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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
three-generation reproductive toxicity
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1960
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Justification for type of information:
The study was evaluated to be suitable for this endpoind by ECHA/RAC (2012)

Data source

Reference
Reference Type:
other: Background document for RAC oppinion on benzoic acid
Title:
Background document to the Opinion proposing harmonised classification and labelling at EU level of Benzoic acid, CHL report
Author:
Committee for Risk Assessment, RAC
Year:
2012
Bibliographic source:
Background document to the Opinion proposing harmonised classification and labelling at EU level of Benzoic acid, CHL report, Committee for Risk Assessment, RAC, November 2012, ECHA/RAC/CLH-O-0000001687-65-02/A1
Report date:
2012

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The study was evaluated to be suitable for this enpoind by ECHA/RAC
GLP compliance:
no
Remarks:
Study was performed before 1. of June 2008

Test material

Constituent 1
Chemical structure
Reference substance name:
Benzoic acid
EC Number:
200-618-2
EC Name:
Benzoic acid
Cas Number:
65-85-0
Molecular formula:
C7H6O2
IUPAC Name:
benzoic acid
Test material form:
not specified

Test animals

Species:
rat
Strain:
not specified
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Details on exposure:
0, 0.5 and 1% benzoic acid added to the diet, corresponding to approximate doses of 0, 250 and 500 mg/kg bw/d
Duration of treatment / exposure:
lifetime
Frequency of treatment:
daily
Doses / concentrationsopen allclose all
Dose / conc.:
0 ppm (nominal)
Dose / conc.:
5 000 ppm (nominal)
Remarks:
approximately 250 mg/kg/day
Dose / conc.:
10 000 ppm (nominal)
Remarks:
approximately 500 mg/kg/day
No. of animals per sex per dose:
20

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed

Effect levels (P0)

Key result
Dose descriptor:
NOAEL
Effect level:
500 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
mortality
body weight and weight gain
organ weights and organ / body weight ratios
histopathology: non-neoplastic

Target system / organ toxicity (P0)

Key result
Critical effects observed:
no

Results: P1 (second parental generation)

General toxicity (P1)

Clinical signs:
no effects observed
Dermal irritation (if dermal study):
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed

Results: F1 generation

General toxicity (F1)

Clinical signs:
no effects observed
Mortality / viability:
no mortality observed
Body weight and weight changes:
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Histopathological findings:
no effects observed

Details on results (F1)

No effect on offspring survival and bw development, testes weight

Effect levels (F1)

Key result
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
500 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
mortality
body weight and weight gain
organ weights and organ / body weight ratios
histopathology: non-neoplastic

Target system / organ toxicity (F1)

Key result
Critical effects observed:
no

Overall reproductive toxicity

Key result
Reproductive effects observed:
no
Lowest effective dose / conc.:
500 mg/kg bw/day (nominal)
Treatment related:
no

Applicant's summary and conclusion

Conclusions:
For benzoic acid reproductive toxicity was assessed in a non-guideline 3-generation study performed in rats with 0, 0.5 and 1% benzoic acid added to the diet, corresponding to approximate doses of 0, 250 and 500 mg/kg bw/d. These doses failed to produce detectable toxic effects on parental and offspring generations or reproductive capacity (ECHA/RAC 2012).
Executive summary:

For benzoic acid reproductive toxicity was assessed in a non-guideline 3-generation study performed in rats with 0, 0.5 and 1% benzoic acid added to the diet, corresponding to approximate doses of 0, 250 and 500 mg/kg bw/d. These doses failed to produce detectable toxic effects on parental and offspring generations or reproductive capacity (ECHA/RAC 2012).