Toxicity Issues

What is the difference between LD50s and toxicity values used in human health risk assessment?

The default toxicity values in RISC are from EPA's Integrated Risk Information System (IRIS) database (http://www.epa.gov/iris/index.html), which is the gold standard here in the US. There are detailed summaries in the IRIS database describing all of the animal studies used to extrapolate a human health toxicity value. There is also some information about the process in general in an “Introduction” section on the above web page. Having all EPA’s risk/toxicity assessments for each chemical available on the web is a fairly recent development (4-6 years ago?) so the German regulators may not be familiar with it yet. (That was just a “save face” comment.)

What happened to 1,2-DCE?

The toxicity values for 1,2-DCE (cis) were withdrawn from IRIS many years ago. I believe this is because EPA felt that the animal studies were flawed or insufficient to develop toxicity values. EPA characterizes it as Class D with respect to carcinogenicity, meaning that there has been no evidence in human, animal or mutagenicity studies that the chemical causes cancer. The non-carcinogenic toxicity values (RfDs) that are currently in RISC are based on the old values that EPA had published before they determined that the underlying studies were insufficient. This is standard practice here in the US when doing a risk assessment for cis 1,2-DCE.

The LD50's are not used to develop human toxicity values because they are based on (very crude) acute (short term) exposures. Generally, LD50's are developed in order to estimate an initial dose for a chronic (long-term) exposure for the rats (or whatever). Many chemicals are more toxic when the exposure is at lower doses but for a longer time. So the LD50's do not translate well when trying to estimate human health risk.

LD50's also do not indicate whether or not the chemical is a carcinogen which usually has a big effect on the estimated toxicity value. For example, table salt has a fairly low LD50, however in small doses it appears to be completely non-toxic. On the other hand, I believe you could ingest a fairly high dose of benzene, for example, (so it may have a high LD50 based on a single dose) but when small amounts of benzene are ingested over a lifetime it has been shown to cause cancer in humans.

This is one of the comments from the toxicologist at Chevron:

The risk assessment that has been performed is actually more conservative than one that would be done on the basis of LD50 values. The US EPA toxicity values are based on chronic exposure experiments in which animals were repeatedly exposed to the chemicals of concern over a lifetime. In reality, the acceptable dose levels for this type of chronic exposure are much lower than LD50 values, leading to a more conservative and health protective risk analysis.

On this question:

> They also referred to another document on water solubility of TCE and DCE,

> EPA MNA protocol 600/R-98/128 that were lower than what we found in

> reality at this German site. Is this a question for a toxicologist too or

> rather for Vic?

Is it possible that a small amount of free product could be in the samples? Also, it seems to me that it could be possible that the solubility is different because of the other chemicals present. However, I would have expected the solubility to decrease, not increase, because of Raoult's Law for mixtures.

Solubility values reported in the literature vary quite a bit for some chemicals. I used the EPA's Soil Screening Guidance (SSG) for the default solubility values in RISC. This is a fairly recent, "peer-reviewed" source and many of the States here are using the chemical values from this document as defaults in their RBCA programs. (I’m not sure it is the best source however.)

Chemical Properties

Solubility

Here is a summary of the solubility values from Howard and Meylan and the SSG:

	Howard and Meylan (mg/l)	EPA SSG (mg/l)
TCE	1.10E3	1.10E3
1,1-DCE	1.25E3	2.25E3
trans, 1,2-DCE	6.30E3	6.30E3
cis 1,2-DCE	2.80E4	3.50E3
Vinyl chloride	8.80E3	2.76E3

I didn’t realize the large variation between the solubility values reported for cis 1,2-DCE. EPA’s values came from their Superfund Chemical Data Matrix (SCDM) which is available on-line but I’ve found it’s a little difficult to use. You might find their references there.

Kow

Octanol water partioning coefficient.

Chemical Property References

One of the best references I've found for chemical properties is Howard and Meylan's "Handbook of Physical Properties of Organic Chemicals":

Howard, P.H., and W.M. Meylan. 1997. Handbook of Physical Properties of Organic Chemicals, CRC Press, Boca Raton, FL.

U.S. Environmental Protection Agency. May 1996. Soil Screening Guidance: Technical Background Document, Office of Solid Waste and Emergency Response, EPA/540/R-95/128.

U.S. EPA Integrated Risk Information System (IRIS): http://www.epa.gov/iris

Risk Assessment References

Howard, P.H., and W.M. Meylan. 1997. Handbook of Physical Properties of Organic Chemicals, CRC Press, Boca Raton, FL.

U.S. Environmental Protection Agency. May 1996. Soil Screening Guidance: Technical Background Document, Office of Solid Waste and Emergency Response, EPA/540/R-95/128.

U.S. EPA Integrated Risk Information System (IRIS): http://www.epa.gov/iris