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Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
sub-chronic toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Inhalation of tetramethyllead and tetraethyllead
Author:
Davis, R.K., Horton, A.W., Larson, E.E., Stemmer, K.L.
Year:
1963
Bibliographic source:
Archives of Environmental Health Vol 6, pp 473-479

Materials and methods

Principles of method if other than guideline:
In a series of experiments, rats and dogs inhaled various concentrations of TEL according to an intermittent schedule of hours and days. The animals were oberved for 35 weeks for evidence of toxic responses
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
other: CFN
Sex:
male/female
Details on test animals and environmental conditions:
Rats were confined in 32 litre glass cages, 5 animals per group

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
not specified
Vehicle:
not specified
Details on inhalation exposure:
150 x 7 hours at 0 and 12 mg/m3
14 x 7 hours at 22 mg/m3
5 x 7 hours at 46 mg/m3
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
max. 35 Weeks
Frequency of treatment:
150 x 7 hours at 0 and 12 mg/m3
14 x 7 hours at 22 mg/m3
5 x 7 hours at 46 mg/m3
Doses / concentrationsopen allclose all
Dose / conc.:
12 mg/m³ air
Dose / conc.:
22 mg/m³ air
Dose / conc.:
46 mg/m³ air
No. of animals per sex per dose:
5 per group
Control animals:
yes, concurrent vehicle

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
0 mg/m3 (m: 0/10; f: 0/10), 12 mg/m3 (m: 0/5; f: 0/5), 22 mg/m3 (m: 4/5; f: 5/5), 46 mg/m3 (3/5; f: 5/5)
Mortality:
mortality observed, treatment-related
Description (incidence):
0 mg/m3 (m: 0/10; f: 0/10), 12 mg/m3 (m: 0/5; f: 0/5), 22 mg/m3 (m: 4/5; f: 5/5), 46 mg/m3 (3/5; f: 5/5)
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Behaviour (functional findings):
effects observed, treatment-related
Description (incidence and severity):
behavioral disorders, convulsions, coma (n) on the dose, concentration of lead in the brain 10 ug / g
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
vacuolar degeneration and necrosis of cells in the CNS, swollen hepatocytes and Kupffer cells, swelling and necrosis of the proximal and distal renal tubulli, edema, hemorrhages, and inflammations of the lung (n / dose)

Effect levels

open allclose all
Dose descriptor:
NOEL
Effect level:
> 12 mg/m³ air
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
mortality
Dose descriptor:
LOAEC
Effect level:
ca. 22 mg/m³ air
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
mortality

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
An NOEL of greater than 12 mg/m³ air was reported and a LD100 value of 22 mg/m3 quoted
Executive summary:

Results very similar to those observed with dogs are reported by Davis et al.

An NOEL of greater than 12 mg/m³ air was reported and a LD100 value of 22 mg/m3 quoted