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Effects on fertility

Additional information

The NOAEL for effects on reproductive function following oral administration of DTPMP in the rat was 294 mg/kg bw/day for males and 312 mg/kg bw/day for females (Biodynamics, 1979; Reliability 2). This is a one-generation study for both males and females (the treatment of the F0 (adult) animals began on Day 0 of gestation. The guideline requires that it start two oestrus cycles before mating, and for a two-generation study dosing should start during growth and then for two oestrus cycles). However, because there were 2 generations produced the study does go part way to addressing the 2-generation issues. No histopathological changes were apparent in reproductive tissue from male or female rats following gavage administration of 850-900 mg/kg bw /day of the sodium DTPMP for up to 90 days (CTL, 1998; Reliability 1).


Short description of key information:
There is no DTPMP ammonium salt test data for this particular endpoint. However, the category hypothesis is that all the members are various ionised forms of the acid 15827-60-8. In a well conducted (rel.2) pre-GLP one generation reproductive toxicity study (Rel. 2), DTPMP administered via the diet caused no clear treatment-related or statistically significant effects in rats. A NOAEL of 294 mg/kg bw/d for males and 312 mg/kg bw/d in females was therefore concluded. The properties and role of ammonia present in solutions of this salt have been given due consideration. Ammonia has been evaluated in detail at EU level. In the harmonised hazard assessment aqueous ammonia is not classified for reproductive toxicity. Therefore it is considered that ammonia in the substance contributes no additional hazard in respect of this endpoint.

Effects on developmental toxicity

Description of key information
There are no data for ammonium salts of DTPMP. 
In a prenatal developmental toxicity screening study (Monsanto, 1982) mated female Sprague-Dawley rats (25/dose) were dosed by gavage at doses of 500, 1000, 2000 mg/kg bw/day (expressed as active acid). They were dosed on gestation days 6 to 19. Control animals were given 0.9% sodium chloride solution. On day 20 all surviving animals were sacrificed. There were no deaths. The highest dose produced marginal toxic effects in the dams, as evidenced by lower mean body weight gain between gestational days 6 and 20, and soft stools in some animals. No treatment-related lesions were detected at gross necropsy of the dams of any treatment group. There were no statistically significant treatment-related effects on postimplantation loss or fetal weight at any dose. Vertebral anomalies were observed in single fetuses in two litters of the 2000 mg/kg bw/day group and one of the 1000 mg/kg bw/day group. The incidence was not statistically significant, but the rare spontaneous occurrence of this type of malformation and the pattern of incidence was suggestive of a treatment-related effect. Review of these results for the REACH assessment concluded that the effects should not be considered adverse as they were not statistically significant and were only observed in the presence of maternal toxicity. Overall, the NOAEL for maternal toxicity was 1000 mg/kg bw/day, and for developmental toxicity was at least 2000 mg/kg bw/day (active acid).
No teratogenic effects were observed in the one-generation reproductive toxicity study (BioDynamics Inc., 1979) and therefore the NOAEC for developmental toxicity was 3000 ppm.
Due to the limitations of the available data for reproduction and development, a position paper has been prepared to explain why additional testing has not been proposed for the phosphonic acids and their salts, including DTPMP and its sodium salts. This summary is attached to this endpoint summary.
Effect on developmental toxicity: via oral route
Dose descriptor:
NOAEL
2 000 mg/kg bw/day
Additional information

The available reproductive and developmental studies all support the conclusion that DTPMP and its salts do not have an adverse effect on development. The properties and role of ammonia present in solutions of this salt have been given due consideration. Ammonia has been evaluated in detail at EU level. In the harmonised hazard assessment aqueous ammonia is not classified for developmental toxicity. Therefore it is considered that ammonia in the substance contributes no additional hazard in respect of this endpoint.

Justification for classification or non-classification

The available data do not suggest that ammonium salts of DTPMP should be classified for adverse effects on fertility or development.

Additional information