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Appendices 1-18 to: Report on the Health Effects of Selected Pesticide Coformulants

 3   Human toxicity

3.1   Single dose toxicity

No data were found.

3.2     Repeated dose toxicity

3.2.1     Inhalation

3.2.1.1   Respiratory effects

Inhalation exposure to manganese dusts such as manganese dioxide or manganese tetroxide has lead to an inflammatory response in the lungs mainly of workers exposed to fairly high concentrations (Abdel Hamid et al. 1990, Akbar-Khanzadeh 1993, Kagamimori et al. 1973, Lloyd Davies 1946, Nogowa et al. 1973, Roels et al. 1987a, WHO 1987 – all quoted from ATSDR 2000). 

3.2.1.2   Cardiovascular effects

Three occupational studies indicate that manganese may affect the cardiovascular system following inhalation by lowering the blood pressure. Specific data on exposure levels are lacking. (Saric & Hrustic 1975, Jiang et al. 1996a, Hobbesland et al. 1997b – all quoted from ATSDR 2000).

3.2.1.3   Endocrine effects

Only two studies have measured endocrine effects in humans exposed to inorganic manganese. Foundry workers exposed for approximately 10 years to 0.04-1.1 mg Mn/m³ (particulate matter) and 0.05-0.9 mg Mn/m³ (fumes) had elevated serum prolactin and cortisol levels. (Alessio et al. 1989 – quoted from ATSDR 2000).

Workers from a ferroalloy plant also had elevated serum prolactin levels (Smargiassi & Mutti 1999 – quoted from ATSDR 2000).

3.2.1.4   Neurological effects

From studies of humans exposed to manganese dusts (mainly manganese dioxide) in mines and factories, clear evidence exist that exposure to manganese for longer periods can lead to a series of serious and ultimately disabling neurological effects. This disease, termed manganism, typically begins with feelings of weakness and lethargy typically after several years of exposure but some individuals may begin to show signs after as few as 1-3 months of exposure. As the disease progresses, a number of other neurological signs such as slow and clumsy gait, speech disturbances, a mask like face, and tremors may become manifest. These signs are frequently accompanied by apathy and dullness along with impotence and loss of libido. (Abdel-Hamid et al. 1967, Emera et al. 1971, Mena et al. 1967, Nelson et al. 1993, Rodier 1955, Saric et al. 1977a, Schuler et al. 1957, Shuqin et al. 1992, Smyth et al. 1973, Tanaka & Lieben 1969, Whitlock et al. 1966 – all quoted from ATSDR).Neurological symptoms may improve in some cases (Shuqin et al. 1992, Smyth et al. 1973 – both quoted from ATSDR 2000). However, in most cases the symptoms are irreversible (Cotzias et al. 1968, Huang et al. 1998 – both quoted from ATSDR 2000).

Frequently psychological disturbances such as hallucinations and psychosis emerge (Cook et al. 1974 – quoted from ATSDR 2000). As the disease progresses, patients develop severe hypertonia and muscle rigidity and may be permanently disabled (Rodier 1955 – quoted from ATSDR 2000).

In neurobehavioral tests, people with manganism, generally have significantly poorer eye-hand coordination, hand steadiness, reaction time and postural stability, and a lower level of cognitive flexibility (Chia et al. 1993, 1995, Crump & Rosseau 1999, Iregren 1990, Lucchini et al. 1995, 1999, Mergler et al. 1994, Roels et al. 1987, 1992, 1999, Wennberg et al. 1991 – all quoted from ATSDR 2000).

One occupational study has reported a lack of significant neurological effects (Gibbs et al. 1999 – quoted from ATSDR 2000).

Reliable dose-response data on the inhalation exposure levels leading to neurological injury in humans are not extensive. However, recent epidemiological data indicate that concentrations of manganese in respirable dust in the range of 0.027 to 0.215 mg Mn/m³ and in total dust in the range of 0.14 to 1.59 mg Mn/m³ in the workplace can result in measurable neurological effects. (Roels et al. 1992 – quoted from ATSDR 2000).

People in a Canadian community near a former manganese alloy production plant were exposed to environmental manganese pollution. Both men and women were adversely affected by exposure to manganese as evidenced in performance in neurobehavioral tests and increased neuropsychiatric symptoms. The poorest performance occurred in those with the highest blood manganese level and neurological effects associated with higher levels of blood manganese were more likely to be observed in persons older than 50 years of age. (Baldwin et al. 1999, Beuter et al. 1999, Bowler et al. 1999, Mergler et al. 1999 – all quoted from ATSDR 2000).

