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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:
data from handbook or collection of data
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
Cross-reference
Reason / purpose:
read-across: supporting information
Reference
Endpoint:
developmental toxicity
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
Reason / purpose:
read-across source
Related information:
Composition 1
Reference:
Composition 0
Principles of method if other than guideline:
No method details given in review article
GLP compliance:
not specified
Test material information:
Composition 1
Species:
rat
Strain:
Wistar
Details on test animals and environmental conditions:
groups of 20 pregnant rats
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on exposure:
groups of 20 pregnant wistar rats on gestation days 6 to 15
Duration of treatment / exposure:
gestation days 6 to 15
Remarks:
Doses / Concentrations: 5 mg/kg
Basis: actual ingested
Remarks:
Doses / Concentrations: 25 mg/kg
Basis: actual ingested
Remarks:
Doses / Concentrations: 50 mg/kg
Basis: actual ingested
Remarks:
Doses / Concentrations: 500 mg/kg
Basis: actual ingested
No. of animals per sex per dose:
20 pregnant wistar rats/dose
Control animals:
other: Two negative controls; one treated with water, other treated with 0.5% carboxymethylcellulose
Key result
Dose descriptor:
NOAEL
Effect level:
500 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
other: Systemic Toxicity
Key result
Abnormalities:
no effects observed
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects
Key result
Dose descriptor:
NOAEL
Effect level:
500 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Embryotoxicity
Key result
Abnormalities:
no effects observed
Key result
Developmental effects observed:
no

The incidence of fetal malformations in benzoic acid treated rats did not reach statistical significance.

Conclusions:
In a peer reviwed developmental study on the effects of benzoic acid on pregnant rats, the incidence of fetal malformations of treated rats did not reach statistical significance.
Executive summary:

In a peer reviwed developmental study on the effects of benzoic acid on pregnant rats, benzoic acid at doses of 5, 25, 50, and 500 mg/Kg was administered by stomach tube to groups of 20 pregnant Wistar rats on Gestation Days 6-15. Two negative control groups were maintained: one was treated with water, the other with 0.5% carboxymethylcellulose. A positive control group received either thalidomide or aspirin. Dams were killed on Day 21.

 

Maternal survival was similar for treated and control groups. The incidence of fetal malformations did not reach statistical significance (Polish Academy of Sciences, 1977).


Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1977

Materials and methods

Principles of method if other than guideline:
No method details given in review article
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
substance radiolabelled as [Carboxy-14C] benzoic acid
Purity: radiochemical purity, 99%

Test animals

Species:
rat
Strain:
Wistar
Details on test animals and environmental conditions:
groups of 20 pregnant rats

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on exposure:
groups of 20 pregnant wistar rats on gestation days 6 to 15
Duration of treatment / exposure:
gestation days 6 to 15
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations: 5 mg/kg
Basis: actual ingested
Remarks:
Doses / Concentrations: 25 mg/kg
Basis: actual ingested
Remarks:
Doses / Concentrations: 50 mg/kg
Basis: actual ingested
Remarks:
Doses / Concentrations: 500 mg/kg
Basis: actual ingested
No. of animals per sex per dose:
20 pregnant wistar rats/dose
Control animals:
other: Two negative controls; one treated with water, other treated with 0.5% carboxymethylcellulose

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

Key result
Dose descriptor:
NOAEL
Effect level:
500 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
other: Systemic Toxicity

Maternal abnormalities

Key result
Abnormalities:
no effects observed

Results (fetuses)

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

Effect levels (fetuses)

Key result
Dose descriptor:
NOAEL
Effect level:
500 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Embryotoxicity

Fetal abnormalities

Key result
Abnormalities:
no effects observed

Overall developmental toxicity

Key result
Developmental effects observed:
no

Any other information on results incl. tables

The incidence of fetal malformations in benzoic acid treated rats did not reach statistical significance.

Applicant's summary and conclusion

Conclusions:
In a peer reviwed developmental study on the effects of benzoic acid on pregnant rats, the incidence of fetal malformations of treated rats did not reach statistical significance.
Executive summary:

In a peer reviwed developmental study on the effects of benzoic acid on pregnant rats, benzoic acid at doses of 5, 25, 50, and 500 mg/Kg was administered by stomach tube to groups of 20 pregnant Wistar rats on Gestation Days 6-15. Two negative control groups were maintained: one was treated with water, the other with 0.5% carboxymethylcellulose. A positive control group received either thalidomide or aspirin. Dams were killed on Day 21.

 

Maternal survival was similar for treated and control groups. The incidence of fetal malformations did not reach statistical significance (Polish Academy of Sciences, 1977).