Female rat

In laboratory tests, appHcation of DMAC to the skin of pregnant rats has caused fetal deaths when the dosages were close to the lethal dose level for the mother. Embryonal malformations have been observed at dose levels 20% of the lethal dose and higher. However, when male and female rats were exposed to mean DMAC concentrations of 31,101, and 291 ppm for 6 h per day over several weeks, no reproductive effects were observed (6). 

The LD q for sodium bromide taken orally by rats is 3.5 g/kg body weight, and the TD q orally in rats is 720 mg/kg (8). RTECS Hsts data on reproductive effects in male and female rats. Sodium bromide is Hsted in the TSCA Inventory, the Canadian Domestic Substances Hst (DSL), the European Inventory of Existing Commercial Chemical Substances (EINECS), the Japanese Existing and New Chemical Substances (ENCS), and the Korean Existing Chemicals Hst (ECL). It is not regulated by the U.S. Department of Transportation. 

The National Toxicology Program (NTP) reported on tests on mice and rats that there was an increase in the spontaneous incidence of benign tumors in male and female rats and an increase in malignant Hver and lung tumors in B6C3E1 mice. NTP concluded that these data demonstrated clear evidence of carcinogenicity in mice and female rats and some evidence in male rats (35). 

Figure 12.1. Relationship between collagen 8 N values and age of male and female rats raised on controlled diets, and sacrificed at 40 day intervals beginning 91 days after birth.

The LC50 values of methyl parathion have been established in rats. A 1-hour LC50 of 200 mg/m and a 4-hour LC50 of 120 mg/m for males were determined by Kimmerle and Lorke (1968). One-hour LC50 values of 257 mg/m for male rats and 287 mg/m for female rats were determined for 70-80% pure methyl parathion by EPA (1978e) the rats were exposed to aerosols of respirable size. Survivors of toxic doses recovered clinically by 10-14 days postexposure. Sex-related differences in acute mortality of rodents have also been observed after exposure to methyl parathion by other routes (Murphy and Dubois 1958). 

A significant increase in heart-to-body-weight ratio occurred in female rats exposed to 2.5 mg/kg/day methyl parathion in the diet for 2 years, but not in rats exposed to either 0.025 or 0.25 mg/kg/day methyl... 

Male and female rats exposed to 2.5 mg/kg/day methyl parathion in the diet for 2 years had statistically significant reduced body weights when compared to vehicle controls (Suba 1984). This effect was not consistent throughout the study and did not occur in rats exposed to either 0.025 or 0.25 mg/kg/day methyl parathion. Mean food consumption values were significantly elevated in male rats but only within the first 13 weeks of the 2-year exposure to 2.5 mg/kg/day methyl parathion (Suba 1984). Females exposed to 2.5 mg/kg/day methyl parathion had significantly reduced food intake values during the first 2 weeks of exposure, but intake was significantly elevated from week 3 to termination. Effects on food... 

A study of the dermal toxicokinetics of methyl parathion in female rats, sponsored by ATSDR, is being conducted at the University of Mississippi Medical Center. The principal investigator is Dr. Ing K. Ho, Department of Pharmacology and Toxicology, 500 North State Street, Jackson, Mississippi 39216-4505. 

Benke GM, Murphy SD. 1975. The influence of age on the toxicity and metabolism of methyl parathion and parathion in male and female rats. Toxicol Appl Pharmacol 31 254-269. 

Dikshith TSS, Raizada RB, Singh V, et al. 1991. Repeated dermal toxicity of technical HCH and methyl parathion (50EC) to female rats Rattusnorvigicus). Indian J Exp Biol 29 149-155. 

Zhang HX, Sultatos EG. 1991. Biotransformation of the organophosphorus insecticides parathion and methyl parathion in male and female rat livers perfused in situ. Drug Metab Dispos 19 473-477. 

Effects noted in study and corresponding concentrations No adverse effects were observed in the low-dose male and female rats. Mean hemoglobin, hematocrit, and erythrocyte counts were significantly reduced in the high-dose females at 6-24 months of treatment mean hematocrit and erythrocyte counts were significantly reduced in the mid- and high-dose males at 24 months of treatment. 

Irregular respiration was observed in both male and female rats after a 4-hour nose-only inhalation exposure to aerosolized endosulfan (Hoechst 1983a). In both male and female rats, dyspnea was observed at the lowest concentrations tested (12.3 and 3.6 mg/m for males and females, respectively). Autopsies of the rats that died revealed dark-red, pinhead-sized foci on the lungs. It is unclear whether these effects represent direct effects of inhaled endosulfan on respiratory tissues or whether they are secondary to central nervous system effects on respiratory function. No treatment-related effects were... 

Evidence of neurotoxicity was also observed in animal studies. Nose-only exposure of rats to endosulfan at concentrations of 3.6 mg/m in females and 12.3 mg/m in males resulted in trembling and ataxia (Hoechst 1983a). At higher concentrations in both sexes, tremors, tonic-clonic convulsions, and reduced corneal, pupillary, placing, shock, paw-pinch, and cutaneous reflexes were observed. Nose-only exposure of male and female rats to concentrations of endosulfan of up to 2 mg/m for 6 hours/day,... 

In rats, exposed males and females appear to have different sensitivities to the lethal effects of endosulfan exposure. Summary data submitted by Hoechst (1990) showed that female LDjg values ranged between 10 and 23 mg/kg, whereas male LDjo values ranged between 40 and 125 mg/kg. Thus, female rats appear to be 4-5 times more sensitive to the lethal effects of technical-grade endosulfan than male rats. This difference may be related to differences in the toxicokinetics of endosulfan in male and female rats (see also Section 2.3). Insufficient data were available to determine whether differences in sensitivity to lethal effects exist between males and females of species other than the rat. 

Increased mortality was observed in both male rats (at doses of 20.4 mg/kg/day and above) and male mice (at doses of 0.46 mg/kg/day and above) in a 2-year bioassay conducted by the National Cancer Institute (NCI 1978). The authors attributed the excessive mortality in the male rats to treatment-related toxic nephropathy. The high mortality in male mice was possibly due to fighting since no other treatment-related cause for the deaths could be determined. Survival in females of both species was unaffected by endosulfan (NCI 1978). However, survival was significantly decreased in female rats that consumed 5 mg/kg/day for 2 years (FMC 1959b), and in female mice that consumed approximately 2.9 mg technical endosulfan/kg/day for 2 years (Hack et al. 1995 Hoechst 1988b). In these studies, survival in male rats was not affected at 5 mg/kg/day for 2 years (FMC 1959b) and survival in male mice was not affected at 2.51 mg/kg/day for 2 years (Hoechst 1988b). 

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