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Toxicological Profile for White Phosphorus. Atlanta (GA): Agency for Toxic Substances and Disease Registry (US); 1997 Sep.
Toxicological Profile for White Phosphorus.
Show detailsThe Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) [42 U.S.C. 9601 et seq.], as amended by the Superfund Amendments and Reauthorization Act (SARA) [Pub. L. 994991, requires that the Agency for Toxic Substances and Disease Registry (ATSDR) develop jointly with the U.S. Environmental Protection Agency (EPA), in order of priority, a list of hazardous substances most commonly found at facilities on the CERCLA National Priorities List (NPL); prepare toxicological profiles for each substance included on the priority list of hazardous substances; and assure the initiation of a research program to fill identified data needs associated with the substances.
The toxicological profiles include an examination, summary, and interpretation of available toxicological information and epidemiologic evaluations of a hazardous substance. During the development of toxicological profiles, Minimal Risk Levels (MRLs) are derived when reliable and sufficient data exist to identify the target organ(s) of effect or the most sensitive health effect(s) for a specific duration for a given route of exposure. An MRL is an estimate of the daily human exposure to a hazardous substance that is likely to be without appreciable risk of adverse noncancer health effects over a specified duration of exposure. MRLs are based on noncancer health effects only and are not based on a consideration of cancer effects. These substance-specific estimates, which are intended to serve as screening levels, are used by ATSDR health assessors to identify contaminants and potential health effects that may be of concern at hazardous waste sites. It is important to note that MRLs are not intended to define clean-up or action levels.
MRLs are derived for hazardous substances using the no-observed-adverse-effect level/uncertainty factor approach. They are below levels that might cause adverse health effects in the people most sensitive to such chemical-induced effects. MRLs are derived for acute (1-14 days), intermediate (15-364 days), and chronic (365 days and longer) durations and for the oral and inhalation routes of exposure. Currently, MRLs for the dermal route of exposure are not derived because ATSDR has not yet identified-a method suitable for this route of exposure. MRLs are generally based on the most sensitive chemical-induced end point considered to be of relevance to humans. Serious health effects (such as irreparable damage to the liver or kidneys, or birth defects) are not used as a basis for establishing MRLs. Exposure to a level above the MRL does not mean that adverse health effects will occur.
MRLs are intended only to serve as a screening tool to help public health professionals decide where to look more closely. They may also be viewed as a mechanism to identify those hazardous waste sites that are not expected to cause adverse health effects. Most MRLs contain a degree of uncertainty because of the lack of precise toxicological information on the people who might be most sensitive (e.g., infants, elderly, nutritionally or immunologically compromised) to the effects of hazardous substances. ATSDR uses a conservative (i.e., protective) approach to address this uncertainty consistent with the public health principle of prevention. Although human data are preferred, MRLs often must be based on animal studies because relevant human studies are lacking. In the absence of evidence to the contrary, ATSDR assumes that humans are more sensitive to the effects of hazardous substance than animals and that certain persons may be particularly sensitive. Thus, the resulting MRL may be as much as a hundredfold below levels that have been shown to be nontoxic in laboratory animals.
Proposed MRLs undergo a rigorous review process: Health Effects/MRL Workgroup reviews within the Division of Toxicology, expert panel peer reviews, and agencywide MRL Workgroup reviews, with participation from other federal agencies and comments from the public. They are subject to change as new information becomes available concomitant with updating the toxicological profiles. Thus, MRLs in the most recent toxicological profiles supersede previously published levels. For additional information regarding MRLs, please contact the Division of Toxicology, Agency for Toxic Substances and Disease Registry, 1600 Clifton Road, Mailstop E-29, Atlanta, Georgia 30333.
White Phosphorus Smoke Acute Inhalation
MINIMAL RISK LEVEL WORKSHEETS
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| Chemical Name: White Phosphorus Smoke |
| CAS Number: 7723-14-0 |
| Date: September 5, 1996 |
| Profile Status Draft 3 |
| Route: [X] Inhalation [ ] Oral |
| Duration: [X] Acute [ ] Intermediate [ ] Chronic |
| Graph Key: 9 |
| Species: Human |
Minimal Risk Level: 0.02 [ ] mg/kg/day [X] mg/m3
Reference: White and Armstrong 1935
Exuerimental design:(human study details or strain, number of animals per exposure/control groups, sex, dose administration details): Four men were exposed by inhalation to an average concentration of 0.187 mg/L white phosphorus for 5 minutes in a gassing chamber. No controls were used.
Effects noted in study and corresponding doses: Throat irritation, coughing and headache were reported at 187 mg/m3 (LOAEL). One of the subjects reported pain in the eyes and lungs. Calculations: 187 mg/m3 X 5/60 minx l/24 hr X 1/3OUF = 0.02 mg/m3.
