4,4’- Isopropylidenediphenol – inhalable fraction. Documentation of proposed values of occupational exposure limits (OELs)
Authors: Gromiec Jan 
Published: December 2018

4,4’- Isopropylidenediphenol (bisphenol A) is a white solid present in the form of crystals or flakes. It is used mostly in the production of epoxy resins (appr. 95% of its consumption). It is also used in the polycarbonate plastics, unsaturated polyester, polysulphonte and polyacrylate resins as well as flame retardants. Polycarbonate plastics are used to make products such as emulsions for thermal printers employed for printing tickets, labels, receipts, faxes etc.
The routes of occupational exposure during production and application of bisphenol A are the respiratory system and the skin.
The exact number of occupationally exposed to 4,4’- isopropylidenediphenol is not known but taking into account the wide use of polycarbonate and polyester resins it can be counted in thousands. Because of only trace amounts of bisphenol A in most of the resins, the levels of exposure are usually minimal.
In Poland 4,4’- isopropylidenediphenol is used mainly as a component of glues for electronic parts, PVC stabilizer, addition components of epoxy resins and brake fluids. In 2010 only 4 persons were reported as occupationally exposed to bisphenol A dust in concentrations exceeding Polish OEL (5 mg/ m3) – 2 in the crop and animal production, hunting and related service activities sector and 2 in the water transport sector. In 2013 no workers exposed above OEL value were reported.
Oral LD50 values beyond 2 000 mg/kg bw were found in the rat and mouse, and dermal LD50 values above 2 000 mg/kg are evident in the rabbit.
4,4’- Isopropylidenediphenol has been classified as Repr. 1.B, H360F (may damage fertility or the fetus) and substance that causes serious eye damage (H318) and may cause respiratory system irritation (H355).
In workers having occupational contact with 4,4’- isopropylidenediphenol irritation of eyes, skin and respiratory system was observed. In animal experiments it was clearly shown that bisphenol A did not cause skin irritation, however, it was shown that the compound is an eye irritant. Slight and transient nasal tract epithelial damage was observed in rats exposed to bisphenol A dust which suggests that it appears to have a limited respiratory irritation potential.
There are several reports of patients with dermatitis responding to BPA in patch tests, however, it is unclear whether bisphenol A or related epoxy resins were the underlying cause of the hypersensitive state. No reliable sensitisation animal data from experiments meeting the required standards are available.
Toxicity of bisphenol A has been tested on mice, rats and dogs. The compound administered orally caused mainly a decrease in body weight gain; minor changes in organ weight, mostly in liver; respiratory disorders, diarrhea and death. From chronic experiments the liver and kidney seem to be the target organs.
There are no in vivo data on mutagenic activity of bisphenol A. It also does not appear to produce either gene mutations or structural chromosome aberrations in bacteria, fungi or mammalian cells in vitro. The compound did not induce gene mutations in yeasts; sister chromatid exchange tests carried out on mammalian cells also gave negative effects.
No information on human cancerogenicity of 4,4’- isopropylidenediphenol has been found in the literature and databases available. In a 103-week test on rats and mice of both sexes no convincing evidence indicating carcinogenic action of bisphenol A was found.
Some studies indicate negative action of 4,4’- isopropylidenediphenol on reproduction which is a result of a mechanism of its action – in in vivo test the compound was found to bind to the nuclear estrogen receptors. However, data on the embryotoxic activity of bisphenol A and its effects on reproduction are not conclusive. Contradictory findings between the studies have been reported in several studies in rodents which was thoroughly discussed in the EFSA Report of 2015. In studies carried out in accordance with the FDA/NTCR standards 4,4’- isopropylidenediphenol effects on reproduction have been seen only at high doses showing also other toxic effects. Comprehensive tests with a wide range of doses did not confirm effects of 4,4’- isopropylidenediphenol on reproduction and development at low doses below 5 mg/kg bw. In Chinese epidemiological studies, impaired sperm quality in workers occupationally exposed to bisphenol A has been found, however, the effect of other concurrent exposures cannot be excluded.
4,4’- Isopropylidenediphenol in all species studied is conjugated with glucuronic acid and excreted as glucuronid with urine. The major route of excretion is via faeces; regardless of the route of entry 50-80% of the administered dose is eliminated with faeces in the unchanged form. In humans the compound is excreted as glucuronide or sulphate conjugates in urine.
In Poland as well as in most other countries 5 mg/m3 as OEL and 10 mg/m3 as STEL have been established for 4,4’- isopropylidenediphenol.
Scientific Committee on Occupational Exposure Limits (SCOEL) has proposed to establish an Indicative Occupational Exposure Limit (IOEL) in workplace air at the level of 2 mg/m3 taking the inhalation NOAEC of 10 mg/m3 from the rat study as a starting point for recommending an OEL. The critical effect in this study was respiratory tract irritation. According to SCOEL there is no toxicological basis for recommending an additional specific short-term exposure limit (STEL). Assignment of “skin” notation was also not recommended.
The proposed OEL value for 4,4’- isopropylidenediphenol (inhalable fraction) has been derived from its irritating action on nasal tract epithelium in an inhalation study on experimental animals. The proposed OEL value is 2 mg/m3. This value should also protect workers against toxic effects on liver and kidney.
There are no grounds for establishing a short-term exposure limit (STEL) nor for recommending a biological limit value (BLV).
It is also proposed to introduce the following assignments: “I” – irritating substance and “A” – sensitizing substance.