EU CLP is changing to include new criteria for classification, including:
- Endocrine disruption for human health
- Endocrine disruption for the environment
- vPvB
- vPvM
- PBT
- PMT
These are described on the page ‘New CLP Hazard Classes for Endocrine Disruptors and Persistent Chemicals’, but understanding what the data actually means is important.
In summary, none of these are good, and although persistence in its own right may not imply hazard, the concerns over ‘forever chemicals’ mean these are a target for greater control. If persistence is coupled with known hazards (toxicity), or causes biological changes to the endocrine system or is accumulative, then the concerns are amplified.
In all cases, if these criteria are met, then it is likely that the substance is on its way to the Candidate List for further control through Authorisation or Restriction as Substances of Very High Concern (SVHC).
But what do these mean?
Endocrine Disruptors
The term ‘endocrine disruptor’ is a broad description of chemicals that mimic, inhibit or otherwise interfere with hormones (endocrine system) found in plants and animals, including humans. Most commonly, the concern is linked to reproductive toxicity including fertility and birth defects, but have a broader impact and can be linked to neurodevelopmental disorders, cancer, diabetes, obesity etc.
Many substances already classified as toxic for reproduction, carcinogens or even STOT may owe their toxicity to ‘endocrine’ effects. However, unless there is detailed high level toxicity work, often involving the use of many animals, it is difficult to confirm the link between disruption to the endocrine system and the observed toxic effects.
Due to the difficulty in confirming endocrine impact, there is still debate among toxicologists whether certain substances are true endocrine disruptors or not and classification will need to reflect the degree of confidence.
The primary focus is on EATS (Oestrogenic, Androgenic, Thyroidal and Steroidogenic) types of disruption, as these are the most well studied, and many of these effects can be picked up in well-performed modern reproduction toxicity tests. However, many older studies did not look at the necessary endpoints and there is an even lower level of certainty.
New test methods are still being argued over, not least due to the concerns over the use of large numbers of animals and potential costs and the OECD is working to develop a range of (relatively) low cost in-vitro methods.
Examples are:
- Performance-based Test Guideline for Human Recombinant Estrogen Receptor (hrER) In Vitro Assays to Detect Chemicals with ER Binding Affinity (OECD 493)
- Performance-Based Test Guideline for Stably Transfected Transactivation In Vitro Assays to Detect Oestrogen Receptor Agonists and Antagonists (ER STTA) (OECD 455)
- Stably Transfected Human Androgen Receptor Transcriptional Activation Assay for Detection of Androgenic Agonist and Antagonist Activity of Chemicals (AR STTA) (OECD 458)
- H295R Steroidogenesis Assay (OECD 456)
- Androgen Receptor Binding Assay (US EPA OPPTS 890.1150)
- Aromatase Assay (US EPA OPPTS 890.1200)
There is a concern though that like the use of in-vitro methods for sensitisation (allergenic) effects, the in-vitro chemistry-based tests are overly sensitive and we may end up with many innocent chemicals being branded as endocrine disruptors.
What is certainly of greater concern is when the potential for endocrine disruption (T for Toxic) combines with potential for persistence and movement in the environment.
PBT, vPvB, PMT and vPvM substances
PBT = Persistent, Bioaccumulative and Toxic
vPvB = very Persistent, very Bioaccumulative
PMT = Persistent, Mobile and Toxic
vPvM = very Persistent, very Mobile
These are mainly of concern due to the fact that they are P (persistent) as they fail to break down and are therefore difficult to remove from the environment. In the case of B (Bioaccumulative) substances, there is a risk of a build up (biomagnification) in animals, including humans and of course, if T (Toxic) then any accumulation is likely to result in eventual adverse effects.
Substances causing endocrine disruption are of course T.
The other concern is that these substances can be transported; this is not just local transport into a water supply, but globally and even if not designated (yet) as T, we don’t always know what the long-term effects are. Politically, these have been dubbed as ‘Forever Chemicals’ and can be difficult and expensive to clean up and not always removed even by advanced filtration and treatment processes.
Chemicals considered P, B or M are likely to be restricted for consumer use as it is generally accepted that consumers will ignore instructions on safe disposal and simply dispose down the sink (and into treatment works where removal is unlikely).
Test criteria
Although REACH ‘base-set’ testing will give indications on potential as SVHC, complex higher-level tests may be needed to confirm the final assessment.
The likelihood of meeting the criteria of concern for the environment is summarised below:
Key:
N/R = Not Relevant
N = No
U = Unlikely
L = Likely
Y = Yes
| Test (Base level testing) | Persistent | Bioaccumulative | Mobile | |||
| P | vP | B | vB | M | vM | |
| Water solubility > 100 mg/l | N/R | N/R | U | N | Y | L |
| Adsorption coefficient Log Koc > 3 | N/R | N/R | U | U | Y | L |
| Adsorption coefficient Log Koc > 2 | N/R | N/R | U | N | Y | Y |
| Partition Coefficient Log Kow < 4.5 | N/R | N/R | U | N | U | N |
| Partition Coefficient Log Kow > 4.5 | N/R | N/R | Y* | L | N | N |
| Biodegradation screening > 60% 28 days | N | N | N/R | N/R | N/R | N/R |
| Inherent biodegradation > 60% 60 days | U | N | N/R | N/R | N/R | N/R |
| Inherent biodegradation < 60% 60 days** | Y* | Y* | N/R | N/R | N/R | N/R |
* Higher level testing may be needed such as fish bioaccumulation or special water and sediment degradation tests to prevent being considered P or B or vPvB
The criteria for T includes environmental toxicity as well as classification criteria for mammalian toxicity such as mutagenic, carcinogenic, toxic for reproduction or endocrine disruption for human health or the environment.
- Aquatic Chronic 1 (NOEC < 0.01 mg/l)
- Carc 1A or 1B
- Muta 1A, 1B
- Repr 1A, 1B or 2
- Other evidence of systemic or chronic toxicity, such as STOT RE 1 or 2
- Endocrine disruptor for human health or the environment
For full criteria on PBT and vPvB, see the ECHA guidance: