REGULATORY TOXICOLOGY AND PHARMACOLOGY 26, 271280 (1997)

ARTICLE NO. RT971155

Hazard Assessment of Boric Acid in Toys

Andre G. Craan,* Anthony W. Myres, and Douglas W. Green
*Product Safety Laboratory and Environmental Substances Division, Environmental Health Directorate,
Health Protection Branch, Health Canada, Ottawa, Ontario, Canada K1A OL2

Received May 21, 1997

Goldbloom and Goldbloom, 1953; Wong et al., 1964).

Boric acid (H3BO3) has been used in a wide variety of
applicationsmedication, pesticides, and household
products. Reports of child poisoning by H3BO3 were
common in the clinical literature before 1975. How-
ever, a decline in its use as a bacteriostatic agent cou-
pled with increased regulatory control has almost
eliminated poisonings by accidental ingestion. Sched-
ule I (Part I, Item 8) of the Hazardous Products Act of
Canada, proclaimed in the late 1960s, followed in the
wake of concerns about accidental poisoning and pro-
hibits its use in toys. Since that time, scientific knowl-
edge has increased and has led to a reevaluation of the
hazard associated with H3BO3 . A maximum tolerated
dose (MTD) was sought for children in the most suscep-
tible age range, with a view to determine a maximum
acceptable concentration (MAC) in toys. The effects of
H3BO3 in a variety of exposure scenarios were evalu-
ated. Precedence was given to clinical data in humans,
particularly children, since there is no suitable animal
model of boric acid intoxication. An extensive search
of the pediatric literature was conducted to find a no-
observed-adverse-effect level (NOAEL) or a lowest-ob-
served-adverse-effect level (LOAEL). An analysis of the
pivotal study to the present assessment resulted in the
application of an uncertainty factor of 100 to account
for variations in sensitivity among children and for
the use of a LOAEL. Based on a pediatric LOAEL of
300 mg/kg body wt, we derived a MTD of 3 mg H3BO3/
kg body wt and a MAC of 9.1 mg H3BO3/g of toy. These
results compared favorably with calculations from
other human and animal NOAELs/LOAELs. q 1997
Academic Press
INTRODUCTION
Among its many uses in medications, cosmetics,
laundry detergents, pesticides, fire retardants, metal
alloys, polymers, and arts and crafts, boric acid (H3BO3)
can be found in the modeling line of toys intended for
children. Such toys are commercially available as well
as home-made. Before 1975, reports of H3BO3 poisoning
in young children were common (Young et al., 1949;
271
However, a decline in its use as a bacteriostatic agent,
coupled with increased regulatory control, has almost
eliminated poisonings by accidental ingestion (Canada,
1993). Given the nature of play with modeling material
containing H3BO3 , dermal exposure is the normal use
situation as toys. There are also legitimate concerns
about oral ingestion as a misuse scenario particularly
in children. However, the toys of concern are not ex-
pected to desintegrate to the point of contaminating
the respiratory space of child with particles of boric
acid and borates. Therefore, only the oral and cuta-
neous routes are deemed relevant to the present paper.
National regulatory agencies remain alert to the po-
tential hazard associated with the presence of boron in
various media, particularly in the form of boric acid.
As an example, drinking water guidelines indicate a
lifetime Health Advisory of 0.6 mg B/liter for the
United States (Cantilli, 1991). This value was calcu-
lated from a reference dose of 0.09 mg B/kg/day, i.e., the
highest dose not thought to be associated with adverse
health effects (ATSDR, 1992). In Canada, however, the
interim maximum acceptable concentration of 5 mg B/
liter is based on available practicable technology for
water treatment (Health Canada, 1996). Furthermore,
an Expert Panel of the American College of Toxicology
concluded in 1983 that boric acid is safe in concentra-
tions lower than or equal to 5% (i.e., 50 mg/g) as a
comestic ingredient for adults (Beyer et al., 1983). Eu-
ropean Union Countries have adopted the same level
for use in talc powder (Locatelli et al., 1987).
In view of the differences in duration and frequency
of exposure, use pattern, and human requirements,
particularly for a utility like drinking water, the pre-
ceding guidelines and regulations cannot be extrapo-
lated to childrens products.
The purpose of the present paper is to find the most
appropriate no-observed-adverse-effect level (NOAEL)
or lowest-observed-adverse-effect level (LOAEL) for
calculating the maximum allowable concentration
(MAC) of H3BO3 in toys, equipment, and other products
destined for children in learning or play. To that end,
a literature search was conducted for appropriate
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272 CRAAN, MYRES, AND GREEN
NOAEL and LOAEL from which a maximum tolerable
dose could be derived. The resulting hazard assessment
provides a rationale for limiting bioavailable boric acid
to a nontoxic level in situations of oral exposure of chil-
dren to toys.
METHODS
Our search of boric acid poisonings extended back to
the 1920s and included the more recent TOXLINE (up
to 1995), MEDLINE (to 1996), TOMES Plus databases
(Hazardous Substances Data Bank and Registry of
Toxic Effects of Chemical Substances, Microdex Vol.
31, January 1997). A classification of human and ani-
mal data on boric acid intoxications allowed the identi-
fication of all major organs and functions affected,
as well as symptoms, lethal doses, NOAELs, and
LOAELs. Whenever unavailable in published reports
and in order to estimate the doses of exposure, weights
of children were taken from international growth
charts (Snyder et al., 1984). Furthermore, except where
specified, test concentrations and doses presented
herein were expressed as those of boric acid. Boron and
borax (Na2B4O7r10H2O) weights used in some original
reports were converted into equivalent weight of H3BO3
according to the formulas:
weight H3BO3 weight B 1 5.72
weight H3BO3 weight Na2B4O7r10H2O 1 0.649.
The converting factor 5.72 is the ratio of the molecu-
lar weight of H3BO3 over the atomic weight of boron,
and 0.649 represents four times the ratio of boric acid
over borax molecular weights.
Maximum tolerated dose (MTD) was calculated by
dividing NOAEL or LOAEL values by an uncertainty
factor. This procedure was carried out according to the
following toxicological practice. An uncertainty factor
of 10 was introduced to account for each one of three
criteria, as applicable,
(a) Interspecies variability in extrapolating from an-
imals to humans,
(b) Variability in susceptibility in the human popu-
lation, and
(c) The use of a LOAEL in the absence of a NOAEL.
The final value of the uncertainty factor varies expo-
nentially with the number of criteria considered. For
example, if none of the criteria are met, the uncertainty
factor is equal to 100, i.e., 1. Therefore, data obtained
from infants and children who show higher sensitivity
to boric acid intoxication, can be extrapolated to accept-
able intake without the use of an uncertainty factor.
However, LOAEL values obtained in healthy adults
are subjected to an uncertainty factor of 100, i.e., 10,
for the protection of hypersensitive children, multiplied
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by 10 for using a LOAEL in the absence of a NOAEL. In
some cases, a default value of less than 10 was justified
either by the degree of patient sensitivity relative to the
general population (Krasovskii, 1976; Calabrese and
Gilbert, 1993) or by an apparent smaller LOAEL to
NOAEL ratio compared to other studies (Dourson and
Stara, 1983).
Finally, the MAC was derived from the MTD by
transformation of the equation commonly used in expo-
sure assessment,
MTD
MAC ,
E
where MAC is the maximum allowable concentration
in mg H3BO3/g toy material, MTD is the maximum
tolerated dose in mg H3BO3/kg body wt, and E is the
estimated exposure to consumer product or toy mate-
rial in g/kg body wt.
HUMAN DATA
All the human data examined concern clinical cases
of poisoning except in three joint reports from two labo-
ratories and a Neonatalogy department, where boric
acid had been administered to volunteers (Jansen et
al., 1984a,b) or to children of consenting parents (Fris-
Hansen et al., 1982).
Table 1 lists acute and subchronic effects of boric acid
in humans following oral and cutaneous exposures. The
main target organs are the gastrointestinal tract, the
skin, and the central nervous system (Giardini and
Cardi, 1970; Martin, 1971; Gordon et al., 1973; Baker
and Bogema, 1986). For each exposure type, data for
children are presented first. As noted since 1945, there
still is no reported case of chronic H3BO3 intoxication
in humans (Frost and Richards, 1945).
Ingestion
Lethal doses vary widely in humans (Potter, 1921;
McNally and Rust, 1928; Wong et al., 1964; Restuccio
et al., 1992; Ishii et al., 1993); they have been estimated
to be as low as 143 mg/kg in adults (Arena and Drew,
1986) and 271 mg/kg in children (Young et al., 1949),
although there are several cases of children and adults
surviving ingestion of amounts similar to or greater
than these doses (Litovitz et al., 1988).
In its strict definition, a true acute NOAEL has not
been found for boric acid in humans. Several dose levels
appear in the literature as provoking no symptoms (Ad-
elhardt and Fogh, 1983; Jansen et al., 1984b). All ex-
cept two of these doses (Giardini and Cardi, 1970; Jan-
sen et al., 1984b) are higher than the lowest reported
LOAEL of 63.2 mg/kg (Table 1). The first of these two
exceptions, a pediatric no-symptom level of 7.9 mg/kg
reported from the same study as the LOAEL of 63.2 mg/
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 MAC FOR BORIC ACID IN TOYS 273
TABLE 1
Exposure Levels and Effects of Boric Acid in Humans

