TR 063 – Reproductive and General Toxicology of some Inorganic Borates and Risk Assessment for Human Beings
TR 063 : Reproductive and General Toxicology of some Inorganic Borates and Risk Assessment for Human Beings | February 1995
A review of the toxicology of some inorganic borates is provided together with a risk assessment for man. The toxicology database is largest for boric acid (H3BO3) and borax (Na2B4O7.10H2O). Limited data are available for sodium perborate (mono and tetrahydrate) and boric oxide and even less is available (acute data only) for borax pentahydrate and anhydrous borax.
The toxicological end-points of concern identified for both boric acid and borax from animal studies were fertility and developmental toxicity. Generally, these effects were observed in more than one species. Data were available on fertility from dog and rat studies on both borax and boric acid. In addition, mouse data were available on boric acid.
For both boric acid and borax, the lowest NOAEL for fertility in male and females rats was determined to be 17 mg boron/kg bw. Effects seen at the LOAEL included testicular toxicity, reduced spermiation in males and decreased ovulation in females. At higher dose levels testicular atrophy was observed. A lower NOAEL was available from a dog study (8.8 mg boron/kg bw) but the data were considered unsuitable for risk assessment purposes. For female mice, the NOAEL for fertility was around 27 mg boron/kg bw. Effects included reduced ovulation and decreased pup weights in the second generation offspring.
For developmental toxicity, only data on boric acid were available from rat, mouse and rabbit studies. The rat was confirmed as the most sensitive species with a NOAEL of 9.6 mg boron/kg bw, based on reduced foetal body weight and skeletal effects observed at the LOAEL.
Taking NOAELs for fertility and developmental toxicity, an uncertainty factor (UF) was applied to derive a tolerable daily intake for a 60 kg human. Justification for an uncertainty factor of 30 is presented, taking into account the nature of the hazard, adequacy of the database and detailed knowledge of how borates are absorbed, distributed and excreted without liver metabolism. Limited human data were also available for consideration. A tolerable daily intake of borates for a 60 kg person was calculated to be 34 mg boron/day and 19.2 mg boron/d which could be ingested without the risk of fertility (testicular) or developmental effects respectively.
Based on the tolerable daily intake of 19.2 mg boron and taking into consideration the maximum boron intake from diet is 7 mg/d from food, mineral waters and other beverages including wine, up to 12 mg boron could be obtained from other sources including drinking water without exceeding the total daily intake. With a drinking water standard at the current EC Guide Level of 1 mg boron/l, the total boron intake from food and water is well below the calculated total daily intake. Therefore, the current drinking water Guide Level of 1 mg boron/l is considered to be sufficiently conservative and there is no need for it to be reduced even further to 0.3 mg boron/l as recently recommended by WHO (1993).
The overall conclusion is that, at high doses, boric acid and borax cause adverse effects on fertility and developmental toxicity in animals models. Preliminary investigations have been carried out to try to identify the mechanism concerning the testicular effects observed, but very little relevant work has yet been done to establish the cause of developmental toxicity effects. The precise mechanism of action is unclear but it is known that borates are not metabolised, neither do they accumulate in the body except for low deposits in bone. At borate concentrations found in the environment either as a food constituent or when present in fresh waters and in some drinking waters, the risk assessment has demonstrated that exposure is not likely to cause any undue health risk to human beings.