Pursuant to the fulfillment of this need, the National Institute for Occupational Safety and Health (NIOSH) has developed a reporting strategy intended to assist employers In providing personal protection for employees from exposure to carcinogenic, mutagenic, and teratogenic substances. This strategy involves the development of Special Occupational Hazard Reviews which serve to support and complement the other major criteria documentation activities of the Institute. It is the intent of a Special Occupational Hazard Review to document, from a health standpoint, the problems associated with a given industrial chemical or process. While Special Occupational Hazard Reviews are not intended to supplant the more comprehensive NIOSH Criteria Documents nor the less comprehensive NIOSH Current Intelligence Bulletins, they are nevertheless prepared in such a way as to be amenable to full regulatory usage if so desired. Dissemination of Special Occupational Hazard Reviews may be accomplished through appropriate trade associations, unions, industries, and members of the scientific community.#
The acute toxicity of*DDT is relatively low, the estimated oral LD50 in humans being 250 mg/kg. Documented chronic toxicity in humans, clearly related to DDT, is non-existent, and, therefore, the results of experiments with animals must be used to predict chronic effects that may occur in humans. Most notahle of these chronic effects is DDT's potential for producing cancer in animals. DDT has produced an increased incidence of tumors in mice in at least eleven experiments.
Most tumors involved the liver but tumors of the lungs and lymphatic system have also been reported.
In one experiment with mice, DDT induced an increased incidence of tumors at dietary levels as low as 2 and 10 ppm. In two of three experiments involving rats, increased occurrences of liver tumors of varying degrees of malignancy have been reported.
Based on the demonstrated potential of DDT for inducing tumors in both rats and mice, NIOSH recommends that DDT be controlled and handled in the workplace as a suspected occupational carcinogen and that exposure to DDT be minimized to the greatest extent possible. With regard to airborne exposure, NIOSH recommends that the workplace environmental limit be no higher than 0.5 mg/cu m, which is the lowest concentration detectable by the current NIOSH validated sampling and analytical method (NIOSH method S274). Workers should also avoid skin contact with DDT, as the pesticide can be absorbed through the skin.
Percutaneous absorption is substantially increased when DDT is dissolved in organic solvents. The physical and chemical properties of DDT as well as synonyms and trade names are summarized in Table 5.2, and synonyms and trade names are given in the Table 5.3. The structures of DDT, other compounds that occur in technical DDT, and their metabolites are presented in Table 5.1 (WHO 1977). The structure of the o,p' and m,p' compounds can be inferred from those of the p,p' isomers.

# Discovery and Introduction
Technical DDT is synthesized by condensing chloral hydrate with chlorobenzene in the presence of sulfuric acid, a process first discovered by Zeidler in 1874. However, it was 1939 before the insecticidal applications of DDT were identified, by Muller and his coworkers (IARC 1974). By 1943, low-cost production methods had been developed, and commercial production had begun (IARC 1974).

# Changing Patterns of Use and Production
Before 1945, all of the DDT produced in the USA was used or allocated by the military services for various medical and public health uses. Early in 1945 it became available for experimental work in agriculture, and it was commercially available in limited quantitites early in the autumn of the same year. The results were so spectacular that use in the United States increased until 1959, and in response to a demand for exports production continued to increase until about 1963. Even before 1963 some restrictions were placed on its use in the United States, mainly to minimize residues in food and in the feed of animals that produce milk and meat.
Another important factor reducing the use of DDT was the increasing resistance of pests. After a peak in 1959, the use of DDT in the United States declined steadily, except for its major remaining use on cotton (Table 1.3 Outside the United States, DDT is still used extensively for agriculture and vector control in many tropical countries (WHO 1977).
Although many pests of public health importance have become resistant to DDT in some or all of their range, resistance in vectors of malaria has been less widespread (WHO 1977). Accordingly the use of DDT for  The demand for DDT as a residual spray against adult mosquitos in antimalarial programs for the decade 1971-81 has been predicted to be 470,000 metric tons or an average of 47,000 metric tons/year, a figure similar to that predicted for agricultural uses.
The estimated requirements for six regions of the world (Africa, America, Southeast Asia, Europe, the Eastern Mediterranean, and the Western Pacific) are given in Table 1.3.4. The estimated annual demands tend to increase toward a maximum in 1977, with a subsequent decrease until 1981, the last year of the forecast, when the pre dicted requirement is 29,000 metric tons (Goldberg 1975    (1). However, as of 1972, there were reportedly only two major producers left in Europe. DDT is also known to be produced in:
Brazil, where production was 3 million kg in 1969 and is believed to be increasing; Israel, where the total capacity in 1970 was 350 thousand kg; and India, where production for 1971-72 was 4 million kg and was expected to increase. Japan produced 4.6 million kg in 1970 (IARC 1974).