Cases assessed/
Age total reported Exposure Estimated dosea Effects Reference

Acute
3 years 1/3 Oral 130 mg/kg No symptoms following Litovitz et al., 1988
induced vomiting
17 months 1/3 Oral 259324 mg/kg No symptoms following Litovitz et al., 1988
gastric aspiration /
charcoal
18 months 1/13 Oral 7.9 mg/kg No symptoms Giardini and Cardi, 1970
1.7 months 1/13 Oral 63.2 mg/kg LOAEL with vomiting Giardini and Cardi, 1970
5 months 1/1 Oral 300 mg/kg LOAEL with vomiting Martin, 1971
14 months 1/4 Oral 833 mg/kg LOAEL with gastric Linden et al., 1986
lavage
2 years 1/4 Oral 667 mg/kg LOAEL with vomiting Linden et al., 1986
24 days 1/2 Oral 542 mg/kg GI and skin reactions Baker and Bogema, 1986
14 months 1/2 Oral 174 mg/kg Skin reactions Baker and Bogema, 1986
1 week 6/8 Oral 271814 mg/kg LD Young et al., 1949
Infant 6/7 Oral 9381875 mg/kg LD McNally and Rust, 1928
3058 years 6/6 Oral 20 mg/kg No symptoms Jansen et al., 1984b
From 1 year 692/784 Oral 900 mg/kg mean No symptoms Litovitz et al., 1988
to 80 years 1088,800 mg/kg
range
From 1 year 92/784 Oral 3,200 mg/kg mean GI symptoms Litovitz et al., 1988
to 80 years 10055,500 mg/kg
range
28 and 35 years 2/4 Oral 1290 and 5121 mg/kg Vomiting Linden et al., 1986
Adult Oral 143 mg/kg LDLo Arena and Drew, 1986
77 years 1/1 Oral 429 mg/kg LD Ishii et al., 1993
45 years 1/1 Oral 3,733 mg/kg LD Restuccio et al., 1992
66 years 1/1 Oral 417 mg/kg LD Potter, 1921
Adult Dermal 8600 mg/kg LDLo Stockinger, 1981

Multiple dose and subchronic

A few days 1/11 35 days oral 184 mg/kg/day No symptoms Wong et al., 1964
2.5 months 3/7 49 weeks oral 2430 mg/kg/day LOAEL OSullivan and Taylor,
1983
4.5 months 1/2 12 weeks oral 4423 mg/kg total, Seizure Wong et al., 1964
53 mg/kg/day
9 months 1/1 5 weeks oral 1800 mg/kg total, Seizure Gordon et al., 1973
51 mg/kg/day
1 week 5/11 35 days oral 505 mg/kg/day LD Wong et al., 1964
15 days 22/32 45 days dermal 26 mg/kg total, No symptoms Fris-Hansen et al., 1982
56 mg/kg/day
4 months 1/1 3 days dermal 333556 mg/kg total, LD Watson, 1945
(abraded skin) 111185 mg/kg/day
28 years 1/3 2 years oral 500 mg/kg/day Anemia Adelhardt and Fogh,
1983
a
Where unavailable, weights of children were obtained from Snyder et al. (1984) in order to calculate actual doses.

