Download Comparison of Toxicity for Methyl Iodide and Methyl Bromide

Comparison of Toxicity for Methyl Iodide and Methyl Bromide
Prepared by Susan E. Kegley, Ph.D., Consulting Scientist, Pesticide Action Network
Methyl iodide (iodomethane) is currently being introduced in some parts of the U.S. as a replacement for
methyl iodide. There are some inaccuracies being circulated about the relative toxicity of methyl iodide vs
methyl bromide. This document summarizes the known toxicity information for methyl bromide and
methyl iodide and cites the sources of the data.
Quick Summary:
• Methyl iodide is about four times more neurotoxic than methyl bromide. This means that the
amount of methyl iodide required to cause noticeable neurotoxicity in experimental animals is
four times lower than the amount of methyl bromide required for the same effect.
•
Methyl iodide is 1.1-3.5 times more acutely toxic than methyl bromide. This means that the
amount of methyl iodide needed to cause death in 50% of exposed animals is 1.1 to 3.5 times less
than the amount of methyl bromide, for the same effect. The variation is related to the species
tested—rats or mice—and the length of time the animals were exposed.
•
The OSHA-allowed exposure level for methyl iodide is four times lower than that for
methyl bromide. The Occupational Safety and Health Administration (OSHA) sets Permissable
Exposure Limits (PELs) for different chemicals, and has set the PEL for methyl iodide four times
lower than that for methyl bromide.
•
Methyl iodide is a carcinogen; methyl bromide is not. Methyl iodide is on the California
Proposition 65 list of carcinogens, and methyl bromide is not. Methyl iodide causes thyroid
tumors.
•
Methyl iodide causes developmental toxicity at doses four times lower than methyl bromide.
Methyl iodide causes “fetal losses” (miscarriages) by interfering with the thyroid hormone levels
during pregnancy. Methyl bromide causes birth defects and is on the California Prop 65 list of
developmental toxicants, but these effects are observed at doses higher than those for methyl
iodide toxicity. Methyl iodide has not yet been reviewed for inclusion on the Prop 65 list for
developmental toxicity.
•
Methyl iodide is toxic to the thyroid gland. Because of the iodine in methyl iodide, this
chemical targets the thyroid gland. The developmental toxicity is related to methyl iodide’s
interference with thyroid hormone levels that are essential for successful fetal development.
Methyl bromide does not have the same type of effect on the fetus, although it does have other
effects.
•
For short-term and long-term exposures, methyl bromide is up to twice as toxic as methyl
iodide. The endpoints here are salivary gland metaplasia (a change in cell type that is an adaptive
response to a stressor like chemical exposure) for methyl iodide and lesions of the lining of the
nose for methyl bromide.
Tables 1 and 2 on the following pages provide more detailed information and the sources of the
information.
Table 1: Comparison of Acute Toxicity for Methyl Iodide and Methyl Bromide
Study Description
Inhalation Acute
Neurotoxicity – Rats
Six-hour exposure
(EPA guideline 870.6200)
Methyl iodide
Methyl bromide
Ratio, MeBr/MeIk
NOAEL = 27 ppm
LOAEL = 93 ppm
NOAEL = 100 ppm
LOAEL = 350 ppm
NOAEL, 3.70
LOAEL, 3.76
Acute Inhalation – Rat
4-hour LC50 exposure
(EPA guideline 870.1300)
691 ppm*
776 ppm
1.12
LC50 Mouse inhalation
1-hour exposure
865 ppmc
1,200 ppmd
1.39
LC50 Rat inhalatione
4-hour exposure
225 ppm
780 ppm g
3.47
OSHA PELh
8-hour time-weighted avg.
5 ppm
20 ppm
4.00
LC50 Rat inhalationi
30 minute exposure
1,750 ppm
2,800 ppm
1.60
LD50 Rat orale
76 mg/kg (0.53
mmol/kg)
214 mg/kg (2.25
mmol/kg)
2.82 (on a per gram
basis)
4.24 (on a per
molecule basis)
LC50 = concentration that is lethal to 50% of the test animals; NOAEL = No Observed Adverse Effect Level, the dose at which
no adverse effects were observed; LOAEL = Lowest Observed Adverse Effect Level, the lowest dose at which adverse effects
were still observed; ppm = parts per million; mg/kg = milligrams of pesticide per kilogram of body weight; mmol/kg =
millimoles of pesticide per kilogram of body weight.