3.2.2   Oral intake

3.2.2.1   Neurological effects

Only limited evidence exist that oral exposure to excess manganese in humans leads to neurological effects similar to those reported for inhalation exposure. Although people exposed to excess manganese via food or drinking water for a longer period exhibited neurological symptoms resembling manganism, data were not sufficient in any of the studies to conclude that the symptoms could be attributed solely to manganese exposure. (Banta & Markesbery 1977, Cawte et al. 1987, Goldsmith et al. 1990, He et al. 1994, Holzgraefe et al. 1986, Iwami et al. 1994, Kawamura et al. 1941, Kilburn 1987, Kondakis et al. 1989, Zhang et al. 1995 – all quoted from ATSDR 2000).

Neurological effects in children are described in the chapter on reproductive and developmental effects.

3.2.3   Dermal contact

No data were found.

3.3   Toxicity to reproduction

3.3.1   Inhalation

Decreased libido and impotence are common symptoms in male workers with clinical signs of manganism following exposure to high levels of manganese dusts in the workplace for 1-35 years (Emera et al. 1971, Jing et al. 1996b, Mena et al. 1967, Rodier 1955, Schuler et al. 1957 – all quoted from ATSDR 2000).

In one of the newer studies, the mean total manganese dust concentration was 0.145 mg Mn/m³ as manganese dioxide (Jing et al. 1996b).

The number of children born to occupationally exposed males (inhalation of 0.97 mg Mn/m³ of manganese dust for 1-19 years) was lower than average (Lauwerys et al. 1985 –quoted from ATSDR 2000).

In another occupational study with 70 men, inhalation of manganese dust as manganese dioxide at a median concentration of 0.71 mg Mn/m³ in total dust for an average of 6.2 years had no effect on the fertility (Gennart et al. 1992 – quoted from ATSDR 2000).

One study has reported increased semen liquefaction time, decreased sperm count and decreased sperm viability in workers exposed to manganese dioxide dust at a total concentration of 0.14 –5.5 mg Mn/m³ for one or more years. Workers exposed to manganese fumes at 6.5 – 82.3 mg Mn/m³ for one or more years had decreased sperm viability. However, an increased level of other metals may have influenced the reproductive effect seen. (Wu et al. 1996 – quoted from ATSDR 2000).

The reported reproductive effects may in part occur as a secondary result of neurotoxicity (ATSDR 2000). 

3.3.2   Oral intake

Incidences of stillbirths and malformations have been studied in an Australian aboriginal population living on an island where environmental levels of manganese are high. However, data from a suitable control group are lacking, and the study population is so small that it is not possible to judge if the incidence of developmental abnormalities (and neurological disorders) is higher than average. The route of exposure was assumed to be primarily oral but inhalation exposure was not ruled out. (Kilburn 1987 – quoted from ATSDR 2000).

Two studies in school children showed that increased exposure (at least 0.24 mg Mn/l water for 3 years or more) to manganese in drinking water and food was associated with poorer performance in school and on neurobehavioral tests as compared to children exposed to lower levels (at most 0.04 mg Mn/l water). The children with increased manganese exposure had significantly decreased serum levels of serotonin, noradrenaline, dopamine and acetylcholinesterase. The manganese level of the hair was inversely related to the performance in the neurobehavioral tests. However, the children may have been exposed to other metals that may have influenced the developmental effects seen (He et al. 1994, Zhang et al. 1995 – both quoted from ATSDR 2000).A higher manganese level has also been found in the hair of learning disabled children. The route of excess exposure may be through ingestion of increased amounts, metabolic disturbances, improper balance of other nutrients (such as iron), or decreased ability to clear manganese. (Collipp et al. 1983, Pihl & Parkes 1977 – both quoted from ATSDR 2000).

3.3.3   Dermal contact

No data were found.

3.4   Mutagenic and genotoxic effects

An increase in chromosomal aberrations was found in a group of workers, which had been exposed to a mixture of manganese, nickel, and chromium by inhalation for 10-24 years. The median manganese concentrations during the survey were 0.18 mg Mn/m³ for respirable dust and 0.71 mg Mn/m³ for total dust. No information was available on the genotoxicity of manganese alone. (Elias et al. 1989 – quoted from ATSDR 2000).

3.5   Carcinogenic effects

No data were found.

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