kg (Giardini and Cardi, 1970), could be a more likely
candidate for a NOAEL than the second one, a dose of
20 mg/kg (Table 1). This latter dose may not represent
the highest NOAEL since it was purposely selected to
be as low as possible, with a view to describing the
pharmacokinetics of ingested boric acid in the absence
of any disturbances in the normal functions and metab-
olism of healthy volunteer subjects (Jansen et al.,
1984b).
No symptoms were observed in children who in-
gested H3BO3 doses of 130324 mg/kg; vomiting might
have decreased these doses (Adelhardt and Fogh,
1983). A 2-year old boy recuperated from eating 667
mg/kg body wt of boric acid which caused intermittent
vomiting (Linden et al., 1986).
Boric acid intoxication from multiple-dose and sub-
chronic exposure has occurred much less frequently in
humans than from acute exposure. Ingestion of 505

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274 CRAAN, MYRES, AND GREEN
mg/kg/day for 35 days led to the death of 5 of 11
poisoned newborns after a survival period of only 23
days (Wong et al., 1964). However, no symptoms were
seen in an infant who had ingested 184 mg/kg/day dur-
ing the same period. Ingestion of much lower doses over
a few weeks, affected not only the GI tract but also
central nervous functions. In these cases, young pa-
tients fell into seizures (Gordon et al., 1973). OSullivan
and Taylor (1983) also noted the occurrence of seizures
in their patients and recorded a LOAEL of 23.830.4
mg/kg/day over a period of 49 weeks. An exceptional
2-year exposure to 500 mg/kg/day provoked anemia in
a 28-year old woman (Adelhardt and Fogh, 1983).
Dermal Exposure
Lethal dermal doses have been recorded only when
boric acid powder or cream was applied on abraded
skin or to treat burns (Watson, 1945; Stockinger, 1981).
While no symptoms were seen with doses of 56 mg/
kg/day (Fris-Hansen et al., 1982), representing 1/51/
4 the no-symptom oral subchronic LOAEL reported by
OSullivan and Taylor (1983), a total application of
333556 mg/kg over the short period of 3 days (Watson,
1945) was fatal to a 4-month-old baby (Table 1). Dermal
LDLo (lowest lethal dose) was reported to be 8.6 g/kg in
adults (Stockinger, 1981).
ANIMAL DATA
The animal data focus on reproductive toxicology and
teratology. Several NOAEL values are also reported in
all three major exposure situations, i.e., acute, sub-
chronic, and chronic (Table 2).
Oral Exposure
Acute. The acute oral LD50 of H3BO3 was reported
as 26605136 mg/kg body wt in the rat (Pfeiffer et al.,
1945; Smyth et al., 1969; Weir and Fisher, 1972). The
mouse LD50 fell within that same range (Pfeiffer et al.,
1945). Reproductive NOAELs of 292 mg/kg and 500 mg/
kg were identified in two different rat studies (Dixon et
al., 1976; Linder et al., 1990).
Although Weir and Fisher (1972) observed no death
during a 14-day postdosage observation period of dogs
that were force-fed up to 3980 mg/kg boric acid, an
acute oral LD50 of 17802000 mg/kg was reported else-
where (Von Burg, 1992). The dog NOAEL was 696 mg/
kg (Weir and Fisher, 1972).
Subchronic. In a major study of the B6C3F1 mouse,
subchronic lethal doses greater than 1000 mg/kg/day
were reported (NTP, 1987). More recent experiments
provided approximate subchronic reproductive NOAELs
of 78, 125, and 248 mg/kg/day in pregnant rats, rabbits,
and mice, respectively (Heindel et al., 1992, 1994). The
rat data were later confirmed by the identification of
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an exact NOAEL of 74 mg H3BO3/kg/day (Price et al.,
1995). A dose that was double the rabbit NOAEL
caused 90% prenatal loss in that species (Heindel et
al., 1994; see Table 2). Testicular atrophy was noted in
rats and dogs who had 10 mg/g boric acid in their food
for 90 days (Weir and Fisher, 1972). The dose was esti-
mated to be respectively 1000 mg/kg/day in the rat and
750 mg/kg/day in the dog (Table 2). Such an abnormal-
ity could also be observed in the rat following daily
gavage treatments for a period of 2 weeks (Silaev et
al., 1977).
Chronic. Chronic exposure to boric acid in the diet
(2500 and 5000 ppm) of mice revealed no evidence of
carcinogenicity (NTP, 1987). Testicular degeneration
and sterility occurred in rats fed 6.7 mg/g boric acid in
their diet during 2 years, corresponding to a daily dose
of 334.6 mg/kg body wt (Weir and Fisher, 1972). This
testicular toxicity appears to be the most consistent
adverse effect resulting from long-term exposure of
mice, rats, and dogs (Weir and Fisher, 1972; NTP, 1987;
see Table 2).
Dermal Exposure
Although the measurement of skin exposure to boric
acid may be more easily made in animals than in hu-
mans, the animal data remain scarce. Boric acid was
classified as a mild skin irritant following application
of 5 ml of a 10% solution (500 mg) to both intact and
abraded skin of rabbit and guinea pig (Roubadush et
al., 1965). In a 90-day study, Draize and Kelley (1959)
found no local (absence of primary irritancy) or sys-
temic (absence of secondary irritancy) effects when
doses of 25200 mg/kg/day were applied to the intact
or damaged skin of rabbits (Table 2). The dose of 200
mg/kg/day cannot be considered a true NOAEL since
higher doses were not investigated in this study.
MTD AND MAC
Table 3 lists boric acid intakes acceptable for chil-
dren, i.e., MTD, calculated from various NOAELs and
LOAELs presented in the two preceding tables. Uncer-
tainty factors, indicated in the third column of Table 3,
were selected and applied as described under Methods.
The maximum tolerable dose derived from acute situa-
tions in humans varied from 3 to 13 mg/kg body wt.
Two pediatric studies where exposure to boric acid var-
ied from 3 days to 9 weeks, indicated multiple-dose
LOAELs of 24 and 184 mg/kg/day. MTDs of 2.4 and 1.8
mg/kg/day were calculated from these LOAELs respec-
tively (Table 3).
All MTDs calculated from teratological and acute ex-
posure data in animals fell within the range of that
derived from acute human exposure. The MTD ob-
tained from chronic exposure data of animals was 0.5
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 MAC FOR BORIC ACID IN TOYS 275
TABLE 2
Exposure Levels and Effects of Boric Acid in Animals

