Hematologic system study

In humans, severe cases of acrylonitrile poisoning have resulted in low grade anemia (Wilson 1944 Wilson et al. 1948), but complete recovery was reported. Chronic occupational exposure to low levels of acrylonitrile has not resulted in detectable effects on the hematological system (Sakurai et al. 1978). In intermediate and chronic studies in animals, decreased red cell count, hemoglobin concentration and hematocyte were observed (Bio/dynamics 1980a, 1980b, 1980c Quast et al. 

Intermediate-Duration Exposure. Because the human studies do not report quantitative information on dose or duration, it is not possible to know with certainty whether the combined inhalation and dermal exposures were of intermediate duration. There are intermediate-duration oral exposure data from animal studies that indicate that the liver and the hematologic systems are affected by heptachlor exposure (Enan et al. 1982 Halacka et al. 1974 Pelican 1971). The liver is probably the more sensitive of the two. No intermediate-duration oral or inhalation MRLs for heptachlor or heptachlor epoxide have been determined because of limitations in the studies, including lack of statistical comparisons, insufficient number of dose levels, no identification of NOAELs, and the description of effects that may be considered adaptive and not adverse. 

Intermediate-Duration Exposure. No studies were located on intermediate-duration exposure to 1,3,5-TNB in humans or animals by any route. Therefore, studies in animals would provide useful information. There were also no studies on intermediate-duration exposure by any route to 1,3-DNB in humans. Studies in laboratory animals following intermediate-duration oral exposure to 1,3-DNB showed that a major target is the hematological system (see Section 2.2.2.2), but other targets include the central nervous system (Cody et al. 1981 Linder et al. 1986) (see Section 2.2.2.4) and the male reproductive system (Cody et al. 1981 Linder et al. 1986) (see Section 2.2.2.5). An intermediate oral MRL was derived for 1,3-DNB based on hematological effects in rats exposed for 12 weeks (Linder et al. 1986) (see Section 2.4). Studies to determine whether adverse effects occur in animals after inhalation or dermal intermediate duration exposure would be useful. 

Several chronic inhalation and oral studies and acute dermal studies in animals are reported in the literature. These studies exposed several species of animals to both soluble and less-soluble nickel compounds. The target organs were found to be the respiratory system for inhalation exposure and the respiratory system, gastrointestinal tract, hematological system, and kidneys for oral exposure at high levels. Reproductive and developmental effects were observed in animals after inhalation exposure and after oral exposure to nickel. Nickel sensitivity and dermatitis were also observed. 

More animal than human data are available from which to determine LOAEL or NOAEL values of benzene hematotoxicity. The data show that animal responses to benzene exposure are variable and may depend on factors such as species, strain, duration of exposure, and whether exposure is intermittent or continuous. Wide variations have also been observed in normal hematological parameters, complicating statistical evaluation. The studies show that benzene exerts toxic effects at all phases of the hematological system, from stem cell depression in the bone marrow, to pancytopenia, to histopathological changes in the bone marrow. The following studies demonstrate these adverse hematological effects in animals. Effects on leukocytes, lymphocytes, and bone marrow are also discussed in Section 2.2.1.3. 

Hematological Effects. Both human and animal studies have shown that benzene exerts toxic effects on various parts of the hematological system. All the major types of blood cells are susceptible (erythrocytes, leukocytes, and platelets). In the less severe cases of toxicity, specific deficiencies occur in individual types of blood elements. A more severe effect occurs when there is hypoplasia of the bone marrow, or hypercellular marrow exhibiting ineffective hematopoiesis so that all types of blood cells are found in reduced numbers. This is known as pancytopenia. A biphasic response (i.e., a hyperplastic effect in addition to destruction of the bone marrow cells) has been observed (Aksoy et al. 1972, 1974 Doskin... 

Chronic-Duration Exposure and Cancer. The primary target for adverse systemic effects of benzene following chronic exposure is the hematological system. Hematological toxicity was reported in studies of humans chronically exposed to benzene in the air in the workplace (Aksoy and Erdem 1978 Aksoy et al. 1971, 1972, 1974, 1987 Cody et al. 1993 Doskin 1971 Erf and Rhoads 1939 Goldwater 1941 Greenburg et al. 1939 Kipen et al. 1989 Li et al. 1994 Townsend et al. 1978 Yin et al. 1987c). 

The hematological system is the primary target for 2-butoxyethanol toxicity. Therefore, further animal studies designed to confirm and extend the data of Dodd et al. (1983) for inhalation exposure, and animal... 

The primary systemic targets of endosulfan toxicity in animals following dermal exposure are the liver and kidney. Adverse hematological effects have also been observed following dermal administration of endosulfan. No studies were located regarding musculoskeletal effects in humans or animals after dermal exposure to endosulfan. 

System This column further defines the systemic effects. These systems include respiratory, cardiovascular, gastrointestinal, hematological, musculoskeletal, hepatic, renal, and dermal/ocular. "other" refers to any systemic effect (e.g. a decrease in body weight) not covered in these systems. In the example of key number 18, one systemic effect (respiratory) was investigated in this study. 

---