Beryllium oxide

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well described study with clear aims. Experimental design and analysis seemingly sound.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1990

Materials and methods

Objective of study:

other: clearance, translocation and excretion

Principles of method if other than guideline:

Inhalation of BeO and assessment of clearance, translocation and excretion

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Beryllium oxide

EC Number:

215-133-1

EC Name:

Beryllium oxide

Cas Number:

1304-56-9

Molecular formula:

BeO

IUPAC Name:

oxoberyllium

Details on test material:

Radiolabeled BeO was generated by co-precipitation of 7BeCl with BeC2O4 to form aqueous 7Be(OH)2 which was then nebulized. The aerosol stream was passed through a furnace (500C), particles collected on silver membrane filter. The particles were in turn further calcined at either 500C or 1600C for 16 hours to generate BeO.

Radiolabelling:

yes

Remarks:

(7)Be

Test animals

Species:

dog

Strain:

Beagle

Sex:

male/female

Details on test animals or test system and environmental conditions:

Beagle dogs ranged in age from 20 to 61 months and from 6.2 to 12.2 kg. The animals were housed indoors with outdoor kennel runs. They were observed daily. Food was provided at 350 g per day and water was ad libitum.

Administration / exposure

Route of administration:

inhalation: aerosol

Vehicle:

unchanged (no vehicle)

Details on exposure:

The dogs were exposed to BeO pernasally for 5-42 minutes. The mean concentration of BeO was 28 ug/ L. The control dogs were exposed to nebulized distilled water for 30 minutes.

Duration and frequency of treatment / exposure:

One time exposure for 5-42 minute period.

Doses / concentrations

Remarks:

Doses / Concentrations:
High and low dose; BeO calcined at different temperatures (500 or 1000C) results in lung burdens of 17 and 50 ug/kg bw.

No. of animals per sex per dose / concentration:

n=2 for high dose, n= 7/8

Control animals:

yes, sham-exposed

Details on dosing and sampling:

Excreta was collected continously for the first 21 days followed by 3 day collections at 6, 12, 18, and 24 weeks after exposure. Radioactive whole body-count of each dog was done immediately after exposure and on day 2, 3, 4, 5, 6 and 7 followed by twice weekly for 3 months and then twice monthly.

At the end of the study, animals were sacrificed and subject to a complete necropsy. Beryllium content of tissues were determined. Histopathological examination of lungs, tracheobroncial lymph nodes was performed.

Statistics:

Bonferroni multiple comparison test

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

BeO cleared relatively slowly from the lung. BeO calcined at 500 °C cleared faster than when calcined at 1000 °C.

Details on distribution in tissues:

Most tissues contained levels of Be in the order of a few % of total body burden. The highest levels were found in the skeleton, tracheobroncial lymph nodes, liver, and blood.

Details on excretion:

Feces was the predominant route of excretion at early times and up to 6 months after exposure. Urine became predominant at later timepoints. A greater amount of the BeO calcined at 500 °C was excreted than BeO calcined at 1000 °C.

Any other information on results incl. tables

Table 1 Excretion of Beryllium

BeO calcinationtemperature in °C	Days after exposure	Cumulative excretion (% of initial lung burden)	% of total excretion
			Feces	Urine
500	32	24 +/-6	59 +/-2	41 +/-2
1000	32	18 +/-2	68 +/-3	32 +/-3
500	64	19+/-3	45 +/-6*	55 +/-6*
1000	64	21 +/-1	67 +/-6*	33 +/-6*
500	180	42 +/-8*	47 +/-14	53 +/-14
1000	180	19 +/-4*	54 +/-14	46 +/-14

N= 2 (32 and 64 days), N=4 (180 days)

* p<0.05

Table 2 Beryllium burden in selected tissues

		Lungs	Tracheobronchial lymph nodes	Skeleton	Liver	Blood
500	8	85 +/-6	0.6 +/-0.5	1.4 +/-0.8	0.1 +/-0.1	0.4 +/-0.1
1000	8	97	0.2	0.5	0.04	0.3 +/-0.1
500	32	77 +/-2*	2.1 +/-2.2	2.5 +/-0.1	0.6 +/-0.1	0.4 +/-0.1
1000	32	97 +/-2*	0.9 +/-0.2	0.4 +/-0.1	0.06 +/-0.09	0.2 +/-0.3
500	64	46 +/-8*	8.8 +/-5.9	14 +/-4*	2.3+/-1.0*	1.0 +/-0.3
1000	64	88 +/-8*	1.9 +/-1.1	1.5 +/-0.9*	0.2 +/-0.1*	0.3 +/-0.1
500	180	14 +/-2*	1.8 +/-0.7	16+/-1*	3.6 +/-0.5*	1.6 +/-0.3
1000	180	62 +/-2*	2.1 +/-0.9	3.1 +/-0.5*	0.4+/-0.1*	1.0 +/-0.2

* p<0.05

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): high bioaccumulation potential based on study results
BeO is relatively persistent in the lungs. Calcination temperature affects the clearance rate from lung and body. Beryllium burden in tissues was generally low with levels of Be in skeleton being the highest

Executive summary:

Beagle dogs were exposed to BeO via inhalation. The BeO was calcined at either 500 or 1000 °C. Initial lung burdens of 17 or 50 ug/kg bodyweight was achieved. The levels of BeO in feces and urine was determined. Following sacrifice of animals, the level of BeO in tissues were determined. BeO was persistent in the lungs following inhalative exposure. Translocated BeO was primarily found in skeleteon, tracheobronchial lymph nodes, skeleton, liver and blood. Excretion of BeO was primarily in the feces at early timepoints and urine later (> 6 months). There was an effect of calcination temperature with BeO calcinated at 500C generally being cleared from the lung faster than BeO calcinated at 1000 °C. BeO calcinated at 500 °C was also generally associated with more severe pathological and immunological responses.