Species Exposure Dose Effects and responses Reference

Acute
Mouse Oral 3450 mg/kg LD50 Pfeiffer et al., 1945
Rat Oral 292 mg/kg NOAEL fertility Dixon et al., 1976
Rat Oral 500 mg/kg NOAEL male gonads / no Linder et al., 1990
clinical symptoms
Rat Oral 1000 mg/kg Gonadotoxic, spermiation / Linder et al., 1990
sperm quality affected
Rat Oral 2660 mg/kg LD50 Pfeiffer et al., 1945
Rat Oral 5136 mg/kg LD50 Smyth et al., 1969
Rat Oral 31604080 mg/kg LD50 Weir and Fisher, 1972
Guinea pig Dermal 500 mg total Mild irritant Roubadush et al., 1965
Rabbit Dermal 500 mg total Mild irritant Roubadush et al., 1965
Dog Oral 696 mg/kg NOAEL Weir and Fisher, 1972
Dog Oral 17802000 mg/kg LD50 Von Burg, 1992

Subchronic
Mouse 14 day oral 12,875 mg/kg/day LD20 NTP, 1987
Mouse 14 day oral 20,997 mg/kg/day LD60 NTP, 1987
Mouse pregnant 17 day oral ca. 248 mg/kg/day NOAEL Heindel et al., 1992, 1994
No maternal and teratogenic
effect
Mouse male 90 day oral 1647 mg/kg/day Atrophy of seminiferous tubules NTP, 1987
and LD10
Mouse female 90 day oral 3300 mg/kg/day LD60 NTP, 1987
Mouse male 90 day oral 3300 mg/kg/day LD80 NTP, 1987
Rat 14 day oral 669 mg/kg/day Sterility Weir and Fisher, 1972
Rat 14 day oral 1000 mg/kg/day Testicular atrophy Silaev et al., 1977
Rat pregnant 20 day oral ca. 78 mg/kg/day NOAEL Heindel et al., 1992, 1994
No maternal and teratogenic
effect
Rat pregnant 20 day oral 74 mg/kg/day NOAEL Price et al., 1995
Rat 90 day oral 1000 mg/kg/day Testicular atrophy Weir and Fisher, 1972
Rat 90 day oral 1504 mg/kg/day LD100 Weir and Fisher, 1972
Rat 6 month oral 0.015 mg/kg/day Testicular toxicity Krasovskii et al., 1976
Rabbit 4 day oral 850 mg/kg/day LD100 Draize and Kelley, 1959
Rabbit pregnant 14 day oral 125 mg/kg/day NOAEL Heindel et al., 1994
No maternal and teratogenic
effect
Rabbit pregnant 14 day oral 250 mg/kg/day 90% prenatal loss Heindel et al., 1994
Rabbit 90 day dermal 25200 mg/kg/day No local or systemic effects Draize and Kelley, 1959
Dog 90 day oral 750 mg/kg/day Testicular atrophy Weir and Fisher, 1972

Chronic
Mouse 27 week oral 154 mg/kg/day NOAEL Gonadal function Fail et al., 1991
Mouse male 2 year oral 275 mg/kg/day Testicular atrophy and LD40 NTP, 1987
Mouse male 2 year oral 549 mg/kg/day Testicular atrophy and LD80 NTP, 1987
Rat 2 year oral 335 mg/kg/day Testicular atrophy Weir and Fisher, 1972
Rat Multigeneration oral 100 mg/kga NOAEL gonads Weir and Fisher, 1972
Dog 38 week oral 166 mg/kg/day Testicular atrophy Weir and Fisher, 1972
Dog 2 year oral 50 mg/kg/day NOAEL male gonads Weir and Fisher, 1972
a
Rate of dosing not specified.

1.5 mg/kg/day, i.e., slightly lower than that calculated
from pediatric subchronic NOAEL.
How much boric acid or boron should be acceptable
in a toy? The answer to this question can be derived
from the most pertinent MTD among those listed in
the fourth column in Table 3. It is based on consider-
ation of the accidental (one-mouthful) ingestion of
toy material by a child, which is typical of an acute
situation. We selected the lowest MTD calculated
from an acute pediatric LOAEL (Martin, 1971). The

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276 CRAAN, MYRES, AND GREEN

TABLE 3
Maximum Tolerable Dose (MTD) of Boric Acid in Children, Calculated from Various
Proposed NOAELs and LOAELs

Maximum tolerable
Reported NOAEL and LOAEL Uncertainty dose mg/kg
Investigative method mg/kg body wta factor body wta Reference

Acute human exposure

Pediatric clinic 130 No symptoms with 10 13.0 Litovitz et al., 1988
induced vomiting
Pediatric clinic 7.9 No symptoms 2 4.0 Giardini and Cardi, 1970
Pediatric clinic 63 LOAEL 20 3.2 Giardini and Cardi, 1970
Pediatric clinic 300 LOAEL 100 3.0 Martin, 1971
Pediatric clinic 667 LOAEL 100 6.7 Linden et al., 1986
Pediatric clinic 833 LOAEL 100 8.3 Linden et al., 1986
Retrospective study of all 900 No symptoms 100 9.0 Litovitz et al., 1988
ages
Hospital adult case 1290 No symptoms 100 12.9 Linden et al., 1986
Multiple-dose and subchronic human exposure
Pediatric clinic 184 LOAELb 100 1.8 Wong et al., 1964
Pediatric clinic 24 LOAELb 10 2.4 OSullivan and Taylor, 1983
Animal exposure
Acute reproductive study 292 NOAEL 100 2.9 Dixon et al., 1976
in rat
Acute reproductive study 500 NOAEL 100 5.0 Linder et al., 1990
in rat
Acute study in dog 696 NOAEL 100 7.0 Weir and Fisher, 1972
Teratological study in 125 approximate NOAELb 20 6.3 Heindel et al., 1994
rabbit
Teratological study in rat 248 approximate NOAELb 20 12.4 Heindel et al., 1992, 1994
Teratological study in 78 approximate NOAELb 20 3.9 Heindel et al., 1992, 1994
mouse
Teratological study in rat 74 NOAELb 10 7.4 Price et al., 1995
Multigeneration study in 100 NOAELb 10 10 Weir and Fisher, 1972
rat
Chronic reproductive 154 NOAELb 100 1.5 Fail et al., 1991
study in mouse
Chronic study in dog 50 NOAELb 100 0.5 Weir and Fisher, 1972
a
Where unavailable, weights of children were obtained from Snyder et al. (1984) in order to calculate actual doses.
b
Where indicated, NOAEL, LOAEL, and MTD are expressed as mg/kg/day.

