FDA Acknowledged Ortho-Phthalates Could Be Grouped Into Classes For Safety, Then Punted

Maricel Maffini, consultant and Tom Neltner, Chemicals Policy Director

In May, FDA decided to allow continued use of nine ortho-phthalates in food packaging and processing equipment but punted on deciding whether or not using those phthalates is safe. We’ve written about the petitions that resulted in the decision, along with the agency’s decision to “abandon” the use of 19 other phthalates (here, here, here, and here). We’ve also written about how phthalates that industry and FDA say are no longer on the market are showing up in our food (here and here). Today, however, we focus on whether those nine phthalates are a class of related substances—and the implications for public health if they are.

FDA’s obligation to evaluate related chemicals as a class

FDA’s regulations state that additives “that cause similar or related pharmacological effects will be regarded as a class, and in the absence of evidence to the contrary, as having additive toxic effects.” In denying our petition, FDA acknowledged that some phthalates could be in a class of related substances. For example, FDA described studies showing that seven phthalates reduced testosterone production – an effect called antiandrogenicity – during fetal development. This caused malformation of the male reproductive system (primarily malformed genitals in male infants). The agency balked at declaring all phthalates anti-androgenic because four of them did not show that effect.[1]

But rather than move forward with a safety assessment of the use of the antiandrogenic phthalates as a class of chemicals with similar toxicity, FDA dropped the issue, implicitly sending the message the chemicals are safe. This is contrary to the agency’s obligation. When making a final decision on a food additive petition that allows the use of a substance, FDA must explicitly decide the use is safe after considering the cumulative effect of it and related substances in the diet.[2]

In contrast to FDA’s failure to act, the Consumer Product Safety Commission, responding to safety concerns, took action five years earlier and banned use of antiandrogenic phthalates in children’s products.

A phthalate scorecard: Where we stand on which phthalates can be used and their health effects

The table below provides a scorecard for the nine phthalates that remain in use. Of those substances, studies showed that seven were associated with developmental effects, including four which have antiandrogenic effects. Two phthalates were never studied for developmental effects.

ATSDR sets safe level for DEHP to protect against developmental effects

In its 2022 toxicological profile of DEHP, perhaps the most studied phthalate for its developmental toxicity, the Agency of Toxic Substances and Disease Registry (ATSDR) estimated the minimal risk level (MRL)[3] to be 0.1 micrograms of DEHP per kilogram of body weight per day (µg/kg bw/d).

We estimated the exposure to DEHP from the National Health And Nutrition Examination Survey (NHANES) biomonitoring program to be 0.13 and 0.20 µg/kg bw/d for the 90^th and 95^th percentile of the total population. In both cases, the values were above the ATSDR MRL—meaning estimated exposure is already higher than the level considered to be of “no appreciable risk” to health.

The FDA regulation regarding classes also states that where two or more chemicals in the same class are present in the diet, the tolerance or exposure limit for the combined chemicals in the class be the same as for the chemical with the lowest tolerance unless there are alternative quantitative methods available that show a higher tolerance is safe. In this context, we identified seven other phthalates with developmental toxicity[4], in addition to DEHP, whose exposure could be estimated from the NHANES biomonitoring. Adding the mean exposure for all eight, we calculated a combined exposure of 1.47 µg/kg bw/d – or more than 14 times the ATSDR safe level for DEHP alone. While food was not the only source of , eliminating all food uses is an important step in reducing the public’s exposure to phthalates to protect children from harm.

Conclusions

FDA is not adequately protecting the health of children by leaving the issue unresolved six years after agreeing to consider the safety of phthalates. It should have performed a safety assessment of phthalates it continues to allow in food.

[1] FDA, NRDC, et al.; Denial of Food Additive Petition, 87 Federal Register 31066, May 20, 2022. See page 31,070 for discussion. FDA said “One of the most commonly studied pharmacological effects for phthalates is antiandrogenicity; antiandrogens affect the endocrine system by modulating the production of testicular testosterone pertaining to the development of the male reproductive system. The data cited in the petitioners’ literature search indicates that, among the 12 phthalates with available toxicological information, 7 phthalates exhibit antiandrogenic effects ( i.e., butyl benzyl phthalate (BBP), diisobutyl phthalate (DiBP), DBP, dicyclohexyl phthalate (DCHP), dihexyl phthalate (DHP), DEHP, and diisononyl phthalate (DINP)) (see Supp., August 24, 2017, Appendix B). Four other phthalates (i.e., dimethyl phthalate [DMP], diethyl phthalate [DEP], di-n-octyl phthalate [DnOP], and DiDP) did not have that effect.

[2] See 21 U.S.C. § 348(b).

[3] ATSDR defines minimal risk level as “an estimate of the daily human exposure to a hazardous substance that is likely to be without appreciable risk of adverse non-cancer health effects over a specified duration of exposure”.

[4] DEHP, DCHP, DIDP, DINP, and DEP from the table above as well as Di-n-butyl phthalate (DBP), Butylbenzyl phthalate (BBP), and Di-isobutyl phthalate (DiBP). We included the latter because they are developmental toxicants with antiandrogenic effects.