Pharmacological Sciences

Systemic Effects

No studies were located regarding respiratory effects in animals or cardiovascular or musculoskeletal effects in humans or animals after oral exposure to boron.

Information on respiratory, gastrointestinal, hematological, hepatic, renal, and dermal/ocular effects is discussed below. The highest NOAEL values and all reliable LOAEL values for these systemic effects for each species and duration category are recorded in Table 2-2 and plotted in Figure 2-2.

Respiratory Effects. Widespread vascular congestion and hemorrhages in the lungs were reported in one infant who ingested 505 mg boron/kg/day (Wong et al. 1964).

TABLE 2-2. Levels of Significant Exposure to Boron and Compounds - Oral

Exposure _LOAEJ__(effect)_

Key to frequency/ NOAEL Less serious Serious figure3 Species Route duration System (mg/kg/day) (mg/kg/day) (mg/kg/day) Reference Form

ACUTE EXPOSURE Death

505 (increased mortali ty) 550 (LD50)

642 (LD50)

510 (LD50)

898 (LD50)

2251 (increased mortali ty)

Wong et BA

al. 1964

Wei r and BA

Fisher 1972

Smyth et BX

al. 1969

Wei r and BX

Fisher 1972

Smyth et BA

al. 1969

NTP 1987 BA

Wei r and BX

Fisher 1972 Wei r and BA

Fisher 1972

Systemi c 9 Human

Reap

505 (vescular congesti on

Wong et al. 1964

Hepatic

Neurologi cal

Renal

Derm/oc

3-5 d Gastro

Derm/oc

1 d Gastro 14 d Gastro hemorrhage in infantes) 505 (parenchymatous degenerati on, jaundi ce, fatty changes, congestion in i nfants) 765 (parenchymatous degenerati on, reduced uri ne output, protein in urine in i nfants)

505 (extensive shedding of ski n)

184 (vomiting, diarrhea in i nfants)

Wong et al. 1964

505 (erythema, desquamati on in infants)

2251 (gastric hyperplasia and dysplasia)

241 (voniting, di arrhea)

Li nden et al. 1986 NTP 1987

INTERMEDIATE EXPOSURE Death

16 Mouse (F) 13 wk Systemi c

505 (perivascular Wong et BA

hemorrhage, al. 1964

congesti on, thrombosi s, edema i n i nfants)

263 (100% Weir and BX

mortality) Fisher 1972

263 (100% Weir and BA

mortaliy) Fisher 1972

144 (increased NTP 1987 BA

mortali ty

Wei r and BX

Fisher 1972 Settimi et BX al. 1982

23.7 (decreased Seal and BX

body and Weeth 1980

spleen weights) 88 (decreased body Weir and BA

weight) Fisher 1972

Wei r and BA

Fisher 1972

44 (decreased packed Wei r and BX

cell volume and Fisher 1972

hemoglobi n)

Neurologi cal

Developmental

25 Mouse (F) 17 d 43.4 Reproducti ve

Settimi et BX al . 1982

, 6b (reduced 28.4 (rib cage fetal defects, weight) increased resorpti ons) 79 (reduced 175.3 (skeletal fetal effects, body weight) increased resorpti ons)

Heindel et BA al. 1991

Heindel et BA al. 1991

100 (testiculr atrophy, decreased enzymes

26 (partial 88 (complete testicular atorphy atrophy) 50 (reduced testi cular enzymes, reduced testicular and epi di dymal wei ght)

of testes)

Dixon et BX

Fisher 1972

Dixon et al. 1979

CHRONIC EXPOSURE Death

26 (partial 88 (complete testicular atrophy of atrophy) of tests

44.7 (impaired spermatogenesi s)

288 (degeneration atrophy of semi ni ferous tubules)

111 (impaired spermatogenesi s, degeneration of semi ni ferous tubules) 29 (testicular atrophy, spermatogeni c arrest) 44 (severe testicular atrophy) 29 (testicular atrophy, spermatogeni c arrest) 44 (severe testicular atrophy)

Wei r and BX

Fisher 1972

Seal and BX

Weeth 1980 NTP 1987 BA

NIEHS 1990 BA

Wei r and BX

Fisher 1972

Wei r and BX

Fisher 1972 Wei r and BA

Fisher 1972

Wei r and BA

Fisher 1972

mortali ty

NTP 1987

Reproducti ve

58.5 (atrophy Weir and BX

of testes, Fisher 1972

decreased testes wei ght)

58.5 (atrophy Weir and BA

of testes, Fisher 1972

decreased ovulati on) 58.5 (atrophy of Weir and BX

testes, Fisher 1972

decreased ovulati on) 58.5 (atrophy of Weir and BA

seminiferous Fisher 1972

tubule epi theli urn, decreased tubule size, decreased testi cular wei ght)

96 (testicular NTP 1987 BA

atrophy, i ntersti ti al hyperplasi a)

Wei r and BA

Fisher 1972 Wei r and BA

Fisher 1972

aThe number corresponds to entries in Figure 2-2.

bUsed to derive an intermediate oral MRL of 0.01 mg/kg/day; dose divided by an uncertainty factor of 1000 (10

for use of a LOAEL, 10 for extrapolation from animals to humans, and 10 for human variability).

BA = boric acid; BX = borax; (C) = capsule; d = day(s); Derm/oc = dermal/ocular; (F) = feed; Gastro =

gastrointestinal; gen = generation; LD50 = lethal dose, 50% kill; LOAEL = 1owest-observed-adverse-effect level; NOAEL = no-observed-adverse-effect level; Resp = respiratory; (W) = water; wk = week(s); yr = year(s)

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