rationale for this choice is given under the Discus-
sion.
Jones and Work (1961) have determined, as also con-
firmed by Watson et al. (1983), that 1- to 3-year-old
children could swallow 0.33 ml liquid per kilogram of
their body weight. In children of 1015 kg, this mouth-
ful corresponds to 35 ml or g of material having a
density of 1.
Given these considerations, the MAC of boric acid in
a toy can be calculated as specified under Methods.
MAC is the quotient of the lowest MTD derived from
the acute pediatric LOAEL of 300 mg/kg body wt. (Ta-
ble III), over the estimated exposure (E), i.e., the vol-
ume or the weight of a swallow per kilogram of body
weight, as
3.0 mg boric acid/kg body wt
0.33 g toy material/kg body wt
9.1 mg boric acid per gram of toy.
This MAC for boric acid corresponds to a boron MAC
of 1.6 mg/g, calculated from the ratio of B atomic weight
over H3BO3 molecular weight (i.e., 9.1 mg/g 1 atomic
weight B/molecular weight H3BO3).
DISCUSSION AND CONCLUSIONS
The available human data summarized in Table 1
can be divided into four sets based on duration (acute
and subchronic) and route of exposure (oral and cuta-
neous). Inhalation data were not listed because such
an exposure is considered an occupational concern (as
in borax mining) rather than a pediatric concern. The
skin exposure data listed were ruled out of the calcula-
tion of a MAC for the following reasons: first, no human
NOAEL or LOAEL were identified for dermal exposure;
second, boric acid may be absorbed through healthy
human skin only in minute quantities which are rap-
idly excreted. Systemic poisoning occurs essentially on

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 MAC FOR BORIC ACID IN TOYS
damaged and abraded skin (Pfeiffer et al., 1945; Draize
and Kelley, 1959). As a result, in the present paper, a
MAC in toys was calculated toward preventing oral
poisonings which could result from foreseeable misuse
by children. Furthermore, inasmuch as boric acid pene-
trates only the abraded or injured skin, this MAC pro-
vides a wider safety margin for exposure of healthy
hands at play than for oral exposure.
Pertinent LOAEL and Uncertainty Factor
As shown in Tables 1 and 3, the closest to a true
human NOAEL that could be identified were no-symp-
tom levels. Although not the lowest of all, the LOAEL
of 300 mg/kg body wt was deemed the most suitable for
the designation of an MTD and a maximum allowable
concentration of boric acid in toys. This LOAEL was
taken from Martins report (1971) of an asymptomatic
H3BO3 poisoning of an otherwise healthy 6.1-kg baby
girl. This 5-month-old child was accidently fed 210 ml
of 8.7 g/liter boric acid solution. She vomited within 1
hr of ingestion but was admitted to the hospital while
her physical examination showed normal findings. De-
toxification was aided by intravenous infusion and lim-
ited peritoneal dialysis. The patient was discharged on
the third day of admission when her urine revealed no
trace of H3BO3 (Martin, 1971).
The calculated MTD of 3.0 mg/kg body wt was
slightly less than that derived from Giardini and
Cardis no-symptom level of 7.9 mg/kg and LOAEL of
63 mg/kg, the lowest reported acute pediatric LOAELs
(Giardini and Cardi, 1970).
The choice of uncertainty factor representing the al-
gebraic link between LOAEL and MTD was dictated
by common rules of toxicological practice enunciated
under Methods. As can be seen in Table 3, two uncer-
tainty criteria were considered for the LOAEL of 300
mg/kg in an apparent normosensitive child and as-
signed a value of 10 each. One criterion accounted for
extrapolation from normosensitive to hypersensitive
individuals. The other was for the use of a LOAEL in
the absence of a NOAEL. In cases (McNally and Rust,
1928; Linden et al., 1986) where an adult no-symptom
level was reported as virtually equivalent to a NOAEL,
we have applied an additional factor of 10 for extrapola-
tion from adults to children.
The report with the no-symptom level of 7.9 mg/kg
and the LOAEL of 63 mg/kg (Giardini and Cardi, 1970),
presented two rare pediatric cases where the uncer-
tainty criterion for sensitivity was assigned a default
value of 2 rather than 10. This explains the uncertainty
factors of 2 and 20, respectively, shown in Table 3. This
latter value includes the factor of 10 for the lack of a
NOAEL. A close look at that report, based on efective
dose, shows that the two patients involved (Fabrizio L.
and Roberto M.) could be seen, similar to 8 others in a
group of 13, more on the side of hypersensitivity than
AID RTP 1155 / 6E14$$$121 12-04-97 17:47:12
277
normosensitivity. As a result, the uncertainty criterion
for sensitivity could correspond to a value closer to 2
than to 10. This illustrates, as shown with other models
(Dourson and Stara, 1983; Renwick, 1991, 1993; Mur-
ray, 1995), that close examination of the data may help
better determine a realistic uncertainty factor and
avoid using an excessive safety margin that would be
provided by the strict assignment of an order of magni-
tude per uncertainty criterion.
In examining the animal data shown in Table 3, one
should not be surprised to recognize an uncertainty
factor of only 10 applied to a NOAEL which is obtained
from teratological studies. This factor is used on ac-
count of interspecies extrapolation from highly sensi-
tive animal fetuses to children. Furthermore, an addi-
tional factor of 2 was considered for rodent studies
where a LOAEL was identified as being close to a
NOAEL (Heindel et al., 1992, 1994; see Table 3).
Having identified a MAC of 9.1 mg H3BO3 for toys,
which was based on acute poisoning, where subchronic
exposure might be a concern, as in periodic sucking
and/or licking, a MAC of about two-thirds of this value
could be adopted. This coefficient represents the ratio
of subchronic MTD over acute MTD (Table 3) and re-
flects the use in both cases, of the same estimated total
exposure (0.33 g toy material per kg body wt repre-
sented in the last part of Results). Pediatric reports of
subchronic intoxications provide, indeed, a MTD of
1.82.4 mg/kg compared to 3.0 calculated above from
the acute poisoning which is pivotal to the present as-
sessment. Although a MAC of 6.2 mg/g ( 23 1 9.1),
based on subchronic exposure, would provide an addi-
tional margin of safety, acute exposure corresponding
to a MAC of 9.1 mg/g, reflects better the foreseeable
accidental scenario that is typical of children at play.
Significance of the Animal Data to Humans
As shown in Table 3, maximum tolerable doses de-
rived for children from animal data do not generally
contrast with those calculated from human cases. Al-
though some of the animal data strongly support our
calculations, their use in hazard assessment must ac-
count for the differences with human responses.
The systemic toxicity of boric acid is reflected in three
major organs and functions: the gastrointestinal tract,
the central nervous system, and reproductive function.
Although its pharmacokinetics and tissue disposition
appear similar in both humans and animals (Ku et al.,
1991), the responses, seen in Tables 1 and 2, differ in
three main respects. Table 4 summarizes these differ-
ences.
First, vomiting contributes to decrease the dose, and
while it is a common reaction in infants who ingest
boric acid, rodents such as rats lack a well-developed
vomiting reflex. Therefore, since more of the ingested
chemical can be made available to target organs in rats
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278 CRAAN, MYRES, AND GREEN

TABLE 4 first target to be hit. Humans react first by vomiting.

