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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
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:
Teratogenic evaluation of lead compounds in mice and rats
Author:
Kennedy, G.L., Arnold, D.W., Calandra, J.C.
Year:
1975
Bibliographic source:
Food Cosmet. Toxicol. Vol 13, pp 629-632

Materials and methods

Principles of method if other than guideline:
Groups of pregnant albino mice and rats were treated by gavage with doses upto 10 mg TEL/kg. TEL was administered daily during the period of rapid organogenesis (days 5-15 of pregnancy for mice and days 6-16 for rats). Single intragastric oral doses were given to groups of 5-20 animals to determine 14 day LD50 values as well
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
Tetraethyllead
EC Number:
201-075-4
EC Name:
Tetraethyllead
Cas Number:
78-00-2
Molecular formula:
C8H20Pb
IUPAC Name:
tetraethylplumbane

Test animals

Species:
mouse
Strain:
CD-1
Details on test animals or test system and environmental conditions:
Sex: female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Remarks:
TEL dissolved, in corn oil , food and water
Duration of treatment / exposure:
5 - 15 Gestational days
Frequency of treatment:
Daily
Duration of test:
18 days
No. of animals per sex per dose:
5 - 20 animals per group
Control animals:
yes, concurrent vehicle

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Medium dose: maternal toxicity (body weight increase reduced by 25%),

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:yes. Remark: at 1 mg/kg bw/day

Effect levels (maternal animals)

Dose descriptor:
LOAEL
Effect level:
1 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
body weight and weight gain

Results (fetuses)

Reduction in number of live offspring:
effects observed, treatment-related
Description (incidence and severity):
Medium dose: reduced number of viable foetuses, and total number
Changes in litter size and weights:
effects observed, treatment-related
Description (incidence and severity):
Medium dose: reduced number of viable foetuses, and total number
Skeletal malformations:
effects observed, treatment-related
Description (incidence and severity):
Medium dose: Delayed skeletal formation
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
ca. 1 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
fetal/pup body weight changes
changes in litter size and weights
skeletal malformations

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

Low dose / medium-dose: No effects on dams, no effects foetotoxic.

 

Medium dose: maternal toxicity (body weight increase reduced by 25%), increased resorption, reduced number of viable foetuses, and total number. Delayed skeletal formation

 

High dose: maternal toxicity (body weight reduced, hypoactivity, tremors, convulsions). Only 25% pregnancy rate, delayed skeletal development, in many animals uterus filledwith a brown liquid with no recognizable foetal tissue. Aborted at high dose treatment after 3 days

Applicant's summary and conclusion

Conclusions:
Maternal toxicity was observed and foetal resorption and general retardation of development was encountered at the higher dose levels. It is concluded that lead as TEL is not teratogenic to the mouse or rat.

NOAEL of < 1 mg/kg bw/day (actual dose received) observed. At doses above 1 mg/kg bw various maternotoxic effects are reported
Executive summary:

Maternal toxicity was observed and foetal resorption and general retardation of development was encountered at the higher dose levels. TEL did not cause any congenital malformations. Foetuses derived from lead exposed females were examined grossly and for internal structural and skeletal development but no teratogenic response was evident, even at dose levels at which signs of maternal toxicity were observed. It is concluded that lead as TEL is not teratogenic to the mouse or rat.

Low dose / medium-dose: No effects on dams, no effects foetotoxic.

 

Medium dose: maternal toxicity (body weight increase reduced by 25%), increased resorption, reduced number of viable foetuses, and total number. Delayed skeletal formation

 

High dose: maternal toxicity (body weight reduced, hypoactivity, tremors, convulsions). Only 25% pregnancy rate, delayed skeletal development, in many animals uterus filledwith a brown liquid with no recognizable foetal tissue. Aborted at high dose treatment after 3 days