[Mutagenicity of dichloroacetaldehyde and 2,2-dichloro-1,1-dihydroxy-ethanephosphonic acid methyl ester, possible metabolites of the organophosphate pesticide Trichlorphon]. / Zur Mutagenität von Dichloracetaldehyd und 2,2-Dichlor-1,1-Dihydroxy-athanphosphonsäuremethylester, möglichen Metaboliten des Phosphororganischen Pestizides Trichlorphon.

Dichloroacetaldehyde and 2,2-dichloro-1,1-dihydroxy-ethanephosphonic acid methyl ester which are formed solvolytically from desmethyltrichlorphone, an in vivo metabolite of the organophosphorus pesticide Trichlorphone, show in the dominant lethal test in mice at equimolar dosage (1.6 mmol/kg) a mutagenic activity comparable with that of Trichlorphon. Therefore it cannot be ruled out that the genetic effects of this pesticide may be due in part to the action of its degradation products.

[Differences in right-left distribution of foetuses in uterus cornua and relevance of differentiated germ implantation in uterus? -experiments with laboratory mice (author's transl)]. / Gibt es Unterschiede in der Rechts-Links-Verteilung der Feten in den Uterushörnern der Labormaus - und ist unterschiedliche Plazierung der Keime im Uterus von Bedeutung?

Corpora lutea were counted in laboratory mice, and the production of the right ovary was found to be slightly higher than that of the left. Rates of implantation, consequently, were higher in the right cornu of the uterus. No right-left difference between uterus cornua was observed regarding foetal weight and sex distribution. Any impact of implantation site on germ survival was not safely established.

Effect of dimethoate and O-demethyldimethoate on bone marrow cells of CFLP mice.

The organophosphorus pesticide dimethoate and its nonalkylating O-demethyl derivative were tested for their ability to induce chromosomal alterations in bone marrow cells of CFLP mice after ip administration. A single dose of 20 mg/kg dimethoate proved to be ineffective. However, doses of 60 mg/kg dimethoate or 69 mg/kg O-demethyldimethoate sodium salt significantly increased the aberration rates above those of the controls. The same effect was observed after a nontoxic dose of 690 mg/kg O-demethyldimethoate sodium salt. Considering the distribution of the several aberration types, these findings suggest that the alkylating properties of dimethoate only in part may be responsible for its cytogenetic activity.

[The mutagenicity of desmethyltrichlorphone in dominant lethal test on mice (author's transl)]. / Zur Mutagenität von Desmethyl-Trichlorphon im Dominanten-Letal-Test an der Hausmaus

After i.p. administration to AB mice of 405 mg/kg desmethyltrichlorphone (sodium salt) in a single dose and 54 mg/kg daily for 3 weeks, the mutagenic effect in the dominant lethal test was at least the same as that of trichlorphone. these findings indicate that the genotoxic effect of trichlorphone is not likely to be due to its alkylating properties.

Toxicological investigations in the semiconductor industry: III: Studies on prenatal toxicity caused by waste products from aluminum plasma etching processes.

The prenatal toxic effects of contaminated vacuum pump oil (Sample A) and solid waste products (Samples B and C) originating from aluminum plasma etching processes in semiconductor manufacturing were investigated. Three strains of pregnant mice with different degrees of sensitivity during organogenesis (days 6-15 of gestation) were treated daily with 1000 mglkg b.w. (Sample A), 500 or 750 mg/kg b.w. (Sample B), and 250, 500, or 750 mg/kg b.w. (Sample C). On day 18 of pregnancy, the animals were killed and examined for gross changes, number and weight of live fetuses, as well as the number of postimplantation losses and malformations. Analytical data showed that the investigated wastes contained various halogenated hydrocarbons and inorganic compounds. Sample A revealed no signs of prenatal toxic action. In contrast, administration of Samples B and C caused strong prenatal toxic effects. The number of live fetuses declined in a dose--related manner, and evidence of intrauterine growth retardation was noted in fetuses that survived to day 18. The number of fetuses with malformations (only cleft palates) rose significantly in accordance with the doses and sensitivity of the strains (> 95 % of the fetuses of the most sensitive strain after 750 mg/kg; 85% after 500 mg/kg).