Differences between Humans and Animals While it is clearly a toxic effect of boric acid, vomiting
in the Systemic Toxicity of Boric Acid represents also, as indicated above, an opportunistic
defense mechanism that naturally decreases boron
Effects Human Animal
body burden.
Vomiting Yes No in rodents Following subchronic exposure to low doses, neuro-
CNS effects Yes None reported logic symptoms such as seizures, begin to show in hu-
Reproductive effects None reported Yes mans (Gordon et al., 1973; OSullivan and Taylor,
1983). In some cases, as in the longest ever human
exposure, blood dyscrasia appeared as a major feature
(Gordon et al., 1973; Adelhardt and Fogh, 1983). A 28-
than in humans, emphatic consideration of the rat data
year-old woman liked the taste of boric acid-containing
could lead to an overestimation of the toxicity of boric
baby powder and ingested pinches of it up to an approx-
acid toward the human species.
imate daily dose of 500 mg over a 2-year period. She
Second, the reactions of the central nervous system
developed anemia, underwent blood transfusion, and
(CNS) seen in humans have not been reported in ani-
discontinued the practice (Table 1). This unique case
mals (Table 4). In a battery of sensitivomotor tests per-
showed no permanent after-effects (Adelhardt and
formed on rats and mice, boric acid injected intraperito-
Fogh, 1983). The rarity of such cases explains Wileys
neally was found only to antagonize the hypothermic
(1904) difficulty in providing a definite judgement on
effect of reserpine, but had no direct action on central
possible effects of borax and boric acid on blood chemis-
temperature under normal conditions (Pham-Huu-
try and metabolism.
Chahn et al., 1974).
With high doses, nonlethal effects may take place
Third, as animal studies focused mostly on reproduc-
very rapidly and other organs may react to the point
tive functions, no reproductive or teratogenic effects of
of death. This fatal outcome is preceded by metabolic
H3BO3 were reported in humans (Table 4). Unconvinc-
acidosis and renal and cardiac failures (Ishii et al.,
ingly perhaps in view of the lack of mechanistic evi-
1993).
dence, Whorton et al. (1994) offered their study of birth
rate assessment as proof that borates do not cause re-
Mechanism of human response. The earlier vom-
productive effect in humans. For the most part, their
iting response is a reflection of the irritant property of
epidemiological investigation proved that long-term (at
boric acid. Irritation of the mucosa of the upper GI tract
least 7 years) occupational exposure to aerial concen-
initiates the vomiting reflex through afferent pathways
trations of 38 mg/m3 sodium borate dust does not in-
towards a chemoreceptor trigger zone in the medulla
hibit male workers fertility (Whorton et al., 1994). Yet,
oblongata of the brain.
previously published toxicological evaluations and risk
According to mechanisms completely different from
assessments of boric acid are based essentially on ani-
the preceding, the CNS response could be the result of
mal studies of reproductive and developmental toxicity,
direct intracellular or extracellular chemical effects of
particularly those of Weir and Fisher (1972) and those
the product. The much-protected neuron may be imper-
of the NIEHS National Toxicology Program (Heindel
vious to such a big anion as (B4O7)20. As such, tetrabo-
et al., 1992, 1994; Fail et al., 1991). These reports focus
rate has little chance to cross the bloodbrain barrier.
on chronic exposure, for which human data are lacking.
If it did, then it could interfere with the binding of
In contrast, the present hazard assessment is con-
neurotransmitters to receptors located on the external
cerned with foreseeable acute scenarios based on those
side of neuron membranes. On the other hand, if the
already reported by various pediatric clinics (Young et
two most stable borate anions were present in situ, the
al., 1949; Goldbloom and Goldbloom, 1953; Wong et al.,
intracellular route would be more accessible to meta-
1964; Giardini and Cardi, 1970; Martin, 1971; Gordon
borate (BO2)0 than to the bigger, more polar, although
et al., 1973; Baker and Bogema, 1986; Linden et al.,
more prevalent, tetraborate (B4O7)20. Orthoborate
1986). It is, indeed, the first H3BO3 hazard assessment
(BO3)30 hydrolyzes readily in aqueous solutions to form
that is strictly based on human cases and, additionally,
hydroborate anion H2BO30, which is equivalent to the
it evaluates the animal data in a comparative context.
hydrated metaborate.
Disease development. The human data indicate a Contact of boron compounds with the CNS through
gradation in the expression of the systemic toxicity of either pathway appears to be a slow and perhaps diffi-
boric acid, which is not demonstrated in animals. Tar- cult process occurring in vivo. That is why CNS symp-
get organs are affected in a fashion which varies with toms such as seizures are more common in subchronic
the dose, the duration of exposure, and the time after intoxications. It is therefore apparent that, in order for
exposure. They react in a seemingly orderly manner, boric acid to be effective as a neurotoxicant, repeated
particularly at low doses. exposures are essential in view of its short half-life in
In acute intoxication, the gastrointestinal tract is the the organism.