Dose and endpoint used for MRL derivation: A dose of 187mg/m3 was used for respiratory effects in humans.
[ ] NOAEL [x] LOAEL
Uncertainty Factors used in MRL derivation:
- [Xl 3 for use of a minimal LOAEL
- [ ] 3 for extrapolation from animals to humans
- [x] 10 for human variability
Was a conversion used from ppm in food or water to a mg/body weight dose?
If so, explain: No
If an inhalation study in animals, list the conversion factors used in determining human eouivalent dose:
Other additional studies or pertinent information which lend support to this MRL: Although a 5-minute exposure duration is usually too brief to consider for MRLs and expanding over a 24-hour period would result in an exposure level of 0.6 mg/m3, further experiments indicated that exposure for longer durations would result in more severe effects. In the field, white phosphorus smoke was generated at 0.1 mg/m3 to protect soldiers from detection. In addition the OSHA PEL is 0.1 mg/m3. Therefore, expanding the 5minute duration over 24 hours is reasonable.
Agency Contact (Chemical Manager): Patricia Richter
Agency Review Date: 1° review:_____
2° review:_____
White Phosphorus Intermediate Oral
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| Chemical Name: White Phosphorus |
| CAS Number: 7723-14-0 |
| Date: September 5, 1996 |
| Profile Status Draft 3 |
| Route: [ ] Inhalation [X] Oral |
| Duration: [ ] Acute [X] Intermediate [ ] Chronic |
| Graph Key: 42 |
| Species: Rat |
Minimal Risk Level: 2 x 10-4 [x] mg/kg/day [ ] mg/m3
Reference: International Research and Development Corporation (IRDC) 1985
Experimental design: (Human study details or strain, number of animals per exposure/control groups, sex, dose administration details): A one generation reproduction study was conducted in rats. Elemental phosphorus was administered orally by gavage to Charles River COBS CD rats at dosage levels of 0.005,0.015 and 0.075 mg/kg/day, at a dose volume of 5 ml/kg. For each dosage group including control, 15 male and 30 female rats were used. Administration of the test and control materials (corn oil) to both sexes began 80 days prior to mating. The F0 generation was mated twice to produce “a” and “b” offspring. In males, dosing continued until sacrifice. Administration to the females continued through gestation and weaning of the pups. Individual dosages were based on the most recent weekly body weights.
Effects noted in studv and corresponding doses: Elemental phosphorus administered orally by gavage at a dosage level of 0.075 mg/kg/day adversely affected parturition, decreased the mean number of viable pups at birth and increased the mean number of stillborn pups. Similar fmdings were not observed at dosage levels of 0.015 mg/kg/day (NOAEL) or less. Calculations: 0.015 mg/kg/day X l/l00UF = 2 X l0-4 mg/kg/day.
Dose and endpoint used for MRL derivation: A NOAEL of 0.0 15 mg/kg/day was used for the MRL derivation.
[X] NOAEL [ ] LOAEL
Uncertainty Factors used in MRL derivation:
- [] 3foruseofa minimal LOAEL
- [X] 10 for extrapolation from animals to humans
- [X] 10 for human variability
Was a conversion used from ppm in food or water to a mg/body weight dose?
If so, explain: No
If an inhalation study in animals, list the conversion factors used in determining human equivalent dose:
Other additional studies or pertinent information which lend support to this MRL: At first examination, it appeared that no intermediate oral MRL could be derived because the lowest dose indicated on Table 2-2 was 0.075 mg/kg/day, which was associated with increased mortality in pregnant rats in two reproductive studies, one by Bio/dynamics (1991) and one by IRDC (1985). However, in the IRDC study (1985), 0.075 mg/kg/day was a NOAEL for systemic endpoints (#31 in LSE Table 2-2), such that the lower doses in the study did not appear in the LSE table. No effects were seen in rats at lower doses of 0.005 and 0.015 mg/kg/day. Therefore, the 0.015 mg/kg/day dose, which was not associated with increased mortality and produced no other effects, was the NOAEL for the intermediate database. In the Bio/dynamics (1991) study, only the 0.075 mg/kg/day dose was used, and in addition to increased mortality, was associated with hepatic toxicity (#30 in LSE Table 2-2). Therefore, the critical endpoint is hepatic. It was noted that the EPA derived an RfD from the same NOAEL of 0.015 mg/kg/day in the same study (IRDC 1985).
Agency Contact (Chemical Manager): Patricia Richter
Agency Review Date: 1° review:
2° review:
- ATSDR MINIMAL RISK LEVEL - Toxicological Profile for White PhosphorusATSDR MINIMAL RISK LEVEL - Toxicological Profile for White Phosphorus
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