National Academies of Science
Quotes from Study
Toxicological Risks of
Selected Flame-Retardant Chemicals
Commission on Life Sciences (CLS)
Finally, potential exposures to FRs applied to
furnishing fabrics within the home have not been studied. Thus, there is
little basis for estimates of exposure to such materials. There are few, if
any, measurements of exposures under relevant conditions of exposure, and
the subcommittee located no quantitative measurements of such exposures.
Subsequent iterations of the procedure would then depend
on finding more defensible information about the exposure conditions. The
subcommittee was unable to find any such information and recommends
collection of such information—a process that should be relatively
straightforward but is outside the subcommittee’s charge.
Jenkins, R.O., P.J.Craig, W.Goessler, and K.J.Irgolic.
1998. Antimony leaching from cot mattresses and sudden infant death syndrome
(SIDS). Hum. Exp. Toxicol. 17(3):138–139.
FRs are to be used to prevent or reduce a known risk—that of fires
caused by ignition of FR-treated upholstered furniture. Even if FRs were to
produce adverse effects, the net effect of using them might nevertheless be
a reduction in risks. Determination of the acceptability of the various
risks requires consideration of the trade-offs involved. The subcommittee’s
charge did not include evaluation of trade-offs, and it did not attempt to
make such evaluation.
From page 32
fractional rate (per unit time) of zinc borate extraction by saliva is
estimated as 0. 001/d, based on leaching of antimony from polyvinyl chloride
cot mattresses (Jenkins et al. 1998).
[This seems to be a poor comparison. Antimony
leaching from vinyl like on a notebook or other household items is a
nonporous surface. This is far different than a powder like boric acid
applied to textile fibers.]
The area density of the FR (the application
rate to the fabric or back-coating—mass per unit surface area). This
value is chemical specific and was chosen at the highest value
likely to be used. It ranged from 2 to 7.5 mg/cm2
depending on the treatment type. (The range was chosen from the
experience of the UK’s textile market in meeting the UK’s
The area of body in contact with the couch was
chosen to be 2,200 cm2. This value is based on 8,880 cm2
for the total body surface of the upper extremities (trunk, arms,
and neck) of an adult (EPA Exposure Factors Handbook,
Table 4–4). A worst-case estimate of body surface repeatedly in
contact with furniture for long periods would be about 1/4 of the
bare upper torso, or 2,200 cm2.
A worst-case estimate of body surface repeatedly in
contact with furniture for long periods would be about 1/4 of the bare upper
torso, or 2,200 cm2.
The fractional rate (per unit time) of FR
extraction by water (e.g., sweat) assumed to be present under the
given conditions. This rate is chemical specific; it was generally
estimated from extraction measurements or laundering tests and
ranged from 0.0004 to 0.038 per day.
The fraction (dimensionless) of time spent on
the couch by the adult was assumed to be 1/4, or 6 hr/d (every day).
The subcommittee believes, based on measurements of how people spend
their time, that 6 hr/d may be considered a reasonable upper bound.
The adult body weight (mass) was assumed to be
1982). However, blood boron concentrations were increased within 2–6
hr after application of the same amount of boric acid in a
water-based jelly, indicating that the vehicle in which boric
acid is applied to the skin affects absorption.
As discussed in the
section on Absorption, boron has been detected in the urine after
exposure to boric acid via the dermal, inhalation, and oral
In the occupational
setting, toxic effects following exposure to boron are generally
acute, and include nosebleed, nasal irritation, sore throat, cough,
and shortness of breath (IPCS 1998).
toxicity appears to be the most sensitive endpoint for boric acid.
There is a large body of literature indicating developmental and
reproductive effects within the same order of magnitude, therefore,
the confidence in the overall database is high. Therefore, the
subcommittee has high confidence in the oral RfD for boric acid
The fractional release rate of antimory trioxide is estimated as 0.
001/d, based on the leaching of antimony from polyvinyl chloride cot
mattresses (Jenkins et al. 1998).
1998. Antimony leaching from cot mattresses and sudden infant
death syndrome (SIDS). Hum.
rate (per unit time) of zinc borate extraction by saliva is
estimated as 0. 001/d, based on leaching of antimony from
polyvinyl chloride cot mattresses (Jenkins et al.
leaching from cot mattresses and sudden infant death
syndrome (SIDS). Hum.
Zinc borate is typically composed of 45% ZnO and 34%
boric anhydride (B2O3), with 20% water of hydration.
Zinc borate is used as a flame retardant
boric acid is readily absorbed following inhalation and
oral exposure. Kent and McCance (1941, as cited in Moore 1997) page 153
In humans, boron has
been measured in the brain and liver following boric acid poisonings (see
review, Moseman 1994).
As discussed in the
section on Absorption, boron has been detected in the urine after exposure
to boric acid via the dermal, inhalation, and oral routes. Following
ingestion of boric acid by six male volunteers, greater than 90% of an
ingested dose was excreted in the urine within 96 hr (Jansen et al. 1984).