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 MAC FOR BORIC ACID IN TOYS
Finally, high exposure brings, in addition to the bo-
rate effect, an acid load that may offset the acidbase
balance and stimulate tissue metabolism to the point
of renal and/or cardiac failures (Arena, 1986; Ishii et
al., 1993).
Focus on human data. Current knowledge does not
provide a sure explanation for the differences in the
CNS, reproductive, and teratologic effects between hu-
mans and animals. These differences are worth exam-
ining in comparative toxicology; but, although, as
shown in Table 3, the MTDs calculated from acute and
teratological animal NOAELs concord generally with
those derived from human data, animal experimenta-
tion does not appear to provide a mechanistic represen-
tation of human intoxication with boric acid. The lack of
an animal model did not pose a problem to the present
assessment since our calculation of a MAC of boric acid
in toys was based strictly on pediatric cases.
ACKNOWLEDGMENTS
The authors recognize the valuable contributions of Joseph A. Rud-
dick, Roger H. Walker, and Pierre J. Lalonde in the early stages
of this project. Barry H. Thomas and Kathy Hughes reviewed the
manuscript.
REFERENCES1
Adelhardt, M., and Fogh, A. (1983). Is borax dangerous? Enquiries
to a centre for information on poisoning during a period of 12 years.
[English translation from Danish of Borakser det farligt? 12 ars
foresprgsler til giftinformationscentralen] Ugeskr. Laeger. 145,
38083810.
Arena, J. M., and Drew, R. H. (1986). Poisoning: Toxicology, Symp-
toms, Treatments, p. 131. Thomas, Springfield, IL.
ATSDR (1992). Toxicological Profile for Boron and Compounds.
United States Department of Health and Human Services, Agency
for Toxic Substances and Disease Registry, U.S. Public Health
Service, Atlanta, GA.
Baker, M. D., and Bogema, S. C. (1986). Ingestion of boric acid by
infants. Am. J. Emerg. Med. 4, 358361.
Beyer, K. H., Bergfeld, W. F., Bernt, W. O., Boutwell, R. K., Carlton,
W. W., Hoffman, D. K., and Schroeder, A. L. (1983). Expert Panel
of the American College of Toxicology: Final report on the safety
assessment of sodium borate and boric acid. J. Am. Coll. Toxicol.
2, 87125.
Calabrese, E. J., and Gilbert, C. E. (1993). Lack of total independence
of uncertainty factors (UFs): Implications for the size of the total
uncertainty factor. Regul. Toxicol. Pharmacol. 17, 4451.
Canada (1993). Consolidation of the Hazardous Products Act, Sched-
ule I, Part I, Item 8 (f). Department of Health, Ottawa, Canada.
Cantilli, R. (1991). Drinking Water Health Advisory for Boron: Gov-
ernment Reports Announcements & Index (GRA&I). United States
Environmental Protection Agency, Washington, DC.
Dixon, R. L., Lee, I. P., and Sherins, R. J. (1976). Methods to assess
reproductive effects of environmental chemicals: Studies of cad-
mium and boron administered orally. Environ. Health Perspect.
13, 5967.
1
Additional references can be made available upon request.
AID RTP 1155 / 6E14$$$121 12-04-97 17:47:12
279
Dourson, M. L., and Stara, J. F. (1983). Regulatory history and exper-
imental support of uncertainty (safety) factors. Regul. Toxicol.
Pharmacol. 3, 224238.
Draize, J. H., and Kelley, E. A. (1959). The urinary excretion of boric
acid preparations following oral administration and topical appli-
cations to intact and damaged skin of rabbits. Toxicol. Appl. Phar-
macol. 1, 267276.
Fail, P. A., George, J. D., Seely, J. C., Grizzle, T. B., and Heindel,
J. J. (1991). Reproductive toxicity of boric acid in Swiss (CD-1)
Mice: Assessment using the continuous breeding protocol. Fun-
dam. Appl. Toxicol. 17, 225239.
Fris-Hansen, B., Aggerbeck, B., and Jansen, J. A. (1982). Unaffected
blood boron levels in newborn infants treated with a boric acid
ointment. Food Chem. Toxicol. 20, 451454.
Frost, D. V., and Richards, R. K. (1945). The low toxicity in animals
of boric acid as a preservative agent. J. Lab. Clin. Med. 30, 138
144.
Giardini, O., and Cardi, E. (1970). Boric acid poisoning in infants:
Cases observed at the Rome Pediatric Clinic from 1958 to 1968.
[English translation of Lavvelenamento da acido borico nellinfan-
zia: Casi osservati nella Clinica Pediatrica di Roma negli anni
19581968.] Minerva Pediatr. 22, 17231726.
Goldbloom, R. B., and Goldbloom, A. (1953). Boric acid poisoning.
Reports of four cases and a review of 109 cases from the world
literature. J. Pediat. 43, 631643.
Gordon, A. S., Prichard, J. S., and Freedman, M. H. (1973). Seizure
disorders and anemia associated with chronic borax intoxication.
Can. Med. Ass. J. 108, 719724.
Health Canada (1996). Guidelines for Canadian Drinking Water
Quality. (Prepared by the Federal-Provincial Subcommittee on
Drinking Water of the Federal-Provincial Committee on Environ-
mental and Occupational Health, 6th edition). Minister of Supply
and Services, Ottawa, Canada.
Heindel, J. J., Price, C. J., Schwetz, B. A., Field, E. A., Marr, M. C.,
Myers, C. B., Morrissey, R. E., and Schwetz, B. A. (1992). Develop-
mental toxicity of boric acid in mice and rats. Fundam. Appl. Tox-
icol. 18, 266277.
Heindel, J. J., Price, C. J., and Schwetz, B. A. (1994). The develop-
mental toxicity of boric acid in mice, rats, and rabbits. Environ.
Health Perspect. 102(Suppl 7), 107112.
Ishii, Y., Fujizuka, N., Takahashi, T., Shimizu, K., Tuchida, A., Yano,
S., Naruse, T., and Chishiro, T. (1993). A fatal case of boric acid
poisoning. J. Toxicol. Clin. Toxicol. 31, 345352.
Jansen, J. A., Andersen, J., and Schou, J. S. (1984a). Boric acid single
dose pharmacokinetics after intravenous administration to man.
Arch. Toxicol. 55, 6467.
