces. Excretion was complete within the first 3 days following treatment. 1.3% and 0.5% of measured activity was attributable to urine in animals that received ⁷Be-Monarch® 1000 and ⁷Be-Printex® 90, respectively. Radioactivity was absent in blood and other organs and tissues.

Conclusion: Radioactivity, representative of carbon black, was not detected beyond the experimentally defined limit of quantitation systemically after deposition in lungs or stomach in rats. Under these experimental conditions, the two CB samples were not shown to translocate beyond the lung or the GI tract into the blood compartment.

Keywords: 7Be tracer; Carbon black; Intratracheal instillation; Oral gavage; Toxicokinetics.

Fig. 1

Preparation of Monarch® 1000 suspension in 0.01 NaOH–2 min ultrasonic treatment

Fig. 2

Cytospot of BAL macrophages harvested at day 20 post-instillation (⁷Be-Printex.® 90)

Fig. 3

Toxicokinetics of ⁷Be-Monarch.® 1000 after intratracheal instillation. Feces/urine: day 1–3; Lungs/LALN: day 20 following administration. (% refer to the entire radioactivity detected in the rat body: = 100%)

Fig. 4

Toxicokinetics of ⁷Be-Printex.® 90 after intratracheal instillation. Feces/urine: day 1–3; Lungs/LALN: day 20 following administration. (% refer to the entire radioactivity detected in the rat body: = 100%)

Fig. 5

Toxicokinetics of ⁷Be-Monarch.® 1000 after oral gavage. Feces/urine: day 1–3; GI tract day 13 following administration. (% refer to the entire radioactivity detected in the rat body: = 100%)

Fig. 6

Toxicokinetics of ⁷Be-Printex.® 90 after oral gavage. Feces/urine: day 1–3; GI tract day 10 following administration (% refer to the entire radioactivity detected in the rat body: = 100%)