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Description of key information

There no data available on phosphonic ester residue with respect to repeated dose toxicity.
Regarding the individual components of phosphonic ester residue the only available data are provided by Dimethylphosphonate(accounting for about 11 % in phosphonic acid ester residue) by oral and inhalation exposure. The NOAEL (rat ,oral, subchronic exposure) is 100 mg/kg bw/day and the LOAEL(rat, inhalation exposure, subacute) is 12ppm (48.7 mg/m³).

Key value for chemical safety assessment

Additional information

There no data available on phosphonic ester residue with respect to repeated dose toxicity.

Phosphonic ester residue contains monomethyl phosphonate, phosphonic acid, and Dimethylphosphonate, and and salt of pyrophosphoric acid. and phosphate which were not further specified

ORAL APPLICATION

Monomethylphosphonate and phosphonic acid

there are no data available

Dimethylphosphonate - oral application

There is a 2 -year repeated dose toxicity study in male and female F344 rats available in which only mortality, body weight development and tumour development were considered; clinical signs, biochemical or clinical chemical effects were not considered. Based on these limitations, this study was not taken into account with respect to repeated dose toxicity.

In a 13 week gavage study male and female Fischer 344 rats were administered 25, 50, 100, 200, 400 mg/kg bw/day dimethyl phosphonate on 5 days/week within the National Toxicology Program (US Health and Human Services 1985). This study was chosen as key study because it was the most critical study in terms of general toxicology despite the lack of data of hematology, clinical chemistry or urinalysis. The NOAEL was determined 100 mg/kg bw/day for female rats and 200 mg/kg bw/day for male rats based on increased mortality, decreased body weight, eye changes (degeneration of the lens, acute diffuse inflammation of the cornea), increased lung lesions (inflammation, congestion, histiocytosis) and in male rats increased urinary bladder calculi at the highest test dose.

Salt of pyrophosphoric acid and phosphate (not further specified)

There are no data available

INHALATION EXPOSURE

Monomethylphosphonate and phosphonic acid

there are no data available

Dimethylphosphonate

OECD-ICCA_SIDS (published by UNEP 2006) reported that in a 4-week study, male and female Sprague-Dawley rats (20/sex per group) inhaled 48.7, 142.1, 483.1, and 803.9 mg/m3 (12, 35, 119, and 198 ppm) DMP vapor for 6 hours/day on 5 days/week

(Mobil Oil Corporation, 1982).

At all concentrations increased kidney weights were observed in

male and female rats. Irritation of superficial ocular structures, mucosal irritation and keratitis were

shown in all dose groups and in both sexes. The eye changes progressed to cataracts in dose groups

of ≥ 142.1 mg/m3. At ≥ 142.1 mg/m3 cutaneous irritation was observed, the skin effects progressed

to dermatitis at 483.1 mg/m3, and at 803.9 mg/m3 necrosis and acute purulent inflammation of the

skin were main causes of deaths. At 142.1 mg/m3 inflammation of the anterior nares was visible in

male and female rats. At 483.1 mg/m3 the external nares were affected, and at 803.9 mg/m3 red

discoloration of the lungs and the nasal turbinates were observed in both sexes.

In male rats reduced body weight gains were observed at ≥ 142.1 mg/m3. In the next higher dosage

(483.1 mg/m3) body weight losses and increased mortality was shown in male and female rats.

Time to death varied between 7 and 26 days at 483.1 and 803.9 mg/m3. Hypospermatogenesis was

observed in male rats at lethal doses of ≥ 483.1 mg/m3 (details see chapter 3.1.8). Hematopoiesis in

the spleen occurred in 4/18 female rats at 803.9 mg/m3 only and was not observed in the controls or

the lower doses. No historical control data were provided.

The LOAEL derived for this study is 48.7 mg/m3 (12 ppm; corresponds to about 10 mg/kg bw/d).

No NOAEL was achieved in this study

Salt of pyrophosphoric acid and phosphate (not further specified)

There are no data available

DERMAL APPLICATION

There are no data avialble of the individual components of phosphonic ester residue

Justification for classification or non-classification

There no data available on phosphonic ester residue with respect to repeated dose toxicity

ccording to GHS/CLP Regulation 1272/2008 section 3.9.3.4.

Where there is no reliable evidence or test data for the specific mixture itself then the classification of the mixture is based on the cassification of the ingredient substances.

Regarding the available test data results of the ingredient substance Dimethylphophonate, there is no classification required. Therefore no classification/labelling for phosphonic ester residue has to be required.