Dermatitis has been
reported following occupational exposure to borax
In the occupational
setting, toxic effects following exposure to boron are generally acute, and
include nosebleed, nasal irritation, sore throat, cough, and shortness of
breath (IPCS 1998).
A study (Tarasenko et al. 1972), summarized by Moore
(1997), found a decrease in sexual
activity in 28 workers exposed to very high concentrations of boron (10
mg/m3). Examination of the semen from six of the workers
demonstrated a reduction in semen volume, a decrease in the number of
spermatozoa, and decreased sperm motility
The free ion of boric
acid, boron, is an essential nutrient for plants, and there is some evidence
supporting essentiality in animals, including humans (see reviews, Woods
1994; Nielsen 1996). The essentiality of boron in humans is under
consideration by the Institute of Medicine; however, no dietary intakes are
Information on the acute toxicity of boron compounds, including boric acid,
in humans comes from severe poisonings, often related to old medical
treatments or accidental exposures. Following ingestion of large amounts of
boric acid, gastrointestinal symptoms occur first (nausea, vomiting, and
diarrhea), followed by erythema, exfoliation, and desquamation of the skin
No consistent lethal dose of boric acid has been
reported in adults, but lethal doses in infants and children of
2–3 g and 5–6 g,
respectively, have been reported (Moore 1997). Death occurred following
ingestion of a large amount of boric acid (2.5% solution), which was
accidently used instead of water to prepare an infant’s formula (Wong et al.
1964, as cited in Moore 1997).
Krasovskii et al. (1976) dosed white random-bred rats
(number of animals not given) with boric acid (0, 0.015, 0.05, and 0.3 mg
boron/kg body weight) for 6 mo. Statistically significant decreases in
mobility time, acid resistance, and osmotic resistance were seen at 0.3 mg
boron/kg body weight. Mobility time and acid resistance were also decreased
at 0.05 mg boron/kg body weight. The authors identified a NOAEL of 0.015 mg
boron/kg and a LOAEL of 0.05 mg boron/kg.
At 262.5 mg boron/kg-d, both compounds decreased
testis/brain weight ratios. Complete
atrophy of the testis occurred in one male
at 2.6 mg boron/kg-d, in four males
Developmental and reproductive end points are the most
sensitive effects for boron compounds following oral exposure. The lowest
NOAEL identified was 8.8 mg boron/kg-d in the dog study by Weir and Fisher
(1972). However, in the report by Moore (1997), questions were raised about
that study due to a high level of abnormalities in the control group. The
number of animals was also quite small in that study. Therefore, the study
by Price et al. (1996a), which provided the next lowest values, with a LOAEL
of 13.3 mg boron/kg-d and a NOAEL of 9.6 mg boron/kg-d, based on
developmental effects, is the critical study for the reproductive and
developmental effects of boron.
appears to be the most sensitive endpoint for boric acid. Price et al.
(1996a) identified the lowest LOAEL and the highest NOAEL
In order to derive an
oral RfD for zinc borate from the RfDs for zinc compounds and boric acid,
the relative contributions of zinc and boron to zinc borate were determined.
Boron comprises approximately 11.3% (w/w) of zinc
The main effects of boron are reproductive and
EXPOSURE ASSESSMENT AND RISK CHARACTERIZATION
The assessment of
noncancer risk by the dermal route of exposure is based on the scenario
Chapter 3. This exposure scenario assumes that an adult spends 1/4th of
his or her time sitting on furniture upholstery treated with zinc borate,
that 1/4th of the upper torso is in contact with the upholstery, and that
clothing presents no barrier. Zinc borate is considered to be ionic, and is
essentially not absorbed through the skin. However, to be conservative, the
subcommittee assumed that ionized zinc borate permeates the skin at the same
rate as water, with a permeability rate of 10−3 cm/hr (EPA 1992).
Using that permeability rate, the highest expected application rate for zinc
borate (2 mg/cm2), and Equation 1 in
Chapter 3, the subcommittee calculated a dermal exposure level of 6.3×10−3
mg/kg-d. The oral RfD for zinc borate (0.6 mg/kg-d; see Oral RfD in
Quantitative Toxicity section) was used as the best estimate of the internal
dose for dermal exposure. Dividing the exposure level by the oral RfD yields
a hazard index of 1.0×10−2. Thus it was concluded that zinc
borate used as a flame retardant in upholstery fabric is not likely to pose
a noncancer risk by the dermal route.
The assessment of the
noncancer risk by the inhalation route of exposure is based on the scenario
Chapter 3. This scenario corresponds to a person spending 1/4th of his
or her life in a room with low air-change rate (0.25/hr) and with a
relatively large amount of fabric upholstery treated with zinc borate (30 m2
in a 30-m3 room), with this treatment gradually being worn away
over 25% of its surface to 50% of its initial quantity over the 15-yr
lifetime of the fabric. A small fraction, 1%, of the worn-off zinc borate is
released into the indoor air as inhalable particles and may be breathed by
the occupant. Equations 4 through 6 in
Chapter 3 were used to estimate the average concentration of zinc borate
present in the air. The highest expected application rate for zinc borate is
about 2 mg/cm2. The estimated release rate for zinc borate is
2.3×10−7/d. Using those values, the
estimated time-averaged exposure concentration for zinc borate is 0.19 µg/m3.
