Reaction mass of 4,4'-isopropylidenediphenol and phenol

Long-term toxicity to aquatic invertebrates

Description of key information

Studies considered to have a Klimisch rating of 1, with analytical confirmation of dose and following appropriate internationally recognised guidance, include a Daphnia magna reproduction study with a NOEC of 3.16 mg/L (Caspers, 1998), a rotifer life-cycle study with a NOEC of 1.8 mg/L (Springborn Smithers, 2006a; also reported in Mihaich et al., 2009), a mysid shrimp life-cycle study with a NOEC of 0.170 mg/L (Lee, 2010), and a Marisa cornuarietis snail reproduction study with a NOEC of 0.025 mg/L (Warbritton et al., 2007a; Forbes et al. 2008). The NOEC of 0.025 mg/L from the 328 day Marisa cornuarietis study based on a reduction in female growth was considered the key parameter for the long-term toxicity to aquatic invertebrates.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Dose descriptor:

NOEC

Remarks:

BPA

Effect concentration:

0.025 mg/L

Fresh water invertebrates

Dose descriptor:

EC10

Remarks:

Phenol

Effect concentration:

0.46 mg/L

Marine water invertebrates

Marine water invertebrates

Dose descriptor:

NOEC

Remarks:

BPA

Effect concentration:

0.17 mg/L

Additional information

No experimental data are available for the target substance reaction mass of phenol and 4,4’-isopropylidenediphenol. The toxicity to fish was assessed by examination of the properties of the constituents and impurities of the multi-constituent substance. A justification for read-across is attached to Iuclid section 13.

 

Studies with Bisphenol A

Both a standard, chronic Daphnia magna reproduction study as well as a study to assess the moulting behavior of Daphnia exposed to Bisphenol A were performed. No statistically significant difference in reproduction was observed in the standard OECD 211 study. The NOEC for reproduction was the highest dose tested of 3.16 ppm. Also, no statistically significant differences in the moulting frequency between the control and the two Bisphenol A concentrations (0.316 ppm and 3.16 ppm) were observed.

 

A study was conducted to determine the chronic toxicity of Bisphenol A to the rotifer Brachionus calyciflorus under static test conditions. The intrinsic rate of increase (reproduction) was used to determine the No-Observed-Effect Concentration (NOEC) and the Lowest-Observed-Effect Concentration (LOEC). Based on mean measured concentrations and the intrinsic rate of increase, the No-Observed-Effect Concentration (NOEC) was determined to be 1.8 mg a.i./L. The Lowest- Observed-Effect Concentration (LOEC) was determined to be 3.6 mg a.i./L.

 

A 28-day chronic mysid (Americamysis bahia) life cycle study was performed to determine the effects of Bisphenol A to mysids under flow-through conditions.Mysids (≤22 hours post-release) were used to initiate the life-cycle test. Nominal Bisphenol A concentrations of 38, 75, 150, 300 and 600 µg a.i./L were selected for the definitive exposure and corresponded to time-weighted measured concentrations of 18, 41, 74, 170 and 370 µg a.i./L, respectively. A dilution water control was also employed.First generation (F₀) survival and reproductive success, as well as measurements of growth, as mean total body length and mean dry body weight, for all surviving adult mysids at test termination were assessed. Based on the time-weighted average concentrations and the most sensitive endpoint analysed (reproduction), the Lowest-Observed-Effect Concentration (LOEC) was determined to be 370 µg a.i./L. The No-Observed-Effect Concentration (NOEC) for Bisphenol A and mysids was determined to be 170 µg a.i./L. Therefore, the Maximum-Acceptable-Toxicant Concentration (MATC) was calculated to be 250 µg a.i./L. Since no concentration tested resulted in ≥ 50% mortality, the 28-day LC50 value was empirically estimated to be > 370 µg a.i./L, the highest time weighted average concentration tested.

 

A study was conducted to evaluate the effects of Bisphenol A on fecundity, hatchability, and growth of Marisa cornuarietis under flow-through conditions at a temperature of 25°C. For the adult fecundity trials, no effects of Bisphenol A were detected at any test concentration. From these results the NOEC for this trait is estimated to be >640 μg BPA/L. For the egg hatchability trial, no significant differences between the control and any Bisphenol A concentration were detected for percent hatch or for time to first- or 50% hatch. Thus, the NOEC for hatchability traits is estimated to be > 640 μg/L. For the juvenile growth trial, significant impairments in female growth were detected at 640 μg/L. Though a statistically significant increase in male (but not female) juvenile growth was observed at 1 μg/L, the contributions of breeding pair and inter-juvenile variability contributed measurably more to the variance in juvenile growth rate than Bisphenol A treatment. Thus a NOEC for juvenile growth rate is estimated to be 25 μg BPA/L based on the observed negative effects on female growth at 640 μg/L. Based on the combined results of the adult fecundity trial, the egg hatchability trial and the juvenile growth trial, a NOEC for Marisa cornuarietis of 25 μg BPA/L is proposed. This value is based on the highest concentration at which no statistically significant impairments in juvenile growth were observed (LOEC=640 μg/L).

 

Studies with Phenol

Long-term effects of phenol on Daphnia magna were investigated in a semi-static test at 19 °C over a period of 16 days according to the Dutch Standard Organisation NEN 6502 (1980).

20 -25 daphnids were placed in 1 L test solution prepared in "Dutch Standard Water" with 100 µl ethanol as vehicle. Two replicates were used per concentration. Concentrations were spaced by a factor of 1.8 (concentrations used are not reported). The concentrations were not analytically verified.

Test parameters were inhibition of length increase and reproduction of the daphnids. The most sensitive parameter was growth. As growth reduction will generally result in a lowered reproductive output, this endpoint is of high relevance.

The 16 d EC10 for growth was regarded as the relevant endpoint and was calculated to be 0.46 mg/L.

 

Conclusion

For BPA, the lowest NOEC in freshwater invertebrates was determined to be 25 µg/L; the lowest NOEC in marine invertebrates was 0.17 mg/L. For Phenol the 16 d EC10 in Daphnia magna was 0.46 mg/L. Due to the physicochemical properties of phenol, this major constituent of the reaction mass is capable of targeting aquatic and terrestrial wildlife through a different exposure route than 4,4’-isopropylidenediphenol. Therefore, to adequately characterize the hazard of the reaction mass toward ecotoxicology endpoints, the toxicity and fate of both major constituents of the reaction mass of phenol and 4,4’-isopropylidenediphenol were considered and two sets of PNECs (one for phenol one for 4,4’-isopropylidenediphenol) were derived and an assessment entity approach was applied.