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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Relatively well described study with relevant endpoints and significant statistical material. Limited description of analytical section but references to studies are provided

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1975

Materials and methods

Principles of method if other than guideline:
Intratracheal administation of BeO to rats and impact of reproduction and onset of beryllium disease
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Reference substance name:
Automatically generated during migration to IUCLID 6, no data available
IUPAC Name:
Automatically generated during migration to IUCLID 6, no data available
Details on test material:
Radioactively labelled BeO (7BeO) calcined at either 960 °C or 500 °C.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Details on test animals or test system and environmental conditions:
Rats weighed between 150-200 g. Standard rat food was available during the study. Animals were weighed weekly.
Animals number:
First study: 120 females and 30 males
Second study: 40 females and 16 males

Administration / exposure

Route of administration:
intratracheal
Vehicle:
physiological saline
Details on exposure:
First study: 0.2 mg 7BeO in 0.2 ml
Second study: same dose and volume as first study
Analytical verification of doses or concentrations:
no
Details on mating procedure:
Half of the females in each group were placed with males.; 4-5F and 2M per cage.
Duration of treatment / exposure:
Single exposure
Frequency of treatment:
Single exposure
Duration of test:
Final sacrifice 15 months after exposure
No. of animals per sex per dose:
BeO
Study 1: 80F and 15M
Study 2: 20F and 8M
An equivalent number of animals received saline only.
Details on study design:
The number of dead and live pups were counted and the lactation index calculated. Animals were sacrificed at certain timepoints and tissues were taken for histological examination. Additionally, serum activity of alkaline phosphatase, isocitric dehydrogenase, glutamic pyruvic transaminase, lactic dehydrogenase, and concentration of serum calcium, cholesterol, glucose were determined.

Examinations

Maternal examinations:
Body weight
Ovaries and uterine content:
No information
Fetal examinations:
Whole fetus counted for 7BeO.
Statistics:
Fischer-Baron test for statistical comparisons
Indices:
Lactation index
Historical control data:
No information

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:yes

Details on maternal toxic effects:
Lung lesions including bronchial mucosal hyperplasia and granulomata. Pregnancy had no effect on severity or time of onset. Renal calcificiation was also observed.

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
Teratogenic effects not properly assessed. Bodyweight of pups were not affected by maternal BeO exposure.No effects on reproductive parameters was observed except a slight increase in number of live pups and number of litters per female in Be exposed animals.

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

Concentration of Be in tissue was highest in lung. There was no significant effect of BeO on the biochemical parameters studied.

Table 1 Effect on reproductive parameters

Study 1  # females # pregnancies/female  #live pups/litter  #dead pups/litter  #live pups per female  Lactation index  Weight per pup 
12 mo sacrifice: Be  5  4.6+/-0.7 10.0+/- 0.7  0.3  46.0+/-10.7 93.5  38.0 
12 mo sacrifice: Saline  4  3.5+/-0.6 9.9+/- 0.9  0.7  34.8+/-9.1 86.3  39.7 
15 mo sacrifice: Be  8  7.3+/-0.7 9.4+/-0.5 0.6  68.5+/- 7.7  82.9  40.6 
15 mo sacrifice: Saline  4  4.3+/-0.6 10.2+/-  0.9 0.8  43.5+/-7.9 83.3  39.8 
 Study 2                     
 Be  10  4.6+/-0.7  9.4+/-0.6  0.8  43.2+/-8.6  54.1  41.9
 Saline  10  4.0+/-0.5  7.1+/-0.6  0.9  27.8+/-5.7  80.0  42.3

Applicant's summary and conclusion

Conclusions:
The most significant observation in this study was the confirmation of lung granulomas in animals exposed to BeO. The other effects of BeO in this study is relatively modest and of relatively little relevance to humans. No effect on reproductive effects or onset of Beryllium disease were seen.
Executive summary:

Male and female rats were administered radioactively labeled BeO. The animals were given a single dose of BeO via the intratracheal route. The animals were then allowed to breed repeatedly and then killed at various timepoints. Lung histology, level of Be in different tissues and various biochemical parameters were then assessed. Additionally, reproductive parameters were also assessed.

Lung lesions were observed in exposed animals. These were limited to granulomata and bronchial mucosal hyperplasia. Pregnancies had no effect on the onset or severity of these lesions. Renal calcification was also observed in some animals. No significant effect on reproductive parameters were seen.