* There appears to be a mistake in the data table of Appendix B of the Iodomethane Preliminary Risk Assessment, U.S. EPA,
January 2006, so it is not clear what the 4-h LC50 should be for iodomethane. At another place in the risk assessment, the value is
given as 4 mg/L (691 ppm).
a
Iodomethane Preliminary Risk Assessment, Appendix B: Toxicity Profile, U.S. EPA, January 2006.
b
Methyl Bromide Preliminary Risk Assessment, Appendix A: Toxicity Profile, U.S. EPA, July 2005.
c
G.D.Clayton, F.E. Clayton, (eds.) Patty’s Industrial Hygiene and Toxicology, Volumes 2A-2F, Toxicology. 4th ed., John Wiley
& Sons (New York, 1993-1994.
d
Alexeef GV et al; J Toxicol Environ Health 15 (1): 109-23 (1985).
e
R.J. Lewis, Sax’s Dangerous Properties of Industrial Materials, 9th ed, Vol. 1-3, Van Nostrand-Reinhold (New York, 1996).
f
Kato W et al; Indust Health 24 (2): 87-103 (1986).
g
IPCS, Intox Databank, Canadian Center for Occupational Safety and Health, http://www.intox.org/databank/index.htm.
h
OSHA Permissable Exposure Limits, 29 CFR 1910.1000, Table Z-1: Limits for Air Contaminants, 2003.
i
G.N. Bakhishev, Relation between the chemical structure and toxicity of some halolgenated aliphatic hydrocarbons, Fiziol. Akt.
Veshchestva 7:35-36 (1975) (Rs), from NIOSH Current Intelligence Bulletin 43: Monohalomethanes, Methyl Chloride, Methyl
Bromide and Methyl Iodide, Sept. 1984, http://222.cdc.gov/niosh/84117_43.html.
j
Because lower LD50 values, NOAELs and LOAELs mean HIGHER toxicity, this ratio gives the factor by which methyl iodide is
more toxic than methyl bromide.
k
This column shows the ratio of the doses required to cause an effect between methyl bromide and methyl iodide. A lower dose
means the compound is more toxic, with less exposure required to see an effect.
Table 2: Comparison of Other Types of Toxicity for Methyl Iodide and Methyl Bromide
Methyl iodide
Methyl bromide
Comparison
MeBr/MeIb
NOAEL = 10 ppm
LOAEL = 20 ppm
NOAEL = 40 ppm
LOAEL = 80 ppm
NOAEL, 4.0
LOAEL, 4.0
State of CA (Prop 65): Not
yet evaluated as a
developmental toxicant.
State of CA (Prop 65):
Listed as a developmental
toxicant.
Thyroid toxicitya
Thyroid toxicity is the
primary mechanism of
developmental toxicity and
carcinogenicity.
No thyroid toxicity
MeI is a thyroid
toxicant; MeBr
is not.
Short-term non-cancer
toxicity via the inhalation
a
route
NOAEL = 5 ppm
LOAEL = 20 ppm
NOAEL = 5 ppm
LOAEL = 10 ppm
NOAEL, 1.0
LOAEL, 0.5
Long-term, non-cancer
toxicity via the inhalation
a
route
NOAEL = 5 ppm
LOAEL = 20 ppm
NOAEL = not identified, but
< 3 ppm
LOAEL = 3 ppm
NOAEL < 0.6
LOAEL, 0.15
EPA: Not likely to be
carcinogenic to humans at
doses that do not disrupt
thyroid hormone
homeostasis. Likely to be
carcinogenic at doses that
do disrupt thyroid hormone
homeostasis.
EPA: Not likely to be a
human carcinogen.
MeI is listed as
a carcinogen by
the state of
California;
MeBr is not.
Study Description
Developmental toxicity
Carcinogenicity
a
a
State of CA (Prop 65):
Listed as a carcinogen.
International Agency for
Research on Cancer:
Inadequate evidence for
carcinogenicity to humans
and limited evidence for
carcinogenicity to animals;
the overall evaluation of
carcinogenicity to humans
was "not classifiable" (group
3).
State of CA (Prop 65):
Evaluated for
carcinogenicity, but not listed
as a carcinogen.
International Agency for
Research on Cancer:
Inadequate evidence for
carcinogenicity to humans
and limited evidence for
carcinogenicity to animals;
the overall evaluation of
carcinogenicity to humans
was "not classifiable" (group
3).
NOAEL = No Observed Adverse Effect Level, the dose at which no adverse effects were observed; LOAEL = Lowest Observed
Adverse Effect Level, the lowest dose at which adverse effects were still observed; ppm = parts per million.
Data taken from EPA’s risk assessments for methyl iodide (Iodomethane: Revised HED Human Health Risk Assessment Which
Incorporates Results of Human Iodine Monitoring, 10/1/2007,
http://www.regulations.gov/fdmspublic/component/main?main=DocketDetail&d=EPA-HQ-OPP-2005-0252, Document number
EPA-HQ-OPP-2005-0252-0051) and methyl bromide (Methyl Bromide: Phase 5 Health Effects Division (HED) Human Health
Risk Assessment For Soil, Greenhouse, and Residential/Structural Uses, April 10, 2007,
http://www.regulations.gov/fdmspublic/component/main?main=DocketDetail&d=EPA-HQ-OPP-2005-0123, Document number
EPA-HQ-OPP-2005-0123-0285.
a
b
This column shows the ratio of the doses required to cause an effect between methyl bromide and methyl iodide. A lower dose
means the compound is more toxic, with less exposure required to see an effect.