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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

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
other: COBS
Details on test animals 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:
TEL was administered daily during the period of rapid organogenesis (days 6-16 for rats)
Frequency of treatment:
Daily
Duration of test:
20 days
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):
At 1 mg/kg bw/day dose Body weight gain reduced by 70%.

Maternal developmental toxicity

Total litter losses by resorption:
effects observed, treatment-related
Description (incidence and severity):
At 1 mg/kg bw/day dose Increased resorption, reduced number and number of viable fetuses

Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOAEL
Effect level:
0.1 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
body weight and weight gain
Dose descriptor:
LOAEL
Effect level:
1 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
organ weights and organ / body weight ratios
total litter losses by resorption
dead fetuses

Results (fetuses)

Reduction in number of live offspring:
effects observed, treatment-related
Description (incidence and severity):
At 1 mg/kg bw/day dose Increased resorption, reduced number and number of viable fetuses
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Effect levels (fetuses)

Dose descriptor:
LOAEL
Effect level:
1 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
reduction in number of live offspring

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

The low and medium doses showed no effects on mothers and no foetotoxic effects; the medium-high dose was maternotoxic; the high dose was very maternotoxic.

The medium-high dose mothers showed bodyweight growth reduced by 70%. Medium-high dose progeny showed increased resorptions and reduced numbers of both foetuses and viable foetuses.

The high dose mothers showed reduced bodyweight, hypoactivity, temors and convulsions. Only 25% became pregnant, and their foetuses showed delayed skeletal development.  In many animals the uterus became filled with brown fluid, with no foetal tissue discernible. High-dose treatment was discontinued after three 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 reported as 0.1 mg/kg bw/day
LOAEL reported as 1.0 mg/kg bw/day
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.

The low and medium doses showed no effects on mothers and no foetotoxic effects; the medium-high dose was maternotoxic; the high dose was very maternotoxic.

The medium-high dose mothers showed bodyweight growth reduced by 70%. Medium-high dose progeny showed increased resorptions and reduced numbers of both foetuses and viable foetuses.

The high dose mothers showed reduced bodyweight, hypoactivity, temors and convulsions. Only 25% became pregnant, and their foetuses showed delayed skeletal development. In many animals the uterus became filled with brown fluid, with no foetal tissue discernible. High-dose treatment was discontinued after three days.