Toxicological Evaluation and Limit Values for Nonylphenol, Nonylphenol Ethoxylates, Tricresyl, Phosphates and Benzoic Acid

7. Evaluation

Studies have shown that benzoic acid may induce adverse effects in humans as well as animals. However, most of the studies are of an earlier date and do not meet the requirement of today’s quality guidelines. Only a few studies reflect the effect of benzoic acid after inhalation.

The sparse human data have shown that exposure to airborne benzoic acid may lead to reversible irritation of the respiratory system and eyes or skin reactions. However, none of these studies provide any exposure levels upon which a NOAEL/LOAEL can be set.

A four-week well performed inhalation study in rats indicate that even at the lowest level tested (25 mg benzoic acid/m³) histopathological changes were observed. The treatment related effects were confined to the respiratory system and most likely of local nature.

Oral studies in animals have shown that the acute toxicity of benzoic acid is rather low (LD₅₀: 1700-2500 mg/kg bw). However, in humans sensitive to benzoic acid an acute systemic effect (anaphylaxis) has been observed after ingestion of a meal containing sodium benzoate as a preservative. Gastro-intestinal disorders in humans have been reported after single oral or short term administration of 1-5 g, corresponding to approx. 14-70 mg /kg bw. Doses below 14 mg/kg bw/day for 88-92 days were without visible effect.

Most of the oral animal studies are inadequate and do not - or at best only very sparsely - include information about gross pathology and histopathology. Further, the mean benzoic acid consumption has been calculated according to different methods implying that the NOAEL/ LOAEL values are subject to a rather high degree of uncertainty. It is not possible to draw attention to one particular study for establishing a NOAEL. However, most of the data points toward the same effect: a systemic toxic effect which clinically appears as disorders of the nervous system or death at high dose levels and lesions to the liver and kidneys at lower levels. Administration of sodium benzoate or benzoic acid to mice and rats at levels below 1 % in the diet (approx. 600 mg/kg bw) seems without toxic effect. Levels above this may result in severe systemic disorders.

The reprotoxicity studies are insufficient to draw any conclusions from, but exposure to levels of benzoic acid not leading to maternal toxicity probably do not cause developmental/foetal toxicity.

Benzoic acid is not mutagenic and not genotoxic in vivo. The two carcinogenicity studies available do not meet the requirements of today’s guidelines and are inadequate for evaluation.

Based upon the available data from human as well as animal studies, the critical effects after inhalation of benzoic acid is considered to be an irritative, most likely reversible effect on the respiratory system and eyes and skin reactions. For estimating a limit value in air, the LOAEL at 25 mg benzoic acid/m³ from the rat study is considered most relevant.

Although the critical effect of benzoic acid is considered to be irritation to various tissue surfaces, it cannot be excluded that inhaled benzoic acid may cause an acute systemic effect (anaphylaxis) in humans sensitive to benzoic acid.