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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
repeated dose toxicity: oral
Remarks:
combined repeated dose and reproduction / developmental screening
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
1960
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study predates current guidelines. This older study meets generally accepted scientific standards. The data is published in German and has been accepted as valid by panels of toxicologists including those at JECFA, EFS and WHO.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Die vertraglichkeit der benzoesaure im chronischen futterungsversuch
Author:
Kieckebusch W and Lang K
Year:
1960
Bibliographic source:
Arzneimittel-Forschung 10: 1001-1003.
Reference Type:
review article or handbook
Title:
Benzoic Acid and Sodium Benzoate
Author:
World Health Organization
Year:
2000
Bibliographic source:
International Chemical Assessment Document 26: 1-48. http://www.inchem.org/documents/cicads/cicads/cicad26.pdf
Reference Type:
publication
Title:
Unnamed
Year:
1983
Reference Type:
review article or handbook
Title:
Safety assessment of alkyl benzoates as used in cosmetics
Author:
Becker LC, Bergfeld WF, Belsito DV, et al.
Year:
2012
Bibliographic source:
Int. J. Toxicol. 31:342S-72S
Reference Type:
review article or handbook
Title:
SIDS Initial Assessment Report for the 13th SIAM: Benzoates
Author:
OECD HPV Programme
Year:
2001
Bibliographic source:
http://www.inchem.org/documents/sids/sids/BENZOATES.pdf
Report date:
2001
Reference Type:
review article or handbook
Title:
Unnamed
Year:
2002
Report date:
2002

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
other: OECD Guideline: 416
Principles of method if other than guideline:
This is a 4-generation repeated dose toxicity study of benzoic acid.
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Reference substance name:
Benzoic acid
EC Number:
200-618-2
EC Name:
Benzoic acid
Cas Number:
65-85-0
IUPAC Name:
benzoic acid
Details on test material:
no data available

Test animals

Species:
rat
Strain:
other: Bayer-Elberfeid
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Details on oral exposure:
In a 4-generation study, 20 rats/sex/group were dosed continuously with 0.5 and 1% in the diet, equivalent to 250 or 500 mg/kg/day, of benzoic acid.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Generations 1 and 2: lifelong
Generation 3: 16 weeks
Generation 4: until breeding
Frequency of treatment:
Daily (continuous) in the diet
Doses / concentrations
Remarks:
Doses / Concentrations:
0.5 and 1% in the diet (estimated as 250-500 mg/kg bw/d, 275- 500 mg/kg bw/d, or 375-750 mg/kg bw/day by different expert groups)
Basis:
nominal in diet
No. of animals per sex per dose:
20 per sex per group.
Control animals:
yes, plain diet
Details on study design:
Chronic repeated dose toxicity study, in which animals were allowed to mate through 4 generations. The animals of the 3rd generation were killed and examined histopathologically after 16 weeks (after lactation of the pups).
Positive control:
No data

Examinations

Observations and examinations performed and frequency:
Animals were examined for weight, weight gain and food efficiency (measured by protein efficiency)) and organ weights.
Sacrifice and pathology:
HISTOPATHOLOGY:Yes
The animals of the 3rd generation were killed and examined histopathologically after 16 weeks (after lactation of the pups).

Results and discussion

Results of examinations

Clinical signs:
not specified
Mortality:
not specified
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
No adverse effects were observed in 4 generations of rats at doses of 1% benzoic acid in the feed. There was slightly increased survival at the dose of 0.5%. No signficant findings were noted in the post-mortem examination. The NOAEL is 1% (approximately equivalent to 500-750 mg/kg bw/d).

Effect levels

Dose descriptor:
NOAEL
Effect level:
500 - 750 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: as 1% in the diet

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Rats were administered 0, 0.5 and 1% benzoic acid in the diet for 4 generations. No harmful effects were observed on growth, fertility, development, lactation and lifespan. The no effect dietary level was 1%, approximately equivalent to 500-750 mg/kg bw/d. This study is informative for evaluation of the toxicity and environmental fate of members of the Alkyl Benzoates category, and is adequate for filling the data requirement for the registration of this substance. It is valid for hazard classification and risk assessment.