Neurotoxicity: the EPA 2,4-D pesticide study giving the safe level for neurotoxicity – straight from Dow laboratories.

2013-02-02 053

The US EPA uses the same Dow Chemical Company study that the WHO uses to declare a safe level for 2,4-D neurotoxicity exposure to humans.

Whether under it’s registration eligibility decision (that gives the levels safe for the USA population to consume and is reviewed every 12 years or so) or the major carcinogenicity study that is often cited when any debate on whether 2,4-D can cause cancer to humans.  It is only one Dow study that counts.

In the USA you will find that it is only Dow studies that are included in these major government neurotoxicity reviews of 2,4-D.

This is shameful.

 

The are 2 places to look for 2,4-D neurotoxicity information held with the EPA:

1. USA EPA Reregistration Eligibility Decision (RED) for 2,4-D under the section III ‘A. Human Health Risk Assessment’.

2.  EPA Carcinogenicity Peer Review for 2,4-D dated July 17, 1996.   This is the major carcinogenicity review cited whenever the topic of ‘has 2,4-D been really well reviewed for cancer’ is raised.

 

1. USA EPA Reregistration Eligibility Decision (RED) for 2,4-D under the section III ‘A. Human Health Risk Assessment’.

Toxicological endpoints:  Acute and long term:  Acute neurotoxicity study. This level is relevant to infants, adults and is also the level for ‘children post application exposure to turf’ .  This is the study that provides the 67 mg/kg oral acute neurotoxicity study in rats (which should be 75 mg/kg – see WHO extract below):

MRID 43115201  Mattsson, J.; McGuirk, R.; Yano, B. (1994a) 2,4-Dichlorophenoxyacetic Acid (2,4-D): Acute Neurotoxicity Study in Fischer 344 Rats: Lab Project Number: K-002372-066. Unpublished study prepared by The Dow Chemical Co. 451 p.

Groups of 10 male and 10 female Fischer 344 rats received 2,4-D in corn oil by gavage as single doses of 0, 15, 75 or 250 mg/kg bw.

There is another study quoted in the ‘Data Supporting Guideline Requirements’ in Appendix B:  Neurotoxicity Screening Battery:

MRID 43293901  Mattsson, J.; Jeffries, T.; Yano, B. (1994b) 2,4-Dichlorophenoxyacetic Acid: Chronic Neurotoxicity Study in Fischer 344 Rats: Lab Project Number: K- 002372-064N: K-002372-064. Unpublished study prepared by The Dow Chemical Co. 1091 p.

Unfortunately in the EPA EPA Reregistration Eligibility Decision document you can’t actually see the studies.  Mattson 1994a and 1994b are on pages 72-73 of the WHO 1996 Review of 2,4-D.   (Cross ref using lab project number)  http://www.24d.org/govtrev/WHO-1996-FAO%20Review.pdf

What is confusing is that EPA gives 67 mg/kg bw/day and WHO gives 75 mg/kg bw/day for the same study.  There is a mixup regarding the Mattson 1994a study.

The neurotoxicity summary on page 19 said this:

On April 8, 2003, based on the weight of evidence presented, the Agency reaffirmed the previous conclusion that a developmental neurotoxicity (DNT) study in rats is required for 2,4-D because there is a concern for developmental neurotoxicity resulting from exposure to 2,4-D. There is evidence of neurotoxicity, including clinical signs such as ataxia and decreased motor activity in pregnant rabbits following dosing during gestation days 6-15 in studies on 2,4-D itself and 2,4-D amine salts and esters, and tremors in dogs that died on test following repeat exposure to 2,4-D. Incoordination and slight gait abnormalities (forepaw flexing or knuckling) were also observed following dosing in the acute neurotoxicity study with 2,4-D.

Looking at Appendix B, ‘Requirement 870.6300   Section 83-6 : Developmental Neurotoxicity’  EPA states there is a ‘datagap’.

 

Listed in the bibliography, you will find other neurotoxicity studies listed that are not paid for by Dow or 2,4-D Task Force – however the critical studies that give the NOAEL – the toxicological endpoints – the data that counts – are always Dow.

2.  EPA Carcinogenicity Peer Review for 2,4-D dated July 17, 1996.

Mattson JL., Jeffries TK., and Yano BL. 2,4-D: neurotoxicity study in Fischer 344 Rats – Final. The Toxicology Research Laboratory, Dow Chemical Co. Study ID K-002372-064N. 6/28/94.  MRID 43293901. HED Document 011614

Harvard Study

Acute toxicity: Harvard Study quotes WHO (Dow and Industry Task Force) and Mattson (Dow) studies:

  1. Mattson. JL., Albee RR., Johnson KA., and Quast JF., Neurotoxicologic examination of rats dermally exposed to 2,4-D amine for three weeks. Neurobehav. Toxicol. Taratol. 8:255-263 (1986).  Dow Chemical Co. Michigan.
  2. Mattson JL., Johnson KA and Albee RR. Lack of neuropathalogic consequences of repeated dermal exposure to 2,4-dichlorophenoxyacetic acid in rats. Fundam. Appl. Toxicol. 6: 175-181 (1986). Dow Chemical Co. Michigan. http://www.sciencedirect.com/science/article/pii/0272059086902745

 

 

 

Extract:  World Health Organisation p.72

Only one study is held in the ‘Toxicological Critieria estimating guidance values for dietary and non-dietary exposure to 2,4-D’ (P.85)

Short term (1-7 days): Oral single dose neurotoxicity rat, acid 75mg/kg bw

Mattsson, J.L., McGuirk, R.J. & Yano, B.L. (1994a) 2,4-D acute neurotoxicity study in Fischer 344 rats. Unpublished report No. K-002372-066 from The Dow Chemical Company, Midland, MI, USA. Submitted to WHO by Industry Task Force II on 2,4-D Research Data, Indianapolis, Indiana, USA.

Single doses of 0,15,75,250 mg/kg bw/day resulted in increased incidences of incoordination on day one at level 250 mg/kg bw/day such as slight gait abnormalities (forepaw flexing and knuckling). The incidence has decreased to control levels by day 4 in males and day 3 in females.  NOAEL for neurotoxicity 75 mg/kg bw/day.

 

 

 

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