Absence of prenatal developmental toxicity from inhaled arsenic trioxide in rats

Abstract

A review of the literature revealed no published inhalational developmental toxicity studies of arsenic performed according to modern regulatory guidelines and with exposure throughout gestation. In the present study, inorganic arsenic, as arsenic trioxide (As(+3), As2O3), was administered via whole-body inhalational exposure to groups of twenty-five Crl:CD(SD)BR female rats for six h per day every day, beginning fourteen days prior to mating and continuing throughout mating and gestation. Exposures were begun prior to mating in order to achieve a biological steady state of As(+3) in the dams prior to embryonal-fetal development. In a preliminary exposure range-finding study, half of the females that had been exposed to arsenic trioxide at 25 mg/m3 died or were euthanized in extremis. In the definitive study, target exposure levels were 0.3, 3.0, and 10.0 mg/m3. Maternal toxicity, which was determined by the occurrence of rales, a decrease in net body weight gain, and a decrease in food intake during pre-mating and gestational exposure, was observed only at the 10 mg/m3 exposure level. Intrauterine parameters (mean numbers of corpora lutea, implantation sites, resorptions and viable fetuses, and mean fetal weights) were unaffected by treatment. No treatment-related malformations or developmental variations were noted at any exposure level. The no-observed-adverse-effect level (NOAEL) for maternal toxicity was 3.0 mg/m3; the NOAEL for developmental toxicity was greater than or equal to 10 mg/m3, 760 times both the time-weighted average threshold limit value (TLV) and the permissible exposure limit (PEL) for humans. Based on the results of this study, we conclude that arsenic trioxide, when administered via whole-body inhalation to pregnant rats, is not a developmental toxicant.

Occupational Hazards and Safety Measures Amongst the Paint Factory Workers in Lagos, Nigeria

“…Increased risk of lung cancer, respiratory irritation, nausea, skin effects, and neurological effects have been reported following inhalation exposure [39]. Human data suggest that dermal or respiratory effects may be the most prevalent [40,41]; respiratory or immunological effects appeared to be the most common following inhalation exposure to inorganic arsenic in animals [42]. In occupational settings, only small amounts of arsenic will be absorbed through the dermal route, so this is usually not a source of concern.…”

“…The mean arsenic urine concentration of 40 μg/L detected in urine samples from paint factory workers was 20 times higher than that found in nonfactory workers (2 μg/L). The urinary excretion of arsenic appears to account for 30–60% of the inhaled dose [42]; this suggests that nearly all arsenic that is deposited in the lung is excreted in the urine. We can thus infer that paint factory workers may be exposed to as high as 20 times more arsenic than the general population.…”

Reversibility of changes in brain cholinergic receptors and acetylcholinesterase activity in rats following early life arsenic exposure

“…Reduction in the body weight following arsenic exposure in the progeny has been observed both in clinical and experimental studies (Holson et al, 1999; Schulz et al, 2002; Saha et al, 2008). Inverse association between environmental arsenic exposure and growth of children has been reported (Saha et al, 2012; Gardner et al, 2013).…”

A review on exposure and effects of arsenic in passerine birds

“…Increased incidences of Raynaud's phenomenon (peripheral vascular disease), vasospasticity, increased systolic blood pressure Humans Jensen and Hansen (1998); Lagerkvist et al (1986) Dermal effects Dermatitis, mild pigmentation, keratosis of skin, or gross pigmentation with hyperkeratinization of exposed skin Humans Cöl et al (1999); Perry et al (1948) Neurological effects Increased in peripheral neuropathy, decreased nerve conduction velocity Humans Feldman et al (1979); Lagerkvist and Zetterlund (1994) Developmental effects Increased incidence of abortion and congenital malformations in children Humans Nordström et al, (1979aNordström et al, ( , 1979b Ocular effects Chemical conjunctivitis Humans Pinto and Mcgill (1953) Cancer Lung cancer Humans Enterline et al, (1987aEnterline et al, ( , 1987b Holson et al (1999); Nagymajtényi et al (1985) Immunological effects Decreased pulmonary bactericidal activity and increased susceptibility to streptococcal infections Mouse Aranyi et al (1985) Gastrointestinal effects Gross gastrointestinal lesions Rat Holson et al (1999) Inhalation exposure (organic arsenic) Respiratory effects Respiratory distress and bright red lungs with dark spots Rat and mouse Stevens et al (1979) Dermal effects Erythematous lesions on feet and ears (probably due to direct irritation from dermal contact with the dust) Rat Stevens et al (1979) Ocular effects Encrustation around the eyes (probably due to direct irritation from ocular contact with the dust)…”