# Exposure
Generally, exposure to DDT is greatest for manufacturers and formulators, moderate for agricultural applicators, less for the general population, and least for special groups whose location or practices minimize their exposure. However, for brief intervals the exposure of agricultural applicators may exceed anything that good industrial practice would permit (WHO 1977).
Occupational exposure to DDT is reflected quantitatively by the concentration of DDT and DDE in blood and fat and by the con centration of DDA in urine (See Section 1.5.4). Urinary excretion of DDA may be increased for several days after a single exposure to DDT by inhalation or percutaneous absorption (Wolfe et al 1970). In a study of formulators, urinary excretion of DDA was increased for only 1 day after exposure (Table 1. (Wolfe andArmstrong 1971, IARC 1974).
Estimates of potential respiratory exposure ranged from 0.11 mg/hr for outdoor spraying to 7.1 mg/hr for indoor spraying ( Similarly, blood levels of DDT and DDE and urinary levels of DDA were 2-10 times higher in aircraft sprayers than those in the general population and increased with the duration of exposure (        (Moriarty 1974(Moriarty , 1975. Thus the data in the literature should be interpreted as describing "quasi-steady" states reached after long-term exposure, and they may underestimate the potential for storage after exposure of more than 1-2 years.
Data for a number of species suggest that residues in tissues increase with increasing dietary concentrations but not in direct proportion to rates of intake (Figures 1.5.7-1.5.9, USDHEW 1969, Hayes 1975, Moriarty 1975). These data have been evaluated and summarized by Hayes (1975) . Additional data for mice are summarized in Table 1.5.4. Storage factors for three species at medium exposure rates (about 1 mg/kg/day or 10 ppm in the diet) are shown in Table 1.5.5. A "storage factor" is defined as the concentration of DDT in the fat of an animal after long-term exposure divided by the concentration in the diet. These storage factors range between 2 and 24. Although data for other species refer only to higher dose ranges, storage factors for dogs, cattle, and hamsters appear to be lower than those for rats and mice in comparable conditions (Figure  (Hayes 1964(Hayes , 1975IARC 1974).
Female rats given DDT at 32 m g A g / d a y secreted about 25% of the

# Mode of Action
The The author suggested that the uncoupling of oxidative phosphorylation in brain mitochondria may be responsible for some phenomena of DDT intoxi cation in mammals.

# Long-Term Feeding Experiments
A number of experiments involving long-term dietary exposure of rats, mice, hamsters, dogs, and other mammals to DDT are summarized in histopathologic changes in the liver, impaired reproduction, and increased incidence of tumors of the liver, lungs, and lympathic system. These effects are summarized in the following sections.
Organ-Specific Toxicity

# Liver and Kidney Effects
In addtion to the effects on the CNS and reproductive organs,
chlorinated

# Morphologic changes (outlined in Table 2.2.1), including an increase in SER
and atypical mitochondria, were observed in all exposed groups and were more pronounced in rats given both DDT and dieldrin.