Although lack of sufficient data precludes deriving an
inhalation RfC for zinc borate, the oral RfD (0.6 mg zinc borate/kg-d; see
Oral RfD in Quantitative Toxicity section), which represents a conservative
estimate, was used to estimate an RfC of 2.1 mg/m3 (see
Chapter 4 for the rationale).
Division of the exposure concentration (0.19 µg/m3)
by the estimated RfC (2.1 mg/m3) results in a hazard index of
9.1×10−5. Therefore, the subcommittee concluded that, under the
worst-case exposure scenario, exposure to zinc borate particles from its use
as an upholstery fabric flame retardant is not likely to pose a noncancer
Systemic toxicity and
death occurred in rabbits following dermal application of 8g/kg antimony
trioxide (Myers et al. 1978), and application of an unspecified dose of
antimony trioxide in a paste of “artificial acidic or alkalinic sweat”
(Fleming 1938). Both studies indicate that antimony trioxide is absorbed
dermally in rabbits.
Elevated blood and
urine antimony levels were reported in workers occupationally exposed to
antimony, suggesting that antimony trioxide is absorbed following inhalation
exposure (Cooper et al. 1968; Lüdersdorf et al. 1987; Kim et al. 1997).
Dermatitis was reported
in workers occupationally exposed to 0.4–70.7 mg antimony/m3 (Renes
1953; McCallum 1963; Potkonjak and Pavlovich 1983; White et al. 1993).
Death occurred in one
out of four rabbits following a single dermal exposure to 8 g/kg antimony
trioxide (Myers et al. 1978), and in one out of four rabbits exposed to 2
g/kg antimony trioxide (Ebbens 1972). Systemic toxicity and death occurred
in three out of eight rabbits, but not in rats, following short-term
exposure (20–21 d) to an unspecified dose of antimony trioxide (Fleming
1938). Gross pathologies were seen in the liver, lung, stomach, and kidney.
In humans, the lungs
are the primary targets following inhalation exposure to antimony trioxide.
Several studies of antimony smelter workers show that workers developed
pneumoconiosis, chronic cough, and upper airway inflammation following
chronic exposure to antimony trioxide (McCallum 1963, 1967; Cooper et al.
1968; Potkonjak and Pavlovich 1983). In addition, one study reported
systemic effects following inhalation exposure in smelter workers, including
weight loss, nausea, vomiting, nerve tenderness, and tingling (Renes 1953).
The lungs are also the primary target tissues in
animals following inhalation exposure (see
Table 10–2). All experimental inhalation studies were conducted using
whole-body exposure. Details of particle size and purity are provided in
footnotes. Guinea pigs exposed to antimony trioxide2
(average concentration: 45.4 mg antimony trioxide/m3, 2–3 hr/d, 6
mo) developed pneumonitis, liver and spleen effects, and decreased white
blood cell counts (Dernehl 1945). Similarly, pneumonia was seen following
exposure of rats (100–125 mg antimony trioxide/m3, 100 hr/mo,
14.5 mo) and rabbits (89 mg antimony
developmental effects following inhalation exposure to antimony have been
reported in one human study. Based on an English abstract of a study by
Belyaeva (1967), women working in an antimony plant had a greater incidence
of gynecological problems (not detailed), early interruption of pregnancy,
and spontaneous late abortions compared to women working under similar
conditions who were not exposed to antimony.
As summarized in Reprotox (1999), studies with antimony
compounds other than the trioxide have shown that, although antimony can
enter the fetus (Gerber et al. 1982), antimony compounds are not teratogenic
in chicks (Ridgway and Karnofsky 1952), rats (Rossi et al. 1987), or sheep
(James et al. 1966). However, antimony trichloride (0.1 and 1 mg/dL in
drinking water for 38 d) did decrease pup body weight and had some effects
on cardiovascular responses to noradrenaline, isoprenaline, and
acetylcholine (Rossi et al. 1987).
In summary, based on the weight of evidence, the
subcommittee concluded that there is suggestive evidence that antimony
trioxide is carcinogenic and a quantitative cancer risk assessment was
performed based on the study by Watt (1983)
Although a single oral
gavage of antimony trioxide (400, 666.67, and 1,000 mg/kg) did not cause
chromosome aberrations in mouse bone marrow cells, aberrations were observed
following repeated administration of those doses (Gurnani et al. 1992)
The carcinogenicity of
antimony trioxide by the dermal route of exposure cannot be determined
because of lack of data.
Based on the weight of
evidence (from animal studies), the subcommittee concludes that the data are
suggestive of carcinogenicity following inhalation
indicating that under the worst-case exposure scenario,
antimony trioxide might possibly pose a noncancer risk via inhalation of