Cytogenetic, genetic, and embryotoxicity studies with dimethyl 2,2,2-trichloro-1-(2,2,2-trichloro-1-hydroxyethoxy)-ethylphosphonat e, a hypothetical impurity in technical grade trichlorfon.

The hemiacetal (CH3O)2P(O)CHOCHOHCCl3)CCl3, a hypothetical contaminant in technical preparations of the organophosphorus pesticide trichlorfon, was tested for cytogenetic, mutagenic, and embryotoxic activity after ip administration to mice of different strains. A single dose of 81 mg/kg (0.2 mmol/kg) caused a significant enhancement in the percentage of chromosome aberrations in bone marrow cells of CFLP mice; a similar effect was induced by an equimolar single dose of chemically pure trichlorfon (51.5 mg/kg). At the same dosage level, the hemiacetal proved to be ineffective in the micronucleus test on fetal blood of DBA and AB Jena/Halle mice. In the dominant lethal mutation assay, a single dose of 81 mg/kg hemiacetal to males resulted in a slight increase in the fetal mortality of DBA mice, whereas AB Jena/Halle mice did not respond under these conditions. Four consecutive doses of 81 mg/kg hemiacetal to pregnant AB Jena/Halle mice at Days 2, 3, 4, and 5 of gestation caused only a very weak embryotoxic effect comparable to that of trichlorfon at equimolar dosage. On the basis of these results the hemiacetal tested may not be considered to represent a potential risk factor in technical grade trichlorfon.

Cytogenetic and embryotoxic effects of bromophos and demethylbromophos.

The organophosphorus pesticide bromophos and the tetramethylammonium and sodium salts of demethylbromophos were tested for cytogenetic and embryotoxic activity on mice of different strains. Single intraperitoneal (ip) doses of 183.0 mg/kg (0.5 mmol/kg) and 73.2 mg/kg (0.2 mmol/kg) bromophos caused a significant enhancement in the percentage of chromosome aberrations in bone marrow cells of CFLP mice; similar effects were produced by a single dose of 0.2 mmol/kg demethylbromophos tetramethylammonium salt and demethylbromophos sodium salt trihydrate, respectively, indicating that the cytogenetic activity of bromophos is not connected with its alkylating properties. After repeated ip or oral administration to pregnant mice of strains AB Jena/Halle and DBA, none of the tested compounds showed a marked influence on the total implantation losses, although in some cases the postimplantation losses were significantly increased.

Investigations on the acute toxic, cytogenetic, and embryotoxic activity of phenyl isocyanate and diethoxyphosphoryl isocyanate.

Phenyl isocyanate (I) and diethoxyphosphoryl isocyanate (II), used as intermediates in organic chemical syntheses, were tested for their acute toxic, cytogenetic, and embryotoxic activity on mice of different strains. The oral LD50 values for male CFLP mice were determined to be 196 mg/kg for I and 4080 mg/kg for II. Single oral doses of 1/40 and 1/20, respectively, of the LD50 of I (4.9 and 9.8 mg/kg) and II (102 and 204 mg/kg) did not cause any significant enhancement in the percentage of chromosome aberrations in bone marrow cells of CFLP mice. After oral administration of 9.8 mg/kg I and 204 mg/kg II to pregnant Halle-AB-Jena and Halle-DBA mice at various days of gestation (4, 7, 11, or 15), none of the compounds tested were embryotoxic.

Investigations of the acute toxic, cytogenetic, and embryotoxic activity of buminafos.

The organophosphorus herbicide buminafos (O,O-dibutyl-(1-butylaminocyclohexyl)-phosphonate) was tested for its acute toxic, cytogenetic, and embryotoxic activity on different strains of mice. The oral LD50 value for male NMRI mice was determined to be 3500 mg/kg. Single oral doses of 175, 1000, and 2000 mg/kg did not cause any significant enhancement in the percentage of chromosome aberrations in bone marrow cells of male NMRI mice. After oral administration of 500 and 1000 mg/kg buminafos to pregnant Halle:DBA and Halle:AB mice at Days 6-15 of gestation no embryotoxic effects were observed. The cytogenetic inactivity of buminafos in the bone marrow chromosome assay corresponds to negative findings in other mutagenicity tests.