Toxicological Evaluation and Limit Values for Nonylphenol, Nonylphenol Ethoxylates, Tricresyl, Phosphates and Benzoic Acid 3. Human toxicity3. Human toxicity Sodium benzoate is rapidly hydrolysed to benzoic acid in the body and there seems no reason to believe that sodium benzoate differs toxicologically from benzoic acid. Therefore, in the following some data based on investigations of sodium benzoate are included where relevant to describe the toxicological profile of benzoic acid. Conversion factor: 100 mg sodium benzoate is equivalent to 84.7 mg benzoic acid. 3.1 Short term toxicity Inhalation No data have been found. Oral intake A number of very early studies have shown gastro-intestinal disturbances (dyspepsia, nausea and vomiting) after single oral administration of 1-5 g sodium benzoate/benzoic acid to humans, corresponding to approx. 14-70 mg /kg bw expressed as benzoic acid. (Meissner & Shepard 1866 - quoted from JECFA 1983 and Goodman & Gilman 1966). A more recent study has confirmed these early stated values: Nausea, bloating, and epigastric discomfort have been observed in humans after oral administration of 4 g sodium benzoate corresponding to doses from 39-71 mg/kg bw (expressed as benzoic acid) (Jackson et al. 1987). Humans given 25 mg/kg bw for 20 days suffered from irritation (probably gastro-intestinal), discomfort, weakness and malaise (Wiley & Bigelow 1908 - quoted from SCF 1994). The effects were described as reversible and maybe caused by a disturbance of acid-base balance rather than local tissue damage. Some individuals are hypersensitive to benzoic acid. In such sensitive persons oral doses corresponding to 10-250 mg benzoic acid (less than 4 mg/kg bw) have been shown to induce eczema (Vieluf et al. 1990 and BIBRA 1989 - quoted from IUCLID 1996). Anaphylaxis was induced in a young female after ingestion of a meal containing sodium benzoate as preservative. A subsequent provocation test with oral administration of 160 mg sodium benzoate (corresponding to 2.5 mg benzoic acid/kg bw) induced localised urticaria (Michils 1991). It is known that persons who suffer from asthma, rhinitis, or urticaria may undergo exacerbation of symptoms following ingestion of foods or beverages containing benzoic acid or benzoates (JECFA 1983). A trained worker suffered from allergic reactions of increasing intensity while being constantly exposed to benzoic acid during work (no exposure levels are given). After oral exposure to 425 mg sodium benzoate (approx. 5 mg benzoic acid/kg bw) he developed anaphylaxis and showed milder reactions later when eating food containing benzoic acid (Pevny 1981). Dermal contact Benzoic acid may cause non-immunologic immediate contact reactions (erythema, local urticaria) within 30-45 min. of skin application. A number of skin tests with different doses in various vehicles have been carried out. (Forsbeck & Skog 1977, Rademaker & Forsyte 1989, Lewis et al. 1989, Ylipieti & Lahti 1989, Kligman 1990 and Larmi et al.,1989 - quoted from IUCLID 1996). 3.2 Long term toxicity Inhalation Benzoic acids in tailor chalk has been connected with occurence of rhinitis, shortness of breath and "burning eyes" of students and teachers from a fashion school. They were exposed to sublimated Benzoic acid as well as benzoic acid dust (Aberer 1992). The authors mentioned that after notification of the formula of this special chalk they could ascribe the problems to benzoic acid since only this chemical had been added for special purposes to the normal chalk. Duration and level of exposure was not mentioned. The exposure was intermittent and the symptoms disappeared when the persons were not longer exposed. Oral intake Very early studies have shown that doses up to 14 mg benzoic acid/kg bw/day for 88-92 days were without visible effect (Gerlach 1909- quoted from SCF 1994) and dietary administration of 0,3-0,4 g benzoic acid (4,3-5,7 mg/kg bw/day) for 62 days had no effect on blood picture, urine composition, nitrogen balance and well being (Chittenden et al. Quoted from JECFA 1983). Dermal contact Three workers of a pharmaceutical plant exposed to airborne sodium benzoate developed transient non-immunological contact urticaria related to skin contamination with sodium benzoate. No information on the concentration of the sodium benzoate in the air was given (Nethercott 1991). Eye irritation "Burning eyes" has been connected with exposure to benzoic acid in tailors chalk (Aberer 1992, see above). 3.3 Reproductive / developmental effects No data have been found. 3.4 Genotoxic effects No data have been found. 3.5 Carcinogenic effects No data have been found.
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