Jansen, J. A., Schou, J. S., and Aggerbeck, B. (1984b). Gastrointesti-
nal absorption and in vitro release of boric acid from water-emulsi-
fying ointments. Food Chem. Toxicol. 22, 4953.
Jones, D. V., and Work, C. E. Volume of a swallow. (1961). Am. J.
Dis. Child. 102, 427.
Krasovskii, G. N. (1976). Extrapolation of experimental data from
animals to man. Environ. Health Perspect. 13, 5158.
Krasovskii, G. N., Varshavskaya, S. P., and Borisov, A. I. (1976).
Toxic and gonadotropic effects of cadmium and boron relative to
standards for these substances in drinking water. Environ. Health
Perspect. 13, 6975.
Ku, W. W., Chapin, R. E., Moseman, R. F., Brink, R. E., Pierce, K. D.,
and Adams, K. Y. (1991). Tissue disposition of boron in male Fi-
scher rats. Toxicol. Appl. Toxicol. 111, 145151.
Linden, C. A., Alan, A. H., Kulig, K. W., and Rumack, B. H. (1986).
Acute ingestion of boric acid. Clin. Toxicol. 24, 260279.
Linder, R. E., Strader, L. F., and Rehnberg, G. L. (1990). Effect of
acute exposure to boric acid on the male reproductive system of
the rat. J. Toxicol. Environ. Health 31, 133146.
rtpa AP: RTP
280 CRAAN, MYRES, AND GREEN
Litovitz, T. L., Klein-Schwartz, W., Oderda, G. M., and Schmitz, B. F.
(1988). Clinical manifestations of toxicity in a series of 784 boric
acid ingestions. Am. J. Emerg. Med. 6, 209213.
Locatelli, C., Minoia, C., Tonini, M., and Manzo, L. (1987). Human
toxicology of boron with special reference to boric acid poisoning.
G. Ital. Med. Lav. 9, 141146.
Martin, G. I. (1971). Asymptomatic boric acid intoxication: Value of
peritoneal dialysis. N.Y. State J. Med. 71, 18421844.
McNally, W. D., and Rust, C. A. (1928). The distribution of boric acid
in human organs in six deaths due to boric acid poisoning. J. Am.
Med. Assoc. 90, 382383.
Murray, F. J. (1995). A human health risk assessment of boron (boric
acid and borax) in drinking water. Regul. Toxicol. Pharmacol. 22,
221230.
National Toxicology Program (NTP). (1987). Toxicology and Carcino-
genesis Studies of Boric Acid (CAS No. 10043-35-3) in B6C3F1 Mice
(Feed Studies). U.S. Department of Health and Human Services,
National Institutes of Health, Technical Report Series No. 324,
NIH Publ. No. 88-2580, Research Triangle Park, NC.
OSullivan, K., and Taylor, M. (1983). Chronic boric acid poisoning
in infants. Arch. Dis. Child. 58, 737749.
Pfeiffer, C. C., Hallman, L. F., and Gersh, I. (1945) Boric acid oint-
ment: A study of possible intoxication in the treatment of burns.
J. Am. Med. Assoc. 128, 266274.
Pham-Huu-Chahn, Sokan, I., and Quessada, M.-H. (1974). Etude
comparative de laction des acides borique, benzene boronique et
p-methyl-benzene boronique sur le systeme nerveux central.
Agressologie 15, 6172.
Potter, C. A case of borax poisoning. (1921). J. Am. Med. Assoc. 76,
378.
Price, C. J., Strong, P. L., Marr, M. C., Myers, C. B., and Murray,
F. J. (1995). Developmental toxicity NOAEL and postnatal recov-
ery in rats fed boric acid during gestation. J. Am. Coll. Toxicol.
14(2), 173. [Abstract P-17]
Renwick, A. G. (1991). Safety factors and establishment of acceptable
daily intakes. Food Add. Contam. 8, 135150.
Renwick, A. G. (1993). A data-derived safety (uncertainty) factor for
the intense sweetener, saccharin. Food Add. Contam. 10, 337
350.
AID RTP 1155 / 6E14$$$121 12-04-97 17:47:12
Restuccio, A., Mortensen, M. E., and Kelley, M. T. (1992). Fatal in-
gestion of boric acid in adult. Am. J. Emerg. Med. 10, 545547.
Roubadush, R. L., Terhaar, C. J., and Fassett, D. W. (1965). Compar-
ative acute effects of some chemicals on the skin of rabbits and
guinea-pigs. Toxicol. Appl. Pharmacol. 7, 559565.
Silaev, A. A., Kasparov, A. A., Korolev, V. V., and Nebstrueva, V. V.
(1977). Electron-microscopic investigation of the effect of boric acid
on the seminiferous tubules of albino rats. Bull. Exp. Biol. Med.
(USSR) 83, 588591.
Smyth, H. F. Jr, Carpenter, C. P., Weil, C. S., Pozzani, U. C., Striegel,
J. A., and Nycum, J. S. (1969). Range-finding toxicity data: List
VII. Am. Ind. Hyg. Assoc. J. 30, 470476.
Snyder, W. S., Cook, M. J., Masset, E. S., Karhausen, L. R., Howells,
G. P., and Tippon, I. H. (1984). Report of the Task Group on Refer-
ence Man. International Commission on Radiological Protection,
pp. 1112. Pergamon, Toronto.
Stockinger, H. E. (1981). The halogens and the nonmetals boron and
silicon. In Pattys Industrial Hygiene and Toxicology (G. D. Clayton
and F. E. Clayton, Eds.), pp. 29373044. Wiley, New York.
Von Burg, R. (1992). Toxicology update: Boron, boric acid, borates
and boron oxide. J. Appl. Toxicol. 12, 149152.
Watson, E. H. (1945). Boric acid: A dangerous drug of little value. J.
Am. Med. Assoc. 129, 332333.
Watson, W. A., Bradford, D. C., and Veltri, J. C. (1983). The volume
of a swallow: Correlation of deglutition with patient and container
parameters. Am. J. Emerg. Med. 3, 278281.
Weir, R. J., and Fisher, R. S. (1972). Toxicologic studies on borax and
boric acid. Toxicol. Appl. Pharmacol. 23, 351364.
Whorton, M. D., Haas, J. L., Trent, L., and Wong, O. (1994). Repro-
ductive effects of sodium borates on male employees: Birth rate
assessment. Occup. Environ. Med. 51, 761767.
Wiley, H. W. (1904). Influence of Food Preservatives and Artificial
Colors on Digestion and Health. I. Boric Acid and Borax, p. 245.
U.S. Department of Agriculture, Government Printing Office, Bul-
letin No. 84, Part I, Washington, DC.
Wong, L. C., Heimbach, M. D., Truscott, D. R., and Duncan, B. D.
(1964). Boric acid poisoning: Report of 11 cases. Can. Med. Assoc.
J. 90, 10181023.
Young, E. G., Smith, R. P., and MacIntosh, O. C. (1949). Boric acid
as a poison. Can. Med. Assoc. J. 61, 447450.
rtpa AP: RTP