Registration Dossier

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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Administrative data

Endpoint:
health surveillance data
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This is a summary of in vivo studies compiled by an authoritative body (SCF) which drew conclusions on the impact of human exposures to the test substance.

Data source

Reference
Reference Type:
review article or handbook
Title:
Unnamed
Year:
2002
Report date:
2002

Materials and methods

Study type:
other: risk assessment based on animal studies
Endpoint addressed:
other: various endpoints after oral exposure
Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
other: scientifically valid studies according to reproductive toxicity and genetic toxicity protocols
Principles of method if other than guideline:
Review of studies and risk assessment
GLP compliance:
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

Method

Type of population:
general
Ethical approval:
not applicable
Details on study design:
Review of published and unpublished animal studies with impact on human risk assessment

Results and discussion

Results:
The ADI for benzoic acid and its salts is unchanged at 0-5 mg/kg bw/d, and further in vivo studies (reproductive/developmental toxicity and genotoxicity) are no longer required.

Any other information on results incl. tables

Benzoic acid and its salts are in widespread use as food preservatives in the EU. The Scientific Committee for Food (SCF) was first asked to evaluate the safety of benzoic acid and its salts in 1994. In this opinion (SCF, 1994), the Committee raised questions about developmental toxicity and genotoxicity and asked for further studies in these two areas. In view of these data requests, the Committee set only a temporary ADI, of 0 - 5 mg/kg bw based on an overall NOAEL of 500 mg/kg bw/day from long-term and multigeneration studies. The benzoates had previously been evaluated by the Joint FAO/WHO Expert Committee on Food Additives (JECFA), which established an ADI of 0 - 5 mg/kg bw as a sum of benzoic acid and its salts, expressed as benzoic acid (JECFA, 1974). At a later meeting, JECFA recommended a full review of benzoic acid and its salts, together with the flavouring substances benzyl acetate, benzyl alcohol and benzaldehyde (JECFA 1993), in order to determine whether additional studies were needed. In particular the absence of reproductive and developmental toxicity studies was noted. These substances were grouped because of their common metabolic pathway. After receipt of new information, they were re-evaluated in 1996 and the Group ADI of 0 - 5 mg/kg bw was maintained (JECFA, 1997). JECFA was satisfied that the data were sufficient to demonstrate lack of carcinogenicity and lack of toxicity to development and reproduction. The genotoxicity database was also reviewed at that time.

Conclusions: The updated database is much more extensive than that considered by the Committee in 1994, both for developmental toxicity and for genotoxicity. There appear to be sufficient studies to conclude absence of teratogenic potential, with an overall NOAEL for developmental toxicity of 500 mg/kg bw/day, based on effects on fetal weight. The fact that this overall NOAEL takes into account gavage as well as dietary studies gives further reassurance. It is therefore concluded that a further teratogenicity study on benzoic acid should no longer be required. Similarly for genotoxicity, while some of the in vitro tests have been positive or equivocal, all the results from in vivo studies have been negative. It is therefore concluded that an in vivo study for clastogenic activity on benzoic acid should no longer be required. On the basis of these data and the other types of study previously evaluated by the Committee, the Committee can establish a full Group ADI of 0 - 5 mg/kg bw for benzoic acid and its salts including benzyl alcohol and related benzyl derivatives used as flavourings.

Applicant's summary and conclusion

Conclusions:
The human ADI for benzoic acid and its salts is unchanged at 0-5 mg/kg bw/d, and newly-commissioned in vivo studies (reproductive/developmental toxicity and genotoxicity) are no longer required to be undertaken. This study is informative for evaluation of the toxicity of members of the Alkyl Benzoates category.