# Liver Enzyme and Other Biochemical Effects
Numerous studies have been conducted in which DDT has been identified as an inducer of hepatic microsomal enzymes and hence as an effector of the

# Effects on the Cardiovascular System
Most dogs killed by a single dose of DDT die of ventricular fibril lation, and the same is true of some cats, monkeys, and rabbits. Monkeys differ from dogs in that the DDT-sensitized heart is able to recover from fibrillation and resume a normal rhythm (Philips and Gilman 1946). DDT not only sensitizes the myocardium in a way similar to that of halogenated hydrocarbon solvents but, through its action on the central nervous system, produces the stimulus that increases the likelihood of fibrillation.
There is no evidence that repeated, tolerated doses of DDT sensitize the heart. Rats were fed DDT at a dietary level of 200 ppm (about 10 mg/ kg/day) for 8 months, during which they received weekly, intraperitoneal doses of vasopressin, a compound that causes a temporary myocardial ischemia.
Electrocardiograms showed no significant increase in cardiac arrhythmias in the DDT-fed rats as compared with controls. The same results were obtained in rabbits treated in essentially the same way (Jeyaratnam and Forshaw 1974).
Male mice exposed to p,p'-DDE at dietary levels of 125 or 250 ppm throughout life suffered a high incidence of myocardial necrosis (Tomatis et al 1974a).

# Adrenal

# Central Nervous System Effects
The

# In Dogs
In Depending upon the dose regimen of DDT and the particular days injections were given during gestation, the number of implantation sites in the DDT-treated mice was decreased. Subsequent studies by Lundberg (1974) confirmed that DDT caused a decreased in the frequency of implanted embryos.

# In Mice

# Interactions with Steroid

# In Rats
Fifteen male and 15 female Fischer rats were each given 15 mg of DDT (unspecified composition) by stomach tube, 5 times/week, starting at weaning. Exposure lasted 1 year, and survivors were observed for a further 6 months, the average survival being 14 months. No liver tumors were found, and no data were provided on the occurrence of other tumors (Weisburger and Weisburger 1968). Males: controls, 50%; DDT at 250 ppm, 23%; DDT at 500 ppm, 13%;

# Rossi et al (1977) reported that DDT induced liver tumors in
DDT at 1,000 ppm, 0;
Females: controls, 41%; DDT at 250 ppm, 17%; DDT at 500 ppm,0;
DDT at 1,000 ppm, 0.
The occurence of other types of tumors was not reported.

# In Dogs
A total of 22 animals, approximately equally divided by sex, were fed diets containing DDT at 0 (2 dogs), 400 ppm (2 dogs), 2,000 ppm (4 dogs), or 3,200 ppm (14 dogs). Only the control dogs, the two dogs given 400 ppm, and two of the dogs receiving 2,000 ppm survived to the time of sacrifice (39-49 months). Liver damage was reported (Lehman 1965, IARC 1974), but the study was too short to serve as an adequate carinogenicity test.

# Carcinogenic Interactions
As noted in the preceding sections, the actions of DDT and Fischer rats were given daily doses of either 1 mg of 2-AAF or 1 mg of 2-AAF plus 10 mg of DDT, 5 days/week, for 52 weeks, followed by an average of 60 days without exposure. Hepatomas were observed in 90% of the males and 33% of the females in the DDT-exposed groups, versus 67% and 7%, respectively, in the groups exposed to 2-AAF alone.
dieldrin

# Mutagenicity and Related Cytotoxic Effects
Kelly-Garvert and Legator (1973)  Buselmaier et al (1972,1973) (1956,1971).
The first study involved 51 men. Of these, three completed 1 year of dosage at 3.5 mg/man/day, and seven completed 1 year at 35 mg/man/day. Onset in 30-60 min in those most severely affected; men first seen 2-3 hr after ingestion; in spite of severe early vomiting that reduced the effective dose, severity of illness and especially intensity of numbness and paralysis of extremities proportional to amount of DDT ingested; recovery in all but 8 men in 48 hr; 5 others fully recovered in 2 wk, but some weakness and ataxia of the hands in 3 5 weeks after ingestion    exposed to DDT and lindane. However, the workers' exposure to lindane was the only one that was clearly significant, as indicated by its concentration in plasma (Kolmodin-Hedman 1973 ). In a previous study (Kolmodin et al 1969)   In addition to the reported effects listed in

# Effects on Experimental Animals
DOT i n 1*1.

# STORAGE OF DDT'IN THE' TISSUES OF RATS FED DIETS CONTAINING DDT
AT DIFFERENT CONCENTRATIONS FIGURE 1.5.7 (USDHEW 1969).