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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:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: secondary literature

Data source

Reference
Reference Type:
publication
Title:
A rat teratology study with Tetrathal (tetrachlorophthalic anhydride)
Author:
Nair RS, Johannsen FR, Levinskas GJ, Schroeder RE
Year:
1984
Bibliographic source:
Federation Proceedings 43, 365

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Principles of method if other than guideline:
Pregnant Sprague-Dawley rats (24 mated females/dose) were administered Tetrachlorophthalic anhydride (CASRN 117-08-8) in corn oil via gavage at 0, 250, 1000 or 2000 mg/kg-bw/day during gestation days 6 – 19.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
14 days (gestation day 6 to 19)
Frequency of treatment:
once daily
Duration of test:
animals were killed on day 20
No. of animals per sex per dose:
24 females/dose
Control animals:
yes, concurrent vehicle

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
2 000 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects. Remark: at 1000 mg/kg bw

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: teratogenicity

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

No treatment-related parental mortality was observed. Lethargy was observed in several adult females soon after dosing at 2000 mg/kgbw/day, as early as gestation day 6. Pale eye color was observed in four adults at 2000 mg/kgbw/day on gestation day 20. Developmental effects were observed at 2000 mg/kg-bw/day and included reduced fetal body weight, a slight increase in the incidence of asymmetric/unossified sternebra and incompletely ossified thoracic vertebral centra and an increase in the incidence of rib and vertebral malformations.

Applicant's summary and conclusion

Executive summary:

Pregnant Sprague-Dawley rats (24 mated females/dose) were administered CASRN 117-08-8 in corn oil via gavage at 0, 250, 1000 or 2000 mg/kg-bw/day during gestation days 6 – 19. Animals were observed twice daily for mortality and abnormal behavior. Clinical observations and body weight were recorded at several intervals throughout the study. On gestation day 20, animals were sacrificed and uterine horns were examined for implantation sites, resorptions and the number of viable or non-viable fetuses. The number of corpora lutea was also recorded. The sex and weights of all live fetuses were recorded and all fetuses were examined for external abnormalities. One half of the fetuses were examined for skeletal malformations and the other half were examined for internal anomalies. No treatment-related parental mortality was observed. Lethargy was observed in several adult females soon after dosing at 2000 mg/kgbw/day, as early as gestation day 6. Pale eye color was observed in four adults at 2000 mg/kgbw/day on gestation day 20. Developmental effects were observed at 2000 mg/kg-bw/day and included reduced fetal body weight, a slight increase in the incidence of asymmetric/unossified sternebra and incompletely ossified thoracic vertebral centra and an increase in the incidence of

rib and vertebral malformations.

NOAEL (maternal toxicity) = 2000 mg/kg-bw/day (highest dose tested)

LOAEL (developmental toxicity) = 2000 mg/kg-bw/day (based on skeletal malformations and

reduced fetal weight)

NOAEL (developmental toxicity) = 1000 mg/kg-bw/day