Octylphosphonic acid

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

None

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

80 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

The key study is GLP compliant with an high quality (Klimisch score = 1)

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

The NOAEL is 80 mg/kg/day, based on the diminution of the percentage of the number of male, but it was considered to be unlikely.

There is no effect on the others parameters observed.

According to the column 1 of REACh Annex IX, a two-generation toxicity study should be performed if the 28-day or 90-day study indicates adverse effects on reproductive organs or tissues. In the present case, in a screening reprotoxicity study available, no toxicologically relevant effects (in absence of parental toxicity) were observed to assume that the registered substance should be considered as reprotoxic regarding the fertility. Therefore it can be considered that there is no datagap concerning the fertility endpoint.

Short description of key information:
Based on the experimental conditions of this study:
The No Observed Adverse Effect Level (NOAEL) for parental toxicity was considered to be 12 mg/kg/day,
The No Observed Effect Level (NOEL) for reproductive performance (mating and fertility) was considered to be 80 mg/kg/day,
The NOAEL for toxic effects on progeny was considered to be 80 mg/kg/day.

Justification for selection of Effect on fertility via oral route:
Only one study available

Effects on developmental toxicity

Description of key information

Based on the experimental conditions of this study: 
The No Observed Adverse Effect Level (NOAEL)for both maternal and embryo fetal development was considered to be 30 mg/kg/day.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

30 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

The key study is GLP compliant with an high quality (Klimisch score = 1)

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

In a GLP OECD 414 compliant study, Octylphosphonic acid was daily administered a suspension in corn oil at dose-levels of 10, 30 or 100 mg/kg/day, from Day 6 to Day 20 p.c., by oral route (gavage), to mated female Sprague‑Dawley rats.

 

At 100 mg/kg/day, non adverse excessive salivation and piloerection were observed. A significantly reduced mean body weight gain was recorded between Days 9 and 12 p.c., and between Days 18 and 21 p.c.. Macroscopic findings were observed on stomach and on kidneys, and net body weight change was decreased when compared with controls. Fetal skeletal variations and malformations were observed.

 

At 30 mg/kg/day, macroscopic findings were observed on kidneys, and non adverse fetal skeletal variations were noted.

 

At 10 mg/kg/day, there were no effects of the test item. At 100 mg/kg/day, in the context of maternal toxicity, the test item treatment was associated with fetal dysmorphogenic potential.

 

Discussion on Fetal skeletal variations

At 100 mg/kg/day, an increased number of litters with fetuses with unossified or incomplete ossification of various part of the skeleton was noted, when compared to controls and Historical Control Data.

From 30 mg/kg/day, there was a dose-related increase in unossified distal phalanx when compared with controls. This was considered to be non adverse test item treatment-related.

These developmental variations were considered to be non adverse test item treatment-related and associated to low thebody weight gain.

 

These findings appear not relevant in the case of human exposure during organogenesis, because the skeletal development at parturition in humans is much more advanced than in rodent species. In conclusion, these findings were not considered as true congenital skeletal malformations, because they were reversible and were therefore considered as variations without any functional consequences.

 

 

Discussion on Fetal skeletal malformations

When compared with controls and Historical Control Data, there were increased fetal and litter incidences of squeletal malformations at 100 mg/kg/day (cervical ribs and absent of thoracic vertebra), and from 30 mg/kg/day (absent ribs). These malformations were considered to be related to the test item treatment and of toxicological importance.

 

At 10 and 30 mg/kg/day and when compared with the control group, there were increased percentages of fetuses and litters with skeletal malformations. However, each individual malformation was not observed at the high dose-level. Therefore, a test item treatment relationship was considered unlikely or of non toxicological significance.

 

No clear evidence on a dose response relationship was highlighted.

 

Conclusion

In absence of maternal toxicity, no teratogenic effects were observed, additionally no clear dose response relationship for fetal skeletal malformations were identified in the study.

Therefore, on the basis of the results obtained in this study, the No Observed Adverse Effect Level (NOAEL) was considered to be 30 mg/kg/day for both maternal parameters and for embryo-fetal development and no classification is retained for the test item.

Justification for classification or non-classification

Based on the available data, octylphosphonic acid is neither classified for fertility nor for developmental toxicity according to the Regulation (EC) No 1272/2008 and the Directive 67/548/EEC.